JP2002517070A - Mass spectrometry with multipole ion guidance. - Google Patents

Abstract

The mass spectrometer (40) is configured with individual multipole ion guides (60, 62) configured in an assembly aligned along a common centerline (5), wherein the mass spectrometer (40) is integrated in the assembly. At least a portion of each configured multiple ion guide (60, 62) is in a vacuum region (72, 73) with a higher background pressure. The multiple ion guides (60, 62) configured in the higher pressure vacuum regions (72, 73) operate in mass-to-charge selection and ion fragmentation modes. Individual sets of RF, +/- DC and resonant frequency waveform voltages supply potential to each multiple ion guide rod to independently control ion propagation actuation, ion trap, mass-to-charge selection and ion fragmentation functions. Enable in ion guidance (60, 62). The presence of a background pressure along the portion of each multi-ion guide linear assembly that is maintained high enough to cause the ions to bombard the neutral gas causes the ions to move from one multi-ion guide to the adjacent ion guide. The directional acceleration allows collision-induced separation (CID) of the ions to be performed, similar to the triple quadrupole ion function.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001] This application is related to US patent application Ser. No. 09 / 235,941, filed Jan. 22, 1999.
6 and PCT / US99 / 01335 filed January 22, 1999, both of which are incorporated by reference in US Provisional Application 6, filed January 23, 1998.
U.S. Provisional Application 60/0 / 072,374, filed May 29, 1998.
Claim priority of 87,246. All priorities of prior applications are claimed and their disclosures are hereby fully incorporated by reference.

FIELD OF THE INVENTION [0002] The present invention relates to the field of mass spectrometric analysis of ions. More specifically, it relates to the construction and operational use of a multi-pole ion guide assembly operating in a high pressure vacuum region.

BACKGROUND OF THE INVENTION [0003] Mass spectrometers (MS) had to be used to solve a number of analytical problems, including solid, gas and liquid phase samples, both in online and offline techniques. Gas chromatography (GC), liquid chromatography (LC
), Capillary electrophoresis (CE) and other solution sample separation systems are connected online to a mass spectrometer configured with various ion source formats. Certain ion source types operate at or near atmospheric pressure, and other ion source types create ions in a vacuum. Mass spectrometers operate in vacuum using different types of mass spectrometers that require different vacuum background pressures for best performance. The present invention includes one or more multipole ion guide configurations configured in the mass spectrometer.
Although the invention can be used with multipole ion guides containing any number of poles, the description of the invention provided below applies primarily to quadrupole or quadrupole ion guide assemblies. Higher mass-to-charge resolution is obtained with quadrupole ion guidance when compared to the performance of ion guides composed of four or more poles. Selective resonance frequency excitation of mass versus charge is also
Easily used by four poles than ion guides with higher numbers of poles. Quadrupole ion guidance is a key element within single and triple quadrupole mass spectrometers and for hybrid mass spectrometers, including time-of-flight, magnetic sector, Fourier transform, and three-dimensional quadrupole ion trap mass spectrometers. Configured as a part. By convention, a quadrupole ion guide operating as a mass-to-charge filter is configured within a background vacuum pressure that minimizes or eliminates ions into a neutral background gas collision. A wider range of background pressures is used when operating the quadrupole in a non-mass versus charge selective RF-only ion propagation mode. In some mass spectrometer devices, quadrupole ion guides operating in RF-only ion propagation mode maintain the background vacuum pressure high enough to collide ion kinetic energy or induce ions to traverse the ion guide length. Separation (CI
D) Constructed in an area that promotes crushing.

[0004] Conventionally, quadrupole mass spectrometers, along with electron multipliers or photodetectors, typically have an analytical mass to charge at background pressure maintained below the 2 × 10 ^-4 Torr range. Operates in select mode. However, the operation of the multipole ion guide is described at an elevated background vacuum pressure with separation of ion mass versus charge. U.S. Patent Nos. 5,401,962 and 5,613,29, which are hereby fully incorporated by reference.
In 4, Ferran describes a small four-array with an electron ionization (EI) ion source and a Faraday cup detector operating as a low mass-to-charge range gas analyzer. This small four array is obtained with a background vacuum pressure as high as 1 × 10 ^-2 torr.
The performance of this short four-array begins to decrease as the background pressure increases to a point where the mean free path of the ions is shorter than the quadrupole length. In US Pat. No. 5,179,278, Douglas describes a quadrupole ion guide configured to send ions from an atmospheric pressure ionization (API) source into a three-dimensional quadrupole ion trap. The quadrupole ion guide described by Douglas in US Pat. No. 5,179,278, which is fully incorporated herein by reference, retains ions before releasing the trapped ions into a three-dimensional quadrupole ion trap. Act as a trap to be done. This 4 in the ion trap
The potential applied to the pole or pole of the polar ion guide is set to limit the range of ion mass to charge released to the ion trap. Quadrupole ion guidance also works with resonant frequency excited collision-induced fragmentation of trapped ions prior to introduction of debris trapped in a three-dimensional ion trap. After the quadrupole ion guide releases its trapped ions to the three-dimensional ion trap, it
It is replenished at the time of three-dimensional ion trap mass spectrometry. A multipole ion guide that extends continuously through a multivacuum pump operation process is described by the White House et al. In US Pat. No. 5,652,427, which is hereby fully incorporated by reference. The portion of the multipole ion guide length is located within the vacuum region with a background pressure greater than 1 millitorr ensuring ions to neutral gas background collisions. In US Pat. No. 5,689,111, which is hereby fully incorporated by reference, Dresch et al.
A hybrid multipole ion guide time-of-flight (TOF) mass spectrometer is described, wherein the multipole ion guide is configured and operative to trap ions, and the trapped ion portion is pulsed by the TOF mass spectrometer. Release into the virtualization area. In U.S. patent application Ser. No. 08 / 694,542, which is hereby fully incorporated by reference, the White House et al. Describe a hybrid mass spectrometer, wherein at least one multipole ion guide is a time-of-flight mass spectrometer. It is composed with.
As described above, the at least one quadrupole ion guide operates in ion propagation, ion trapping, mass-to-charge selection and / or a combination thereof coupled with CID fragmentation mode or time-of-flight mass-to-charge analysis. Hybrid mentioned above
Quadrupole time-of-flight apparatus and method allows implementing the scope of the MS / MS ⁿ function. In an improvement over the prior art, one embodiment of the present invention relates to a mass spectrometer MS
/ MS ⁿ Multiplexes configured and operating within the high pressure vacuum region of a hybrid TOF mass spectrometer that improve performance and exceed the analytical capabilities of the hybrid TOF mass spectrometer
Includes polar ion guidance.

[0005] Multi-ion guides operating in RF-only mode at elevated pressures are used as an effective means to obtain ion kinetic energy attenuation during ion propagation from an atmospheric pressure source to a mass spectrometer. A quadrupole ion guide operating in RF-only mode at background pressures greater than 10 ^-4 Torr and configured to transport ions from an API source to a quadrupole mass spectrometer is hereby incorporated by reference in its entirety. Patent 4,963,736
Described by Douglas et al. Ion collisions with a neutral background gas help to dampen ion kinetic energy during propagation of the ions through the ion guide. Ion collisions with a neutral background gas reduce the diffusion of the primary ion beam kinetic energy and improve the ion propagation efficiency through the ion guide and downstream of the ion guide. The multipole ion guide, operating at elevated background pressure, is a triple quadrupole hybrid magnetic sector and TOF
It has been used as a collision chamber for CID fragmentation in mass spectrometers. A multipolar ion guide configured as a collision cell operates in RF-only mode with a variable DC offset potential applied to all bars. In U.S. Pat. No. 5,847,386, which is hereby fully incorporated by reference, Thomson et al. Create a DC electric field along an ion guide axis to move ions axially through a collision chamber, or an ion guide assembly. By oscillating ions axially back and forth along the length of the body, C
A multipolar ion guide assembly configured to facilitate ID spallation is described. As described above, the ion guide assembly operates in an RF-only mode with an axial electric field and a common RF applied to all poles of the quadrupole ion guide assembly. The multipole ion guide collision chamber integrated into a commercially available mass spectrometer and described in the literature, as a separate ion guide assembly with a common RF added along the multi collision cell pole ion guide length Be composed. In U.S. Pat. No. 4,328,420, which is hereby fully incorporated by reference, French describes a multipolar ion guide configured with an open structure rod assembly. Operating in RF-only mode, these open-structure rod assemblies reduce gas pressure at the analytical quadrupole as a triple quadrupole collision chamber and when connected to corona discharge an atmospheric pressure ion source. It should be configured as a means.
French describes the operation of any mass filter analysis quadrupole in a conventional manner with low vacuum background pressure. In the present invention, at least a portion of the quadrupole ion guide length operating in the mass-to-charge selection mode is configured within a higher background pressure vacuum region where collisions between the ions and the neutral background gas can occur. This configuration of the invention allows for increased performance capabilities and reduced equipment costs, as described below.

A collision cell multipole ion guide configured in a triple quadrupole mass spectrometer is typically surrounded by an enclosure to maintain a locally higher pressure within the collision cell multipole ion guide. The enclosure surrounding the collision cell multipole ion guide is generally located within the lower pressure vacuum region and is configured to minimize the transfer of the higher pressure collision chamber background gas into the surrounding lower vacuum pressure chamber. Is done. A commercially available triple shown as prior art in FIG.
The quadrupole is configured with three multipole ion guides in one vacuum pumping step. The elevated pressure inside the collision chamber is maintained by leaking collision gas into the enclosure surrounding the collision cell multipole ion guide. Gas leaks out of the collision chamber through the entrance and exit openings of the enclosure, which is configured along the triple quadrupole centerline. One embodiment of the invention is a multiple quadrupole located within a common area of higher vacuum pressure configured such that each quadrupole operates in ion mass versus charge selection and / or CID fragmentation mode. This is the configuration of ion guidance. Another embodiment of the present invention is that in the vacuum region of elevated background vacuum pressure, each of the four poles operates in mass-to-charge selection and / or ion fragmentation mode to provide MS / MS ⁿ mass spectrometry functionality. The resulting multiple quadrupole ion guide configuration.

A conventional triple quadrupole mass spectrometer connected to an API source is configured with sufficient vacuum pumping speed in the mass spectrometer vacuum region to prevent or minimize ion collisions with a background gas. Maintain vacuum level. The low pressure vacuum is maintained despite limited gas leakage from the collision chamber and the on source into the chamber. The vacuum pressure in the triple quadrupole collision chamber enclosure is generally maintained at 0.5 to 8 mTorr and the ambient analyzer vacuum chamber pressure is maintained at a low 10 ^-5 to 10 ^-6 Torr range. FIG. 20 shows a conventional triple quadrupole mass spectrometer 550 connected to an atmospheric pressure ion source 560.
FIG. 2 is a configuration diagram of the multipole ion guide of FIG. Individual multipole ion guide assemblies 558,554
, 555 and 556 are aligned along the same central axis in a three-stage vacuum pumping system. Capillary tube 564 provides leakage from atmospheric pressure electrospray ion source 560 into first vacuum pumping step 551. The ions generated in the electrospray source 560 are sent into the vacuum through a supersonic free-jet expansion formed on the vacuum side of the capillary outlet 561. The portion of the ions introduced into the vacuum is
Multipole ion guide 558, hole in electrode 561, multipole ion guide 554, electrode 566
To the detector 565 through a hole in the multipole ion guide 555, a hole in the electrode 567, a hole in the multipole ion guide 556, the electrode 568. Vacuum steps 551, 552 and 5
The pressure in 53 is typically kept below 0.5 to 4 Torr, 1 to 8 mTorr and 1 × 10 ⁻⁵ Torr, respectively, while the pressure inside collision chamber 557 is 0.5 to 8 Torr. Maintained at millitorr. The triple quadrupole is configured to perform MS or single MS / MS continuous mass spectrometry functions. In MS / MS experiments, ions generated at or near atmospheric pressure are subjected to multiple vacuum steps, where low mass or charge selection occurs in the quadrupole 554 with few or no ions for neutral collisions. 553. The selected ions of mass to charge are then accelerated into the elevated pressure region in the collision cell multipole ion guide 555. The resulting population of small ions is directed into the four poles 556 remaining in the low pressure vacuum region 553. The selection of mass versus charge is based on the ion population traversing the quadrupole 556, with small or no ions for neutral collisions, prior to the detection of stationary orbital ions exiting the quadrupole 556 by the ion detector 565. Conveyed to. Four poles 554 are configured with RF-only sections 562 and 568 at their inlet and outlet ends, respectively.
A four pole 556 is also shown at its entry and exit ends, with an RF-only section. In commercially available hybrid quadrupole TOF mass spectrometers, quadrupole 556 is replaced by the TOF mass spectrometer remaining in the fourth vacuum pumping step. Such conventional triple quadrupole and hybrid quadrupole TOF mass spectrometers provide an axial DC acceleration CID
With both ion crushing, only MS and MS / MS mass spectrometry functions can be performed. The selection of mass to charge is conducted into the quadrupole by applying the appropriate RF and DC potentials to the quadrupole, operating near the tip of the first constant region. The invention described below provides the ability to perform MS, MS / MS and MS / MS ⁿ mass spectrometry functions with single or multiple axial DC accelerated CID ion fragmentation or resonant frequency excitation CMS.
Enable with ID ion crushing. The selection of single or multi-valued quadrupole mass-to-charge in the present invention is accomplished by using resonant frequency ion ejection in addition to the quadrupole to create RF and DC
It is obtained by applying an electric potential to a quadrupole or by a combination of both.

As shown in FIG. 20, a conventional triple quadrupole collision chamber is configured inside a vacuum chamber 553. The arrangement of the multiple ion guided collision chamber inside the vacuum chamber, which is maintained at a pressure less than 10 ^-5 Torr, is such that the pumping speed to evacuate the vacuum chamber 553 is sufficient to eliminate gas load leaks from the collision chamber 557. Need that. This additional vacuum pumping burden increases the cost and complexity of the API MS / MS mass spectrometer. One aspect of the invention is to configure multiple quadrupole ion guides within the high pressure vacuum region of the API source using background pressure created by gas leaks from atmospheric pressure to effect CID ion spallation. Mass-to-charge selection and CID ion fragmentation are performed in the first and second vacuum stages of the atmospheric pressure ion source mass spectrometer, necessitating the need for a separate collision chamber with its additional gas further loading the vacuum system. Remove.
The configuration of the API quadrupole and the multiple quadrupole in the high pressure region of the first or second vacuum step of the hybrid mass spectrometer reduces the vacuum pumping speed requirements of the device and its associated costs. Another aspect of the invention is to construct a multi-quadrupole ion guide with significantly reduced pole size from quadrupole assemblies typically found in commercially available triple quadrupole or hybrid quadrupole TOF mass spectrometers. It is to be. The quadrupole or pole diameter decreasing across the center rod spacing (r0) and length minimizes ion propagation time along each quadrupole assembly axis. This increases the analysis speed of the mass spectrometer for a range of mass spectrometry functions. The reduced 4-pole size requires less operating space and power, and reduces the size and cost of the device without compromising performance. Another aspect of the invention is to configure a multiple quadrupole ion guide that extends in a continuous multiple vacuum step to a multiple quadrupole assembly located at least along its length in the high pressure region of the APIMS device. is there. Multiple vacuum pumping step ion guidance is described by the White House et al. In U.S. Patent No. 5,652,427. As described below, configuring a multi-vacuum process quadrupole ion guide with additional quadrupole ion guides within the linear assembly allows a wide range of mass spectrometry functions to be performed with a single mass spectrometer device .

[0009] Bull Baker in US Pat. No. 3,410,997, incorporated herein by reference, and Thomson et al. And James in US Pat. No. 5,847,386 (Proceedings of the 44th Conference on Mass Spectrometry, P. 795). The quadrupole ion guide described by) is composed of sections that apply an RF voltage generated from a single RF supply to all sections of the ion guide assembly or rod set. James describes the operation of the assembly in RF-only ion transport and trap mode. Typically, as described by Bullbaker, AC or RF-only entry and exit sections are within quadrupoles that are set to minimize fringing field effects for ions entering and exiting the quadrupole. Be composed. The RF voltage is typically applied to the entry and exit quadrupole section through capacitive coupling with the primary RF supplied to the center rod section. Offset potential, ie, the common DC applied to all four poles of a given four-pole section
The voltage can be set independently for each section to accelerate the ions within the quadrupole ion guide assembly from one ion guide section to the next. The offset potential applied to the ion guiding section is set to trap ions inside the ion guiding section. In the following discussion, the quadrupole or multipole ion guide assembly includes sections, but all RF voltages applied to each bar in each section start from a common RF supply. In one embodiment of the invention, the different RF feeds connected to the individual quadrupole assemblies are synchronized in frequency and phase to maximize ion transfer efficiency through the multiple quadrupole assembly.

[0010] Electrostatic lenses or electrodes are located between individual multipole ion guides when configuring a multiple ion guide assembly in a mass analyzer. Alternatively, multipole ion guides align end-to-end without an electrostatic lens located between the ion guide assemblies. Electrostatic lenses 561, 566, and 567 serve the dual purpose of minimizing gas conductance between the quadrupole assembly and the decoupling RF or AC voltage applied to adjacent multipole ion guides. The electrodes located between adjacent multipole ion guide assemblies are:
As ions pass from one ion guide assembly to the next, minimizing fringing field effects and minimizing any capacitive coupling between different ion guide sets to avoid thermal frequency distortion of the RF field It is configured to In one embodiment of the present invention, the sides of the junction between two independent, axially aligned, adjacent quadrupole assemblies are sufficiently high to ensure ions against neutral collisions. Within the vacuum pressure maintained. In one embodiment of the invention, the electrostatic lens separating two adjacent multipole ion guide assemblies is replaced with individual RF supplies by independent RF-dedicated quadrupoles. As described below, the high vacuum pressure mutual quadrupole junction and the positioning of the quadrupole lens element between two adjacent quadrupole assemblies are both low when compared to a conventional multiple quadrupole configuration. Increases flexibility in performing mass spectrometry functions at equipment cost.
In one embodiment of the invention, individual quadrupole ion guide assemblies are used to obtain ion mass versus charge selection, CID ion fragmentation and ion trap mass spectrometry functions.
Requires separate RF, +/- DC and supplemental resonance or secu- rary frequency voltage supplies. One aspect of the invention is to construct a multiple quadrupole assembly along a common axis without splitting the electrodes between the two. Each 4 constituted by the invention
The pole assemblies can individually perform mass selection, CID fragmentation, and ion trapping. One or more multi-stage quadrupole assemblies can be configured in a multi-quadrupole assembly according to the invention. Multiple vacuum process multiple ion guidance is disclosed in US Pat. No. 5,652,427,5.
, 89, 111 and U.S. patent application Ser. No. 08 / 694,542, described by the White House and Dresch et al.

In the present invention, separate RF voltage supplies that provide RF voltage to individual multiple ion guide assemblies operate at a common frequency and phase to minimize RF fringing field effects. each
The quadrupole assembly can have different RF amplitudes and / or ion CID breaking operations added during mass to charge selection. Removal of the electrodes between the quadrupole ion guide assemblies increases ion propagation efficiency and directs ions back and forth between the quadrupole ion guide assemblies. Effective two-way transport of ions along the axis of the multiple quadrupole assembly allows a wide range of analytical functions to be run on a single device. As mentioned above, one aspect of the invention is:
Includes an RF quadrupole configured between each analysis quadrupole assembly to minimize any fringing fields or capacitive coupling due to mutual quadrupole differences in RF amplitude, +/- DC voltage and resonant frequency voltage. In another aspect of the invention, the RF-only quadrupole is configured as an RF-only section of each quadrupole assembly that is capacitively coupled to an adjacent quadrupole ion guide RF assembly. In yet another embodiment of the invention, the junction between the individual quadrupole assemblies is in a high pressure vacuum region, such that the junction between the quadrupole assemblies has little or no axial tilt. . Collision of the ions with the background gas helps to attenuate the stationary ion trajectory to the quadrupole centerline, in which case the fringing field effect between the quadrupoles is minimized. This collision damping of the ion trajectory due to the background gas helps to maximize the propagation of ions in the anterior-posterior direction between the individual quadrupole ion guide assemblies. The different, applied RF, DC, and sec-frequency AC fields are between adjacent quadrupoles.

A triple quadrupole, three-dimensional ion trap, hybrid quadrupole TOF, hybrid magnetic sector and Fourier transform (FTMS) mass spectrometer are configured to perform MS / MS analysis. The ion trap and FTMS mass spectrometer are MS / MS ⁿ
Analysis is performed, but ion CID spallation is performed with relatively low energy resonant frequency excitation. CID spallation in triple quadrupoles and in hybrid quadrupole TOF mass spectrometers is obtained by DC acceleration along the quadrupole axis and acceleration of ions into the collision chamber, referred to as CID spallation. Ions are generally accelerated at a few to several tens of eV in quadrupole, DC acceleration, and CID fragmentation. Hybrid or tandem magnetic sector mass spectrometers perform high energy DC accelerated ion spallation with ions that are accelerated into the collision chamber with hundreds or thousands of electron volts. In a conventional triple quadrupole TOF mass spectrometer in which the third quadrupole is replaced by a TOF mass spectrometer in and within a conventional triple quadrupole as shown in FIG. 20, a single charge versus mass Ranges are selected by applying the appropriate RF and +/- DC potentials to the quadrupole within the first analysis quadrupole. The resolution of mass to charge in a quadrupole ion guide operating at low vacuum pressure is limited, in part, by the rapid ion transit time through the quadrupole length. First four
A single mass-to-charge range selected from a continuous ion beam with poles (quadrupole 554 in FIG. 20) accelerates with sufficient energy into a multipole ion guide collision chamber (multipole ion guide 555 in FIG. 20). And CID fracture occurs. Debris ions exiting the collision chamber
Mass analysis is performed by a second analytical quadrupole (4-pole 556 in FIG. 20) or TOF mass spectrometer in a hybrid TOF mass spectrometer. MS / MS analysis functions performed using conventional triple quadrupole and hybrid TOF equipment are limited to a single mass-to-charge range selection step (DC accelerated CID fragmentation with continuous ion beam operation).

[0013] Three-dimensional ion traps operate with single or multiple mass selections for the charge range followed by the ion fragmentation analysis process within the same ion trap volume. Single or multiple MS / MS analysis steps can be performed using the appropriate RF, D,
It is obtained by applying C and resonant frequency emission and an excitation circular AC potential in a stepwise sequence. The space charge of the ions trapped in the three-dimensional ion trap provides performance limitations not encountered in non-trapping with triple quadrupole operation. Both a quadrupole ion guide and a three-dimensional ion trap operating as a mass filter in a triple quadrupole scan mass spectrometer that limits the mass spectral trap rate compared to the non-scanning of a time of flight mass spectrometer . The triple quadrupole works with a continuous ion beam provided by the ion source. Three-dimensional ion traps perform analysis in a batchwise manner, limiting the duty cycle when ions are supplied from a continuous beam ion source. Typically, three-dimensional ion traps operating in RF mode use an additional resonant frequency AC wavelength with the ion trap. The selection of mass to charge is conveyed in triple quadrupole in non-trap mode by adding RF plus +/- DC to quadrupole. The CID ion crushing in the triple quadrupole is performed by DC accelerated crushing. The mass-to-charge selection takes place in the presence of an impinging gas in a three-dimensional ion trap, while the mass-to-charge selection in a triple quadrupole operates with a well-maintained pressure in the vacuum region. , Minimize or eliminate ions to neutral collisions. Multiple multipole ion guides are configured in the present invention in the region of higher background vacuum pressure. Each multipole ion guide can operate in trap mode, mass-to-charge selection mode, and ion fragmentation using RF, +/- DC and applied resonant AC waveforms. In order to detect ions trapped in a three-dimensional ion trap, the ions must enter an unstable trajectory and be ejected through the end cap of the ion trap. Conversely, ions released axially from the end of a multipole ion guide operating in ion trap mode are in a steady trajectory. Thus, while the portion of the ions trapped in the multipole ion guide is released, the ions continue to enter the same ion guide. The ions trapped in the multipole ion guide are free to move along the ion guide axis when using the term two-dimensional trap when referring to traps in the multipole ion guide. As will become apparent from the description of the invention provided below, a two-dimensional ion trap in a multipole ion guide increases the flexibility of the analysis when compared to a three-dimensional ion trap operation. MS / MS ⁿ analysis function is performed by using the resonant frequency excitation or DC acceleration CID crushing, or a combination of both. The invention enables a full range of analytical three-dimensional ion traps and triple quadrupole functions within one range, and renders the implementation of additional mass spectrometry functions unavailable in current mass spectrometry.

In another embodiment of the invention, triple quadrupole analytical functionality, a three-dimensional ion trap and a hybrid quadrupole TOF mass spectrometer are configured in a single device. The invention includes resonance frequency CID ion spallation, DC accelerated CID spallation, but with energies over 100 eV, RF and +/- DC mass to charge selection, single or multiple mass range RF amplitude and resonance frequency ion emission mass to charge It is not limited to choice, even ion traps with quadrupole ion guidance and TOF mass spectrometry. Using the mass spectrometry capabilities described above, a hybrid quadrupole TOF according to the invention can operate in combination with some of the MS / MS ⁿ analysis methods. For example, MS / MS ⁿ (n> 1) is performed using DC accelerated fracturing for each CID step or combination of resonant frequency excitation excitation and DC accelerated CID ion fracturing. Ion traps using mass versus charge selection or CID ion spallation can be implemented without stopping the continuous ion beam in each individual quadrupole assembly. These techniques according to the present invention increase the utilization and sensitivity of the hybrid quadrupole TOF during MS / MS experiments, as described below. Alternatively, MS / MS ⁿ analysis, the trap along with the continuous ion beam into the mass selection and ion crushing step, also can be implemented to talk. A hybrid 4-pole TOF constructed according to the invention is disclosed in US Pat. No. 5,652,427, which is fully incorporated herein by reference;
5,689,111; U.S. patent application Ser. Nos. 08 / 694,542; and 60/021.
, 184, a low cost tabletop device. Emulation and improved performance of prior art API triple quadrupole, three-dimensional ion trap, TO
F, and the hybrid quadrupole TOF mass spectrometer function is obtained by the hybrid quadrupole TOF mass spectrometer of the present invention. The multi-quadrupole ion guide assembly constructed according to the invention can be used in all types of mass spectrometers, tandem and hybrid devices,
And connected to most ion source types that create a gas, liquid or solid phase.

Atmospheric pressure ion sources, including electrospray (ES) and atmospheric pressure chemical ionization (APCI) sources, include single and triple quadrupole ion guides, three-dimensional ion traps, magnetic sectors, Fourier transforms, time of flight, And recently connected to a hybrid quadrupole TOF mass spectrometer. In one aspect of the invention, the combination of the invention can be connected to an atmospheric ion source. In one embodiment of the invention, one embodiment of the invention is configured in a single or triple quadrupole mass spectrometer, or a hybrid three-dimensional ion trap, magnetic sector, Fourier transform, and atmospheric pressure ion source or Configured in a time-of-flight mass spectrometer connected to an ion source that creates ions in a vacuum.

As mentioned above, the invention includes a number of embodiments. Each embodiment includes at least one multipole ion guide operating in a high background pressure vacuum region where multiple collisions between the ions and the neutral background gas occur. Although the invention applies to multipole ion guides having any number of poles, the description primarily refers to quadrupole ion guides. In one embodiment of the invention, the quadrupole ion guide is configured in a vacuum region with background pressure maintained high enough to cause collisional decay of ions across the ion guide length. Each analytical quadrupole ion guide located in the high pressure vacuum region has a trap mode, a single-pass ion propagation mode,
Operate in single or multiple mass-to-charge selection mode and / or resonant frequency CID ion spallation mode with or without a continuous main ion beam. In one embodiment of the invention, high pressure quadrupole ion guidance is achieved by radiating unwanted ions that are traversed or trapped within a quadrupole volume defined by the internal rod radius r0 and rod length. Operate to obtain one or multiple mass to charge range selections. Undesired ion emission is obtained by applying a resonant or specular frequency waveform to the ion quadrupole for a selected period of time with or without RF amplitude cessation. In yet another embodiment of the invention, the ionic, +/- DC potential is:
During the selection of mass versus charge, it acts on the poles of the quadrupole ion guide. +/- DC potential is RF
Acting on the quadrupole or pole while stopping the amplitude and adding the resonant frequency excitation waveform to emit the unwanted, ion mass versus charge value. In another embodiment of the invention, at least one quadrupole ion guide located in the high pressure region and operating in mass-to-charge selection and / or ion CID fragmentation mode is provided as a segmented multipole ion guide. Be composed. The segmented ion guide includes two or more sections that add RF voltage from a common RF voltage supply to all sections. In one embodiment of the invention, at least one section of the quadrupole to be sectioned operates in RF-only mode, while at least one other section operates in mass-to-charge selection and / or ion CID fragmentation mode. . Individual DC offset potentials are added independently to each section to allow trapping of ions or movement of ions from one section to the adjacent section within the segmented quadrupole assembly.

In another embodiment of the invention, the segmented multipole ion guide is configured such that at least one segment extends continuously into a multiple vacuum process. Part of the multi-vacuum process multipole ion guide is a vacuum region where the pressure in the ion guide volume is maintained high enough to introduce multiple ions to neutral collisions as they traverse the ion guide length where the ions are segmented. Located in. The RF voltage acts on all sections of the multi-vacuum process multipole ion guide from a common RF voltage supply. At least one section of the segmented multi-vacuum step multipole ion guide includes an ion trap mode, a single-pass ion propagation mode,
It can be operated in single or multiple mass-to-charge selection mode and / or resonant frequency CID ion spallation mode with or without a continuous main ion beam. In one embodiment of the invention, at least one section of the multi-vacuum pumping step ion guide operates in an RF-only mode, while at least one section operates in a mass-to-charge selection or ion fragmentation mode. The mass-to-charge selection performed in at least one section of the ion guide that is sectioned into multiple vacuum steps may include RF and +/-
Obtained by applying a DC potential to the ion guide pole. Alternatively, undesired ion emission in mass-to-charge selection is obtained by adding a resonant frequency waveform with or without RF amplitude cessation. The range of frequency components required to emit unwanted ion mass to charge values is determined during the ion mass to charge selection process.
By adding a +/- DC voltage to the bar, it decreases with or without a change in RF amplitude. In one embodiment of the invention, the individual offset potentials act on different sections of the multi-vacuum step multipole ion guide. An offset potential is added to the individual ion guide sections to trap ions within the volume defined by surrounding the segmented ion guide poles, or to move ions from one section to the next. The background vacuum pressure along at least one section of the multiple vacuum process ion guide varies along the axial length of the section.

Although the invention is configured with several types of ion sources, embodiments of the invention described herein include, but are not limited to, electrospray, APCI, inductively coupled plasma (ICP), and atmospheric MALDI. Includes a mass spectrometer connected to a non-limiting atmospheric pressure ion source. In the above embodiment, the primary source of background gas in the multipolar ion guide configured in the high pressure vacuum region is from the atmospheric pressure ion source itself. This configuration avoids the need to add additional impingement gas to a separate impingement chamber located within the low pressure vacuum region. Elimination of a separate collision chamber in an API analyzer reduces vacuum pumping speed requirements, equipment size and complexity. The reduction in size and complexity reduces the cost of the mass spectrometer without reducing performance or analytical capabilities. As will be apparent from the following description, a mass spectrometer constructed and operative in accordance with the invention has increased performance and analytical range compared to a triple quadrupole, three-dimensional ion trap and hybrid quadrupole TOF mass spectrometer. Have.

In another embodiment of the invention, the individual multipole ion guide assemblies are configured along a common centerline where the junction between the two is within the high pressure vacuum region. Ion collisions with the background gas on both sides of the junction between two axially adjacent multipole ion guides,
It helps to attenuate the stationary ion radius trajectory toward the centerline which minimizes the fringing field. The forward and backward ion propagation efficiency between the multipole ion guides is maximized by minimizing the fringing field effect at the junction between the two multipole ion guides. The electrostatic lens may or may not be located between the assemblies.

In another embodiment of the invention, the electrode comprises two adjacent four electrodes along a common quadrupole axis.
Not configured for polar ion guidance. Two adjacent quadrupole assemblies constructed according to the invention have the same radial cross-sectional pole dimensions, and the pole elements are axially aligned at the junction between the two quadrupole ion guides. Each 4-pole assembly has an independent set of RF, resonant frequency, +/- DC and offset voltage supplies. In another aspect of the invention, a common RF frequency and phase and a common DC polarity are maintained on adjacent and axially aligned, adjacent and axially aligned poles of a quadrupole ion guide. The RF amplitude, resonant frequency waveform, +/- DC amplitude, and DC offset potential on adjacent quadrupole ion guide poles are adjusted independently for each quadrupole ion guide assembly. Adjusting the relative DC offset potential allows ions with a steady trajectory to move back and forth between two adjacent quadrupoles with minimal propagation field effect and high propagation efficiency. In another embodiment of the invention, at least one segmented quadrupole ion guide assembly is assembled in axial alignment with another quadrupole ion guide assembly, wherein two quadrupole ion guide assemblies are assembled. The junction between the polar ion guide assemblies is located in the region of high background pressure. The junction between adjacent quadrupole ion guides may or may not be configured with secondary electrodes. Alternatively, the junction between two adjacent quadrupole assemblies is configured with an axially aligned quadrupole assembly operating in RF only mode. RF and DC potentials are supplied to this junction quadrupole assembly from a power supply independent of the power supply of two adjacent quadrupole assemblies. In another embodiment of the invention, at least one quadrupole ion guide extending continuously to the multiple vacuum pumping step is configured in axial alignment adjacent to another quadrupole ion guide assembly. In another aspect of the invention, at least one section of the at least one quadrupole operates in mass-to-charge selection and / or CID ion fragmentation mode in the axially aligned quadrupole combination described above. Selected ions of mass to charge across one quadrupole are accelerated from one quadrupole to the adjacent quadrupole by an offset voltage amplitude difference sufficient to effect CID ion spallation. Background gas in the region of the junction between two adjacent quadrupole ion guides serves as collision gas for axially accelerated ions from one quadrupole ion guide to the next. Anterior-posterior ion acceleration with a sufficient offset voltage amplitude difference provided between the quadrupole assemblies is used for debris ions by DC accelerated collision induced separation.

[0021] At least one section of each quadrupole ion guide configured in a multi-quadrupole axially aligned assembly may include an ion trap or single pass ion propagation mode, single or multiple, mass to charge selection. Mode and resonant frequency CID configured to operate in ion fragmentation mode. MS / MS ⁿ analysis function can be obtained by running the selection of related to the mass-to-charge the DC acceleration CID ions crushing. DC accelerated fracturing is obtained by accelerating the mass of charged ions in the forward and backward directions between adjacent ion guides. Alternatively, the ions are fragmented using resonant frequency excited CID ion fragmentation in a volume defined within a section within at least one ion guide configured in a set of four poles. The combination of mass-to-charge selection with DC acceleration and resonant frequency excited CID fragmentation runs in an axially aligned multi-quadrupole ion guide assembly configured in a high vacuum pressure region to provide a wide range of MS / MS ⁿ analysis capabilities Can be obtained. In one embodiment of the invention, the last mass spectrometry step in the MS / MS ⁿ analysis sequence is
Performed using a quadrupole mass spectrometer. The dual quadrupole ion guide assembly is configured as part of a triple quadrupole mass spectrometer according to the present invention. Alternatively, three quadrupole ion guide assemblies surround all triple quadrupole mass spectrometers MS and MS / MS, which, according to the invention, operate with a continuous ion beam supplied from an atmospheric pressure ion source. Be composed.

In another embodiment of the invention, a multi-quadrupole ion guide axial alignment assembly (
At least one connection point between two adjacent ion guides is located in the high-pressure vacuum region) is configured with a TOF mass spectrometer. At least one quadrupole ion guide in the multiple quadrupole assembly is configured to operate in a mass to charge selection and / or CID ion fragmentation mode. In one aspect of the invention, a TOF mass spectrometer is configured and operable to perform mass spectrometry of product ions formed at any step of the MS / MS ⁿ analysis sequence. Single-step MS / MS analysis is obtained by first performing a mass-to-charge analysis step and then performing an ion fragmentation step in a multi-quadrupole ion guide assembly constructed in accordance with the invention with resonant frequency excitation or DC accelerated CID. Analysis of the generated MS / MS generated mass versus charge value ions is performed in a time of filter mass spectrometer. The mass-to-charge selection and ion fragmentation steps in the MS / MS analysis, with or without the primary coil ion trap in the beam,
And done without stopping it. MS / MS ⁿ analysis (n> 1) is obtained by performing a continuous mass-to-charge selection and ion fragmentation step using a multiple quadrupole ion guide assembly constructed according to the invention. The different methods for performing mass-to-charge selection and ion fragmentation are combined into a given MS / MS ⁿ sequence, where the last mass-to-charge analysis step or any provisional mass analysis step is performed. Is TOF
This is performed using a mass spectrometer. In one embodiment of the invention, the API source is connected to a multiple quadrupole TOF hybrid mass spectrometer constructed according to the invention.

In another embodiment of the invention, the segmented ion assembly (at least one compartment)
Minutes extend continuously in a multiple vacuum pumping process) with a TOF mass spectrometer
Be composed. Multi-vacuum pumping process segmented multipole ion guide at least one
Classification includes selection of ion mass versus charge and CID fragmentation, along with ion trapping.
, Or without. In one embodiment of the invention, at least
One multi-vacuum process segmented quadrupole ion guide is configured with a TOF mass spectrometer
Included in a multi-quadrupole ion guide assembly. MS / MSⁿOne or more analysis functions
The selection of ion mass versus charge and the CID fragmentation step
Before performing mass-to-charge analysis of the product ion population using the
In the guide assembly. In one embodiment of the invention, 4
The size of the pole assembly has been reduced, reducing the cost of a tabletop API multi-quad TOF mass spectrometer.
This results in a reduction in size. In one embodiment of the invention, a multiple quadrupole TOF hybrid
The mass spectrometer can be operated so that the selection and fragmentation of ion mass versus charge can be
Performed in a manner that can mimic MS and MS / MS mass spectrometry functions of a quadrupole mass spectrometer
It is. Alternatively, the same multiple quadrupole TOF hybrid mass spectrometer can operate,
Depending on the choice of ion mass vs. charge and ion fragmentation,
MS and MS / MS of three-dimensional ion trap mass spectrometer with multiple steps ⁿ It is performed in a manner that can mimic the mass spectrometry function. Further constituted by the invention
The same multiple quadrupole TOF mass spectrometer is operated by a triple quadrupole three-dimensional ion trap and
MS and MS cannot be performed by other mass spectrometers described in the prior art
/ MSⁿCan work with mass spectrometry function.

In another embodiment of the invention, a multiplex 4 constructed and operative according to the invention
The polar ion guide assembly is included in a hybrid Fourier transform, three-dimensional ion trap or magnetic sector mass spectrometer. In one embodiment of the invention, a segmented multipole ion guide extending continuously into a multiple vacuum pumping step is configured with a Fourier transform, a three-dimensional ion trap or a magnetic sector mass spectrometer trap.

High ion propagation efficiencies are obtained in a segmented multi-vacuum pumping process multipole ion guide, or a multiquadrupole ion guide assembly constructed according to the invention. Ions are
While staying in a constant radial orbit, it traverses between multiple ion guides located in the high pressure vacuum region and configured with a connection point between adjacent axially aligned quadrupole ion guides. As a result, the generation loss of the desired mass-to-charge value is minimal during trapping or traversal in a multi-quadrupole ion guide assembly constructed according to the invention.
In one embodiment of the invention, the amplitude of the individual RF voltage supply that supplies the potential to each individual quadrupole assembly of the installed multiple quadrupole is variable, but the primary RF
And the phase output are the same. As a result, ions having a steady trajectory whose mass-to-charge value (m / z) traverses each quadrupole ion guide assembly can remain in the normal trajectory through all multiple quadrupole ion guide assembly lengths. Ions with low axial translation or kinetic energy move effectively through multi-sectioned or non-sectioned quadrupole ion guides, allowing for high resolution in mass selection or mass analysis tasks.
Ions are also trapped within each multi-sectioned or non-sectioned selected section and to adjacent quadrupoles as required to improve utilization and obtain a wide range of mass spectrometry tasks, or Transferred to TOF mass spectrometer. An important feature of the individual sections of a segmented ion guide operating in multiple ion guide or ion trap mode is
That is, ions continue to enter the opposite end of the ion guide or individual section while the ions are simultaneously released from one end of the ion guide or section. Because of this feature, a segmented ion guide that receives a continuous ion beam only transfers the ion portion located within the ion guide into an axially aligned adjacent ion guide or other mass spectrometer, such as a TOF. Can be selectively released. In this way, no ions are lost during the mass spectrometry step. Ions can also be transferred back and forth between multipole ion guide assemblies or between sections inside the multipole ion guide assembly to perform an array of mass spectrometric tasks not possible with prior art analyzer configurations. Enable.

DETAILED DESCRIPTION OF THE INVENTION A multiple ion guide extending from one vacuum pumping step configured in a mass spectrometer device to at least one additional vacuum pumping step is disclosed in US Pat. 65
2,427. The ion trap inside the multipole ion guide, which is combined with the release of at least some of the ions trapped inside the multipole ion guide following the pulsing of the released ions into the flight tube of the time-of-flight mass spectrometer, It is described in U.S. Patent No. 5,689,111. Operation of MS and MS ⁿ configured APITOF mass spectrometer to obtain the analytical capabilities multipole ion guide is described in U.S. patent application Ser in 08 / 694,542. The invention described in the following sections describes a new embodiment of a multipole ion guide, a new configuration of a multi-pole ion guide assembly, and a new method of operation of the above multipole ion guide and mass spectrometer. Including their incorporation into The invention improves the performance and analytical capabilities of the mass spectrometer configured while reducing the size and cost of the device compared to conventional mass spectrometer configurations in some embodiments.

[0027] Multipolar ion guides have been used for a wide range of functions, including transport of ions in a vacuum, and as ion traps, mass-to-charge filters, and as a means of fragmenting ions. Multipole ion guides include a set of parallel electrodes, poles or rods uniformly spaced at a common radius around a center point. Sine wave voltage or alternating current (AC
Or RF) potential and +/- DC voltage act on the ion guide bar or electrode during operation. Additional AC and DC potentials are set to allow for a steady ion trajectory through a rod length internal volume to a selected range of mass to charge (m / z) values. These same AC and DC voltage potentials are set to produce a non-stationary ion trajectory for ion mass to charge values falling outside the operational stability window. Ions having a non-stationary orbit are emitted radially from the ion guide volume by collision with rods and poles before the ions traverse the ion guide length. Multipole ion guides are typically configured with a uniform set of poles, such as 4, 6, or 8 poles. Odd multipole ion guides are also described, but are not commonly used in commercial equipment. The 4-pole, 6-pole and 8-pole operated solely with the working AC or RF voltage are configured as multipole ion guides in mass spectrometer devices. If ion mass-to-charge selection is required, the resolution of ion mass-to-charge selection can be increased, as well as quadrupole, compared to 6-pole or 8-pole performance. A quadrupole ion guide that operates as a mass spectrometer or mass filter
It is configured with a round bar or even with an ideal hyperbolic bar shape. For the inner rod given the rod spacing (r ₀ ), an effective receiving area for ions to successfully enter the multipole ion guide without being blocked or expelled radially outward from the central volume is an increased pole number Increase with. Multipole ion guides configured with a high number of poles, operating in RF-only mode, transfer a wider range of ion mass-to-charge values in stationary orbit than multipole ion guides configured with a low number of poles It is possible. Due to the performance differences with multipole ion guides having different numbers of poles, the proper choice of ion guide is highly relevant to its application. The term triple quadrupole is conventionally used to describe three multipole ion guide configurations that are axially aligned and located within a common vacuum pumping process. The RF and DC potentials acting on the individual multipole ion guide assemblies within the triple quadrupole are supplied from separate RF and DC feeds.
The "triple quadrupole" collision chamber is configured as a quadrupole, hexapole or octapole ion guide and typically operates in RF only mode.

The multipole ion guide described in the invention is configured with any number of poles. Where individual multipole ion guide assemblies are constructed, a mixture of 4 and 6 or 8 poles is preferred for best performance. A multipolar ion guide rod assembly is disclosed in US Pat. No. 5,843, constructed with segmented, non-parallel or conical rods operating in an RF-only mode.
7, 386 by Thomson et al. Such a bar configuration, operating in RF-only mode with a unipolar DC acting on all bars of the assembly, creates an asymmetric electric field in the Z or axial direction during operation. This axial electric field helps to push the ions through the length of the ion guide more quickly than would be possible with a parallel set of non-sectioning rods for a given application. The presence of the axial electric field, together with the higher background pressure within the multipole ion guide volume, is useful for moving ions through the multipole ion guide. While the addition of an axial electric field promotes the movement of ions through the multipole ion guide, the rod configuration configured to provide an axial electric field impairs mass-to-charge selection resolution and increases manufacturing complexity and cost I do. Conical or asymmetric rod assemblies are used in some embodiments of the invention that use RF-only operation for a given multipole ion guide assembly. In an effort to limit the number of embodiments provided, the invention is described for a multipole ion guide configured with a parallel rod or electrode ion guide assembly. A given axial electric field inside the multipole ion guide assembly acts using a pole section of the RF-only gateway, as described in some embodiments.

The single sectioned multipole ion guide assembly is configured such that at least one section extends from one vacuum pumping step to at least one adjacent vacuum pumping step. In one aspect of the invention, individual multipole ion guides having the same cross-sectional shape are at least between a multipole ion guide assembly located in a high pressure vacuum pumping region where multiple ions are generated for neutral gas collisions. It is configured as an axial alignment assembly with one connection point. The operation of multiple multipole ion guides in the high background vacuum pressure region is effective to obtain analytical functions such as collision induced separation of ions (CID) in the same vacuum pumping step where ion mass versus charge selection is also performed. Used for A segmented or non-segmented multipole ion guide that extends from one vacuum pumping step to another in an atmospheric pressure ion source mass spectrometer device can effectively transport ions over a wide range of background pressures. is there. Multipole ion guides can supply ions from an atmospheric pressure ion source to a mass spectrometer including, but not limited to, a TOF, FTMS, quadrupole, triple quadrupole, magnetic sector or three-dimensional ion trap. Alternatively, a segmented or non-segmented multipole ion guide assembly configured with at least a portion of a multiple ion guide assembly located within the high vacuum pressure region comprises:
It can operate directly as a mass spectrometer with MS and MS / MS analysis capabilities.

An important feature of multipole ion guides operating in ion trap mode is that ions are simultaneously released from one end of the ion guide assembly or section while ions are placed at the opposite end of the ion guide assembly or individual section. It is to enter. This feature allows the multipole ion guide to operate in trap mode while receiving a continuous ion beam, to another ion guide, ion guide section or another mass spectrometer to perform mass analysis on released ions. All or some of the ions located in the ion guide can be selectively released. In this way, ions entering the multipole ion guide from a continuous ion beam are not lost during discontinuous or batch mass spectrometry steps. One preferred embodiment of the invention comprises an API source, three quadrupole ion guide assemblies with at least two quadrupole mass spectrometers operating in mass-to-charge selection and ion fragmentation modes, a time-of-flight mass FIG. 4 is a configuration of a hybrid API source 4-pole TOF mass spectrometer including an analyzer. The multiple quadrupole ion guide assembly constructed in accordance with the invention in such a hybrid API source quadrupole TOF mass spectrometer provides high sensitivity, high mass to charge resolution and high mass measurement accuracy with MS and MS / MS ⁿ analysis capabilities. Enables widespread implementation. In the following description of the invention, three major components are shown, with alternative embodiments described for each component. The first embodiment is a configuration of a multiple quadrupole ion-guided time-of-flight hybrid mass spectrometer device. Hybrid devices as described above include TOF mass spectrometers, but FTMS, magnetic sectors, three-dimensional ion traps or quadrupole mass spectrometers can be substituted for time-of-flight mass spectrometers. The second embodiment uses an individual with at least one connection point between the ion guides in the high pressure vacuum region to obtain MS and MS / MS analysis functions similar to a conventional low vacuum pressure triple quadrupole mass spectrometer. 4 shows a configuration of a quadrupole ion guide assembly. The third embodiment described is located within a higher vacuum background pressure,
And a quadrupole ion guide configuration operating in mass-to-charge selection mode. The third embodiment operates to perform an APIMS mass spectrometry function similar to a conventional single quadrupole mass spectrometer operating at low vacuum pressure. Smaller size high pressure constructed by the invention
Quadrupole ion guidance can improve performance and analytical capabilities while reducing instrument cost and size.

A preferred embodiment of the invention is shown in FIG. Three independent quadrupole ion guide linear assemblies 8 are configured in a four vacuum pumping step hybrid API source multiple quadrupole TOF mass spectrometer. Referring to FIGS. 1 and 2, a multiple quadrupole ion guide assembly 8 comprises three independent quadrupole ion guide assemblies 60, 61 and 6 extending along a common axis 5.
2 inclusive. Alternatively, quadrupole ion guide assemblies 60, 61 and 62 can be composed of six, eight or more rods or poles, but obtain ion mass versus charge obtained using multipole ion guidance. The selection resolution decreases as the number of poles increases. The higher ion mass to charge selection resolution is 4 poles (6 poles), 8 poles (8 poles) or 4 poles (compared to an ion guide with more than 8 poles or an odd number of poles). 4 poles). As a result, quadrupoles are commonly used as mass spectrometers or mass filters. 6 and 8 poles with a wider range of m / z stability windows and a larger effective entrance receiving area, are RF dedicated with and without ion trapping in high and low pressure vacuum regions when compared to 4 poles Used as a collision chamber or ion transfer multipole ion guide operating in mode. The multipole ion guide shown in a given preferred embodiment is described as a quadrupole. However, for some embodiments constructed and operative in accordance with the invention, multipole ion guides configured with more than four poles are more efficient than quadrupole ion guides configured in the described embodiment. It can be easily replaced.

The quadrupole ion guide assembly 60 includes four parallel electrodes and equally spaced poles or rods about the common centerline 5. Each pole contains two sections. Each electrode of section 1 has a tapered entrance contoured to match the angle of skimmer 26. The power supply module 63 applies RF, AC and DC potentials to the poles of both sections of the segmented 4-pole 60. The quadrupole assemblies 60, 61 and 62 are connected to the connection point 7 between each independent quadrupole assembly.
And 10 are configured along a common axis 5 located within the high pressure vacuum process 72. Vacuum process 7
1,72,73 and 74 are typically maintained at pressures of 0.5-3 Torr, 0.1-10 mTorr, 1-8 × 10 ^-5 Torr and 1-5 × 10 ^-7 Torr, respectively. You. Ions experience several collisions with neutral background gas molecules as they traverse the volume defined by the quadrupoles 60, 61 and 62 in the vacuum process 72. In the embodiment shown in FIG. 1, the electrostatic lens is a separate 4-pole assembly 60,61.
Are not configured at connection points 7 and 10 between To avoid fringing field effects and to maximize ion propagation between the quadrupole assemblies, quadrupole ion guide assemblies 60, 61 and 62 have the same radius with each adjacent pole aligned axially. It has a cross-sectional shape. In addition, independent RF generators configured within the power supply modules 63, 64 and 65 can be used to control the same RF frequency and phase in adjacent axially aligned
Configured and tuned to add to a 4-pole electrode. The phase shift between adjacent quadrupoles should be no more than 0.05 cycles to avoid fringing field effects. FIG.
In the embodiment shown in FIG. 6, the primary RF frequency is determined by the resonance frequency operating point for the quadrupole 60 and the RF power supply in the power supply module 63. The primary RF frequency is fed back into the controller 80 and the four pole assemblies 61 and 6 respectively.
It is distributed as a reference oscillator frequency to supply modules 64 and 65 which apply a potential to 2. Adjustable RF phase shifters 89 and 90 respectively adjust the phase of the RF output from power supply modules 64 and 65 such that the axially aligned ion guide poles have the same RF frequency and operating phase. . To reduce the RF power required to drive the quadrupole assemblies 60, 61, the variable capacitive loads 92 and 93 apply the desired RF frequency to the quadrupole assemblies 61 and 62, respectively, for resonant induction and capacitive loading. Adjusted to accommodate. The same polarity DC is supplied by the power supply modules 63, 64 and 65 to the axially aligned rods to minimize fringing field effects.
The power supply modules 63 and 65 supply a resonant waveform or a circular frequency AC (shown as SF in FIG. 2) to the quadrupole assemblies 60 and 62, respectively. The power supply modules 63, 64 and 65 also supply a common offset DC to the poles of the four poles 60, 61 and 62, respectively. The +/- DC, SF and offset DC potentials can be quickly added to the quadrupole by switching circuits from the multiplex feed, or the voltage can be changed by digital to analog (DAC) input control. The offset DC provided by the power supply module 60 needs to change quickly for any analysis function. This is achieved by switching between the +/- DC power supplies of the multiple presets to avoid fusing time for DAC input changes to the DC power supplies. When working with working +/- DC, the DC offset potential is obtained by adding symmetric + and-DC amplitudes. The multiple DC power supply outputs are passed through lenses 83, 26, 33, 34, 41 through +/- DC power supply modules 66 and 67, respectively, to obtain the analysis function described below.
And 42 quickly.

The individual quadrupole ion guide assembly 60 and 62 are independently operated in mass-to-charge selection and ion crushing mode, obtain MS / MS ⁿ function with a time-of-flight mass spectrometry. The segmented ion guide 60 uses the same RF voltage supply 63 to segment the RF voltage
And 2 through connections 68 and 69, respectively. The junction 6 between sections 1 and 2 is configured to allow some capacitive coupling between adjacent axially aligned poles. The RF potential to section 1 is supplied through this capacitive coupling,
Alternatively, the power is supplied directly from the power supply module 63. The different DC offset potentials acting on sections 1 and 2 of the segmented ion guide 60
Direct ion motion through zero or trap ions within section 1 or 2 or both. Section 1 of quadrupole assembly 60 typically operates in RF-only mode, and when section 2 of quadrupole 60 operates in mass-to-charge selection or ion fragmentation mode, the fringing field for section 2 containing ions. Minimize the effect. Connection points 7 and 10 between quadrupole assemblies 60 and 61 and 61 and 62, respectively, are constructed in accordance with the invention to minimize resonant frequency waveforms acting on capacitively coupled or independently operated quadrupole assemblies 60 and 61. Become Constructive or destructive interference with the working resonance waveform is avoided by minimizing capacitive coupling between the quadrupole assemblies 60 and 62 during ion mass versus charge selection and fragmentation operations. With independent RF and DC power supply 64
The quadrupole assembly 61 prevents or minimizes capacitive coupling between the quadrupole assemblies 60 and 62, while minimizing ion transfer efficiency along the multiple quadrupole assembly axis 5. Alternatively, as shown in FIG. 5, a four-pole assembly 61 comprises a single flat electrode including an opening centered on centerline 5 with DC acting to electrically insulate four-pole assemblies 60 and 62. Is configured as The preferred embodiment as shown in FIG. 1 includes an arrangement of a quadrupole assembly 61 having the same radial cross-section as quadrupole assemblies 60 and 62 with the poles aligned in the axial direction.

In an ideal quadrupole ion guide, the shape of the poles is hyperbolic, but generally round bars are used for ease of manufacture. Round bars 104, 105, 106 and 107
The cross section of the four poles is shown in FIG. The same RF, SF and DC potentials work for most quadrupole operating modes to opposite pole sets (104, 106 and 105, 107). Adjacent poles have the same primary RF frequency and amplitude, but 18
It has a different phase difference of 0 °. When the offset or common DC potential is subtracted, generally the amplitude of adjacent poles is the same, but the working polar DC potential is the opposite. In addition to the primary RF potential, a multiple resonance frequency AC waveform voltage is applied to the quadrupole to obtain ion mass versus charge selection and ion fragmentation functions. A common DC offset also affects all rods 104, 105, 106 and 107. Primary RF, opposite +/- DC, common DC and resonant frequency AC potentials are added simultaneously or individually to the poles of the quadrupole ion guide to obtain a range of analytical functions. In a segmented ion guide assembly, each bar or pole section is electrically insulated to affect different amplitudes RF, SF and each section of the segmented ion guide assembly.
Enable DC. In FIG. 1, nodes 6, 7, and 10 are configured to provide electrical isolation, while minimizing any space charge offset that distort the electric field within the area bounded by the bars. Junction points 6, 7 and 10 between quadrupole assemblies 60 and 61 and 61 and 62, respectively, are also configured to minimize RF field distortion so that individual quadrupole ion guides 60 within multiple ion guide assembly 8 are also provided. , 61 and 62 are maximized.

In the embodiment shown in FIG. 1, the inlet ends of the segmented quadrupole assembly 60, quadrupole assembly 61 and multi-vacuum process quadrupole assembly 62 have an operating background pressure of 1 × 10 ⁻⁴ torr. Located within a large second vacuum pumping step 72. Typically, ions traversing the length of the multiple quadrupole assembly at background pressures greater than 1 × 10 ⁻⁴ Torr maintained within the 1-10 mTorr range will encounter collisions with a neutral background gas. One or more quadrupole assemblies of the multiple quadrupole ion guide assembly 8 operate in a mass-to-charge selection mode. The selection of mass to charge is obtained by adding a combination of RF and DC potentials, adding individual resonance frequencies with sufficient amplitude to prevent unwanted ion m / z values. Those parts of the multiple quadrupole guide assembly 8 located in the high pressure region of the vacuum step 72 may also be in the ion transfer, ion trap and collision induced separation and fracture modes and in the m / z selection mode or in these individual modes of operation. Configured to work in some combination. Activating a multipolar ion guide at high background pressure in an APIMS system is disclosed in US Pat.
As described in FIG. 6, the ion propagation efficiency is improved. In a mass-to-charge filter or mass-to-charge selection mode of operation, as the ions traverse the multipole ion guide length in a single pass or multiple pass ion trap mode, the ions slowly move to the selected ion m / z trajectory. Below and radially and axially with the background gas. Ions that spend an increased amount of time in a multipole ion guide are subjected to an increased number of RF cycles. In this way, higher m / z select resolution than can be obtained using a quadrupole mass spectrometer with a number of conventional operating methods in a single pass, no trap mode without slow background pressure collisions, Obtained for shorter multipole ion guide lengths. Activating the multipole ion guide in the mass selection mode in a high pressure background gas allows for the construction of a smaller mass spectrometer device with reduced vacuum pumping speed requirements. A compact multipole ion guide arrangement reduces the cost of the RF power supply, and higher pressure operation reduces the cost of the vacuum system. Equipment configured with segmented multipole ion guides can perform ion mass-to-charge selection and ion fragmentation at higher background pressures while delivering generated ion populations into low vacuum pressure regions with high ion propagation efficiency To

The electric spray probe 15 shown in FIG.
It is configured to accommodate the solution flow rate to the probe tip 16 over min or more.
Alternatively, the APIMS embodiment shown in FIG. 1 includes an atmospheric pressure chemical ionization (APCI) source, an inductively coupled plasma (ICP) source, a glow discharge (GD) source, an atmospheric pressure (MALDI)
) Configured with a source or other atmospheric pressure ion source type. The API source is configured with multiple probes or combinations of different probes within one source, as described in US patent application Ser. No. 08 / (). Chemical ionization (CI), electron ionization (EI), fast atom bombardment (FAB), fluidized FAB, laser desorption (LD)
Ion sources operating in vacuum or partial vacuum, including, but not limited to, matrix-associated laser desorption ionization (MALDI), thermal spray (TS) and particle beam (PB), are also suitable for the hybrid mass spectrometer device shown in FIG. It is composed with. The sample holding liquid is introduced into the ES probe 15 using various liquid supply devices. Liquid supply devices include, but are not limited to, liquid pumps with or without automatic injectors, separation devices such as liquid chromatography or capillary electrophoresis, syringe pumps, pressure vessels, gravity supply vessels or solution tanks. Not restricted. ES source 12 operates by applying an electrical potential to cylindrical electrode 17, end plate electrode 18, and capillary entrance electrode 19. Counter-current drying gas 21 is directed through heater 20, through hole 22 in end plate lug 24, and into the ES source chamber.
The hole or channel 57 through the dielectric capillary 23 includes an inlet hole 13 and an outlet hole 14. The potential of the ions migrating into the vacuum through the dielectric capillary 23 changes the potential there relative to ground, as described in US Pat. No. 4,542,293. The ions enter and exit the dielectric capillary at a potential energy approximately equivalent to the entry and exit electrode potential, respectively. The use of dielectric capillaries 23 allows different potentials to be applied to the inlet and outlet ends of the capillaries during operation. This effectively separates the API source both physically and electrostatically from the vacuum area, allowing for independent optimization adjustment of both areas.
To create positive ions, a negative kilovolt potential acts on the end plate electrode 18 and the capillary entry electrode 19 along with the cylindrical electrode 17 and the attached electrode projections 24. ES probe 15 remains at ground potential during operation. Electrode 1 to create negative ions
7, 18 and 19 are reversed with ES probe 15 remaining at ground potential. Alternatively, if a nozzle or conductive (metal) capillary is used as a hole into the vacuum, a kilovolt potential may be applied during operation, along with a low potential acting on the cylindrical electrode 17, end plate electrode 18 and electrode 19, as well as the ES probe 15. Act on The API source potential is no longer decoupled from the vacuum region potential because the entrance and exit potentials are equal due to the conductive holes or capillaries. The heated capillary is configured as a hole into a vacuum used with or without countercurrent drying gas. Capillary outlet heater 25
Is configured with a dielectric capillary tube 23 and independently heats the outlet of the capillary tube 23.

Electrosprayed droplets, along with the appropriate potentials acting on elements into the ES source 12, are made from the solution supplied to the ES probe tip 16. Electrospray charged droplets from the solution exiting the ES probe tip 16 are repelled against the backflow dry gas 21 by the electric field created by the relative potentials acting on the ES probe 15 and the ES chamber electrodes 17, 18 and 19. The atomizing gas 48 is added through a second laminar tube surrounding the first laminar tube for sample introduction to assist the electrospray process in forming the charged droplets. As the droplets evaporate, ions are formed and these ionic portions migrate through the capillary holes 57 into the vacuum. Vacuum bulkhead 53
Includes a vacuum seal with the dielectric capillary 23. If the heated capillary is configured with or without countercurrent dry gas as a hole into the vacuum with heater 25, evaporation of the charged droplets and generation of ions will occur when the charged droplets pass through the first vacuum pumping step 7.
As it traverses the length of the capillary 23 towards 1, it occurs in the capillary hole 57. The neutral background gas forms a supersonic jet as it expands into the vacuum from the capillary outlet hole 14 and during expansion causes ions to migrate through multiple collisions. The ion portion entering the first vacuum step 71 is directed through the holes 27 and into the second vacuum step 72.

The hybrid quadrupole TOF mass spectrometer shown in FIG. 1 is configured with four vacuum pumping steps, during operation, as the ions of interest traverse from the API source through each vacuum step, the background neutral gas Remove. The cost and size of the API / MS device is reduced when it is configured with multiple vacuum pumping steps, and the pumping speed required for each step is minimized. Typically, three to four, and possibly four or more vacuum pumping steps are used in the API / MS equipment. With the development of intermediate stage turbomolecular vacuum pumps, three-stage (and even four-stage) vacuum systems require one rotary and one or two turbomolecular pumps to obtain sufficient background pressure in each stage. Just do it. A multipole ion guide operating in AC or RF only mode is configured in the API / MS device to carry ions through the second and / or third vacuum pumping steps 72 and 73, respectively. In the four vacuum pumping step embodiment shown in FIG. 1, a rotary vacuum pump is used to evacuate the first vacuum step 71 through the pumping port 28 and the background pressure is maintained within the first vacuum step 71, typically , 0.2 and 3 Torr.
The skimmer 26 forms part of the vacuum septum 52 and divides the first and second vacuum pumping steps 71 and 72. The background pressure in the second vacuum step 72 is typically 10 ⁻⁴ to 2 × 10 ⁴ depending on the size of the skimmer holes 27 used in the second vacuum step 72 and the pumping speed through the vacuum pumping port 29. Within ^-1 torr
.

The ions entering the second vacuum step 72 through the skimmer hole 27 enter the segmented quadrupole ion guide assembly 60 where they are radially trapped by the electric field acting on the quadrupole. The locally high pressure in the entry region 9 of section 1 of the sectioned quadrupole assembly 60 attenuates the ion trajectory as they pass through the quadrupole RF fringing field. This collision, which attenuates the ion trajectory in the locally high pressure region 9, results in a high trapping efficiency for ions entering the quadrupole assembly 60. The ion m / z value that falls inside the operational stability window remains radially confined within the interior volume described by the bar of the quadrupole assembly 60. The trajectory of ions coming within the stability window defined by the potential acting on the poles of the quadrupole section 1 decay toward the centerline 5 while traversing the length of section 1. The ion trajectory that is attenuated to a trajectory in section 1 effectively moves to section 2 of quadrupole assembly 60 when an appropriate relative bias voltage is applied between sections 1 and 2. For many applications, Section 1 of quadrupole assembly 60 operates in an RF-only mode. Similarly, when a suitable relative bias or offset potential acts between the poles of section 2 of quadrupole assembly 60 and poles 3 and 4 of quadrupoles 61 and 62, respectively, section 2 poles of quadrupole 60 Can pass through quadrupole 61 into quadrupole assembly 62. The ions pass into the third vacuum pumping step while the quadrupole assembly 6
Cross two lengths. Each bar 4 of the four-pole assembly 62 passes through the vacuum bulkhead 32, but is electrically isolated therefrom. The third vacuum step 73 is evacuated through the vacuum pumping port 30. The ions exit the multiple quadrupole assembly 8 at the exit end 11 and pass through electrostatic lenses 33, 34 and 35 into the quadrature pulsed region 37 of the time-of-flight mass spectrometer 40. The lens 33 has a third and fourth vacuum pumping steps 73 and 74.
Between them as a part of the vacuum partition 36.

The time of flight mass spectrometer 40 comprises a fourth vacuum step 74, which is evacuated through the pumping port 31. The fourth vacuum step 74 is typically maintained in a vacuum pressure region of low 10 ^-6 to low 10 ^-7 Torr. T
The OF pulsed region 37 is bounded by electrostatic lenses 41 and 42. Multiplex 4
Ions exiting the pole assembly 8 move into the TOF pulsing region 37. Ions traversing the pulsed region 37 are pulsed into the TOF floating region 58 or continue to pass through the hole 55 in the lens 54 through the pulsed region 37. Lens 54,
By applying appropriate voltages to the electron multiplication detector 38, the conversion dynode 39 and the Faraday cup 56, ions passing through the hole 55
Head or collide on the Faraday cup 56. After ion bombardment, secondary electrons or photons released from conversion dynode 39 are detected by electron multiplication detector 38. In the embodiment of the hybrid mass spectrometer shown in FIG.
The ions entering the OF pulsing region 37 are subjected to TOF mass spectrometry, and the
8 or at the Faraday cup 56. The ions enter the TOF pulsing region 37 when the lenses 41, 42 and 43 are set to approximately the same potential. In the TOF configuration shown in FIG. 1, the TOF floating region 58
When a suitable voltage is applied to lens 60, it is maintained at a kilovolt potential. TOF
In operation, a negative voltage is applied to the lens 60 for positive ions and a positive voltage acts on the lens 60 for negative ions. TOF maintained at kilovolt potential
Due to the floating region 58, the voltage value around ground acts on the pulsed lenses 41, 42 and 43 as the pulse enters the pulsed region 37. Positive ions raise the potential of pulsed lens 41 to a constant positive voltage, raise 42 to approximately half that positive voltage,
And by applying a ground potential to the lens 43, it is accelerated or pulsed into the TOF floating region 58. Positive ions are accelerated out of the pulsed region 37 and into the entrance region 49 of the TOF floating region 58. The velocity of the ions traversing the floating region 58 remains constant until the ions enter the ion reflector 50 at the entry point 51.
Ions entering the ion reflector 50 are first decelerated and then reaccelerated, starting at point 45 and exiting the reflector 50 at point 45. Ions traversing the TOF floating region in the opposite direction
From point 46, they are accelerated onto the surface of a detector 47 which detects them. Negative ions are pulsed from pulsed region 37 and directed to the surface of detector 47 by reversing the voltage polarity in a similar manner. Ions are typically pulsed from pulsed region 37 at a pulse rate of up to 20,000 times / second, limited by the time of flight of the highest m / z value of the ion being detected. The individual mass spectra generated per TOF pulse are summed to create a total mass spectrum stored on disk in the computer. A TOF mass spectrometer capable of storing a total spectrum of 100 times / second or more on a disk has been developed. The signal generated by the detector 47 is an analog / digital (A / D) converter or a time / digital converter (T
DC) in the data acquisition system. Time-of-flight mass spectrometer 40 has the ability to detect a full mass spectrum of all m / z values of ions traversing pulsed region 37. The TOF mass spectrometry process starting with orthogonal pulses of ions into the floating region 58 is multiplexed prior to the generated ion population entering the pulsed region 37
Separated from any trapping, non-trapping, mass selection or ion fragmentation steps occurring within the quadrupole assembly 8. The TOF mass spectrometer 40 provides a sufficient mass spectrum with maximum resolution and sensitivity, with a rapid spectrum acquisition rate independent of the ion mass versus charge selection or ion fragmentation process performed in the multi-quadrupole assembly 8. Can be obtained.

Focusing the population of ions supplied to the pulsed region 37 with the minimum energy axial component changes the scope of the analytical function to change the best adjustment of the TOF mass spectrometer 40 upstream of the pulsed region 37. Obtained without. The embodiment of the hybrid mass spectrometer shown in FIG. 1 employs a number of different ion mass versus charge selection and ion fragmentation techniques to accommodate various M
Composed of S and MS / MS ⁿ experiments as practicable. Some combinations of m / z selection, ion fragmentation, and mass spectrometry can be performed sequentially or simultaneously using the embodiment shown in FIG. At least five of the following individual techniques are used to perform collision-induced split ion fragmentation.

1. DC ion acceleration by high pressure gas in the capillary to the skimmer area. 2． Single or multiple ion resonance frequency excitation spallation in a quadrupole ion guide 60 or 62 with or without an ion trap. 3． From one quadrupole to another, with or without an ion trap, or from one quadrupole section to another, DC ion acceleration in the axial direction within the multiple quadrupole assembly 8. Four. 4. High energy reverse DC ion acceleration into the multiple quadrupole assembly 8 by switching the potentials acting on the exit lenses 33 and 34, or Overfilling of the quadrupole guide 60 or 62 in the ion trap until CID fracture occurs.

Each of these ion CID crushing techniques, individually or in combination,
Used in multiple quadrupole assembly 8.

At least four, individual single or multiple, ion mass versus charge value selection techniques are used with multiple quadrupole assemblies 8, including the following four:

1. Blocking resonance frequencies of undesired mass-to-charge values with or without traps within a given quadrupole or segmented quadrupole section. 2. Applying AC and +/- DC potentials to the poles of a quadrupole or compartmentalized quadrupole assembly compartment to obtain ion mass versus charge selection with or without traps. 3. Scans RF amplitude or frequency, with or without trap
Removing unwanted, ion mass versus charge values from a pole assembly or section of a segmented quadrupole assembly. 4. Controlling the release of trapped ions into the TOF pulsed region 37 as described in US Pat. No. 5,689,111.

The mass-to-charge selection statements shown above are each used individually or in combination within the hybrid quadrupole TOF shown in FIG. The combination of m / z selection and disruption techniques can operate for best performance for a given analytical application. Some examples of combination techniques in order to obtain the best MS or MS / MS ⁿ given below.

[0047] Mass versus charge selection or ion fragmentation is performed in quadrupole ion guidance with an ion trap. Mass-to-charge selection along with an ion trap means that ions in the primary ion beam undergo ion mass-to-charge selection or ion CID fragmentation.
This is done with or without preventing entry into the four poles. Electric spray source 12
Supplies a continuous ion beam into the vacuum. Due to the trapping and release of ions within the multiple quadrupole assembly 8, a continuous ion beam from the ES source 12 can be used in US Pat.
9, 111, is effectively converted into a pulsed ion beam with very high utilization into the TOF pulsed region 37. The multiple 4-pole assembly 8
Individual quadrupole or segmented quadrupole sections are operable in a non-trap or trap mode that selectively operates in a trap or non-trap mode. A special example of a segmented ion guidance mode of operation, with and without an ion trap, MS, M
It described below as a means of obtaining S / MS and MS / MS ⁿ analysis function. In the simplest case, multiple quadrupole assembly 8 applies the same AC and DC potentials to quadrupole assemblies 60, 61 and 6
By adding it to all sections 2 it can effectively operate as a sectioned ion guide. Single quadrupole MS and MS / MS ⁿ TOF actuation sequences are described in US patent application Ser.
94,542, and is hereby incorporated by reference. An analysis sequence using multiple quadrupoles operating in ion mass versus charge selection and ion fragmentation mode is described below.

MS experiments with and without ion fragmentation are performed with a number of analytical variants. When a particular range of ion mass to charge is concerned, the multi-quadrupole ion guide assembly 8
One or more of the quadrupole ion guides can operate in m / z select mode. 4-pole assembly 6
Actuation of mass-to-charge selection using 0 or 62 is performed in an ion trap or single pass non-trap mode. M / z of ions entering TOF pulsed region 37
Reducing the charge range improves utilization and performance of the TOF device. Pulsedly reducing the range of mass-to-charge value ions into the TOF floating region 58 increases the TOF pulse rate and utilization in non-trapping ion guidance operations. When a wide range of ion m / z values are pulsed into the TOF floating region 58, the pulse rate is limited by the time of flight of the heaviest ion m / z. When all ions from the preceding pulse strike the detector 17 since the next TOF pulse occurs, the ions from the preceding pulse arrive during the acquisition of the subsequent pulse and have a signal within the acquired mass spectrum. Bring nozzle. Restricting the range of ions m / z entering the TOF floating region 58 allows setting of the maximum TOF velocity, while removing the chemical noise contribution from adjacent pulses. Preventing unwanted ion m / z values from entering the TOF floating region 58 allows for a more effective detector response to those ion m / z values of interest. When ions bombard a channel of a multi-channel plate (MCP), that channel requires a certain recovery time to recover the charge reduction.
The charge decay recovery time is on the order of 1 millisecond, during which no ions impacting on this channel are detected or the secondary electron yield is reduced. For example, low m
The arrival of ions from a strong solvent peak signal with a / z value is independent of any particular analytical experiment, but a significant number of detections in each TOF pulse preceding the arrival of a high m / z value in the same pulse Weaken the instrument channel. Impact of the solvent peak m / z ions on the detector will cause incomplete signals from subsequently arriving ions. From the multipole ion guide prior to TOF pulsing to limit the ion population pulsed into the flight tube suspension region 56 only to those m / z values relevant to the analysis for a given application, Radiating the unwanted m / z ions radially helps to improve TOF sensitivity, consistency in detector response, and increases detector life.

Non-trap or trap mass-to-charge selection is performed in quadrupole assemblies 60 and 62. The m / z of the ions entering the TOF pulsing region 37 is 300 to 500 m /
Consider an example where it is desirable to limit to a range up to z. This can be obtained in a number of ways as described in the examples below. 1. The segmented quadrupole assembly 60 operates with a low mass cutoff of 300 m / z by adding the appropriate RF and +/- DC to the poles of segment 2. 4-pole assembly 61 operates in non-trap RF only mode and 4-pole assembly 62 is 500 m
Operates in trap mode with a high mass cutoff of / z. 4-pole assembly 62
The high mass-to-charge cut-off operation within is obtained by adding to the quadrupole 4 with multipole resonant frequency ion emission, while adding the appropriate RF and +/- DC amplitude to m / The m / z stability window for the z value is 500 m /
z or less. The ions are trapped in the quadrupole assembly 62 and released into the TOF pulsing region 37 by gating the ions out of the exit end 11. The potential acting on the lens 33 is switched to a potential at which ions in the quadrupole assembly 62 are trapped, and to a lower potential at which ions are released. Alternatively, the combination of both high and low potential switching on both lenses 33 and 34 or by switching the offset voltage value of quadrupole assembly 62 traps and releases ions from quadrupole assembly 62, respectively. Used for Such an ion trap and release technique is described in U.S. Patent No. 5,689,111. The ions trapped in quadrupole assembly 62 are applied by applying an appropriate relative offset potential to pole 3 of quadrupole assembly 61 and the pole of section 2 of quadrupole assembly 60.
Returning into pole assembly 60 is prevented. In this manner, ions passing through the multipole quadrupole ion guide assembly 60 having a mass-to-charge value of 500 or more and 300 or less,
Blocking before entering the TOF pulsing region 37. 2. Section 1 of the segmented quadrupole assembly 60 operates in a non-trap RF only mode to maximize ion propagation into Section 2. The RF and +/- DC amplitude values act on the poles of Category 2 to pass ions in the mass to charge value range between 300 and 500.
The quadrupole ion guide assembly 62 operates in an RF-only trap and release mode, where the timing of ion gate release and TOF pulse delay is 10,000 Hz.
The pulse m / z value in the range of 300 to 500 is set into the TOF floating region 58 which operates at a speed of. 4 pole assembly 60 rods of categories 1 and 2, 4-pole assembly 61
The individual DC offset potentials acting on rods 3 and 4 of quadrupole assembly 62 are:
It is set to allow the propagation of ions from the entrance region 9 of the multi-pole assembly 8 to the quadrupole assembly 62. The DC offset potential difference across each section and quadrupole junction is a DC offset as ions are accelerated from one section or quadrupole into a subsequent section or quadrupole assembly.
It is set low enough to avoid accelerated CID crushing. 3. Section 1 of the segmented quadrupole assembly 60 operates in a non-trap RF only mode to maximize ion propagation into Section 2. The resonance excitation frequency range is added to the RF potential acting on the Category 2 bars to block ions above m / z 500 and below m / z 300. Section 4 operates in a dedicated trap and release mode pulsed at a rate of 10,000 Hz. The DC offset potential across each section or quadrupole junction is set to move the ions forward through the multiple quadrupole assembly 8 without causing DC accelerated CID fragmentation of the ions.

Other combinations of the operation of the multiple quadrupole 8 are implemented to obtain a selected mass-to-charge value provided into the TOF floating region 58. Based on the purpose of the analysis, the choice of m / z selection or spallation in each multiple ion guiding section should be made to maximize performance, especially with respect to propagation efficiency. RF and + // to obtain mass selection within 4 poles
The addition of -DC reduces the effective inlet ion receiving aperture and greatly reduces the efficiency of ion propagation to the relevant ion mass versus charge value. When mass-to-charge selection is obtained with resonant frequency excitation emission of unwanted ions, the quadrupole operates essentially RF only so that the effective inlet ion receiving area or aperture is not reduced. The mass-to-charge selection along with the resonance frequency excitation emission of the undesired ions is also a split multiple ion m / z that emits an ion m / z value that falls between the selected ion m / z values.
Allow selection of values. If the narrow ion m / z value is, for example, 20 given above
If one mass to charge unit width is desired for MS / MS experiments, rather than in the 0 m / z range, the m / z selection technique that gives the highest propagation efficiency is selected. To select a higher resolution m / z, a combination of RF and DC m / z selection techniques with resonant frequency excitation radiation, or traps, either uniformly or in combination, can be applied to individual quadrupole assemblies 60, 61 and 62 or Affects single or multiple sections of quadrupole assembly 60. The ion trap during ion mass versus charge selection gives the ion population within a given section or quadrupole a greater number of RF cycles to release to adjacent sections,
Effectively increases the resolution of mass versus charge selection. Ion bombardment with background neutral gas pressure in the second vacuum step helps to maintain a stable ion trajectory in multiple quadrupoles 8 for those ions that fall within the ion guide stability window. The ion trap in a given section or quadrupole assembly is determined by the voltage acting on the poles or each section or quadrupole assembly to be emitted from the quadrupole volume to a neutral gas impingement in the presence of ions, Gives time to ions that fall outside the stability window. The exit end of quadrupole assembly 62 is in a low pressure region where ions to neutral collisions are minimized or eliminated. Due to the lack of a collision damping effect in this low pressure portion of the quadrupole assembly 62, ions m / z values that fall outside the stability region are more quickly emitted from the ion guide volume.

While different RF frequencies act on each section of the multiple quadrupole ion guide 8 or rods of the quadrupole assembly, adding the same RF frequency and phase to quadrupole assemblies 60, 61 and 62 requires Or minimize the fringing field effects experienced by ion traversal between quadrupole assemblies and maximize the efficiency of ion transfer from one section or quadrupole to the next. However, the section RF amplitude is set to a different value for each section or quadrupole assembly to perform different analysis functions from one quadrupole assembly to the next. Each 4-pole assembly 6
At least a portion of 0, 61, and 62 are located within the region of high background vacuum pressure so that each quadrupole assembly, individually or in combination, can perform ion fragmentation from mass to charge and / or CID. . The electronic cost is reduced when the RF potential acting on each quadrupole assembly in the multiple quadrupole assembly 8 is supplied from a single RF power supply. However, a single RF power supply reduces the range of analytical capabilities for the hybrid TOF shown in FIG. The compromise between instrument cost and instrument performance is determined based on the requirements of the particular analytical application. In most analytically capable instruments, the set of poles in each quadrupole assembly 60, 61 and 62 of the multiple quadrupole assembly 8 is individually and independently controlled +/- DC, RF, and sec. Alternatively, it is connected to the resonance frequency supply unit as shown in FIG. Analysis function range is RF frequency, amplitude, offset DC
It is obtained by independently controlling the amplitude, +/- DC amplitude and resonance frequency amplitude and frequency spectrum. The amplitude and frequency components of the resonance waveform supplied from the independent waveform generator in the power supply units 63, 64 and 65 in FIG.
Used to add a simple or complex AC waveform to the poles of 61 and 62. The additional set of secular frequency waveforms serves to obtain a simultaneous or sequential range of mass to charge selection and / or CID fragmentation analysis capabilities. At a minimum, each section of each quadrupole ion guide assembly has an independent DC offset power supply that rapidly switches the DC offset value for a given section of each quadrupole assembly during the analysis sequence. Having.

The conversion dynode 39 along with the detector 55 is configured to detect ions that traverse the pulsed region 37 and are not pulsed into the TOF floating region 58. Section 2 of quadrupole assembly 60 or quadrupole assembly 62 of multiple quadrupole assembly 8 operates in a non-trapped, mass-to-charge selective scan mode with ions detected by detector 38. Alternatively, the ions are spalled with resonant frequency excitation in quadrupole assembly 60 while mass to charge scans quadrupole 62. Multiple quadrupole assembly 8 selects ion mass-to-charge values within quadrupole assembly 60 and DC accelerates the selected mass-to-charge into quadrupole 61, resulting in CID fragmentation and mass-to-charge scanning. 4 poles 6 with enough energy
2 can be operated in the RF-only mode, and the detector 38 can operate in the triple quadrupole mode by detecting the fragment ion peak. The ions leaving the section are TOF
The light is detected on the detector 38 through the pulsed area 37 and the opening 55 of the lens 54. Alternatively, the ions are detected using a Faraday cup 56. The use of TOF to generate a sufficient mass spectrum from the ions exiting quadrupole assembly 62 is compared to the analytical technique of quadrupole 62 of multiple quadrupole ion guide assembly 8 that utilizes mass-to-charge scanning. , Giving higher analytical utilization.

The quadrupole assemblies 60, 61 and 62 configured in the multiple quadrupole assembly 8 are individually
Or, in conjunction, operate in both trapped and non-trap modes with DC accelerated spallation, resonant frequency excited CID, RF and +/- DC with spallation and mass-to-charge selection and resonant frequency emission of unwanted ions. The best 4-pole shape, split,
The gas pressures and components, RF and +/- DC amplitudes and additional secular frequencies and the timing of RF and +/- DC and SF potentials are not the same for each of the analytical functions described above, and the relevant mass-to-charge values. It changes with ions. The individual variables and operating conditions that require optimization are not limited to: 1． Quadrupole Shape Relatively small rods relative to rod spacing (r 0) give shorter distances before being emitted from the quadrupole ion volume in the mass-to-charge selection of the resonance frequency excitation to the ions to be moved. Lower r 0 also allows lower neutral gas conductance due to multiple vacuum step ion guidance. Conversely, bars that are relatively small relative to the bar spacing are 4
The pole trap volume is greatly reduced, increasing the space charge effect in trap mode more quickly. Non-hyperbolic quadrupoles create a non-quadrupole or higher order (6 pole, 8 pole, etc. field component) electric field within the quadrupole ion guide volume when a sinusoidal potential is applied. In order to improve performance, the application of higher multi-pole electric fields is widely practiced in three-dimensional ion trapping structures and operations. Each quadrupole section or assembly length affects the number of RF cycles exposing ions in single pass mode. 2. Neutral Gas Components In DC accelerated CID fragmentation, relatively heavy neutral gases are preferred to improve ion fragmentation efficiency for a given ion acceleration energy. Resonant frequency excited CID ion spallation favors relatively light neutral gases, reducing the center of mass vibrational energy and potential loss from fragment ion scattering. The invention involves the addition of a supplemental gas in a second vacuum step as shown in FIG. 4 to allow for partially changing ion bombardment gas, and introduces a reactant gas if required for analytical applications. 3. Neutral gas pressure Longer mean free paths during collisions or lower pressures are advantageous for unwanted m / z ion emission without premature fragmentation. Shorter mean free paths are preferred for DC accelerated fracturing. 4. Variable Frequency and Amplitude Secular Frequency Waveform The timing sequence that optimizes the frequency and amplitude components of the circular waveform and adds the above waveform to maximize performance for ion mass versus charge isolation and resonant frequency excited CID ion fragmentation is analyzed. Greatly depends on the application. 5. RF and +/- DC Amplitude The amplitude of the RF and +/- DC potential acting on a given 4-pole rod is determined by the ion mass to charge ion isolation or resonance frequency. It changes to move the frequency effectively. 6. Different DC offset between quadrupole assemblies Longer acceleration of ions through the background gas can be a simple,
Less scattering loss occurs when compared to fast acceleration. Multiple division is RF
Allows gradual acceleration of ions in the presence of an electric field.

Alternative embodiments of the invention described herein provide different compromises for optimizing the variables set forth above for different analytical applications.

Higher resolution mass-to-charge selection generally requires MS / M in MS analysis as described above.
Required when it is necessary to perform the ^Sn function. The resolution is determined by comparing the ion mass versus charge value that can be passed in a stable orbit or trapped in the quadrupole ion guide, as compared to their ion mass versus charge value emitted from the quadrupole ion guide. Function. Typically, the four poles 60, 61 and 62 of the multi-assembly 8 operate to pass or trap ions with a stable mass-to-charge value in the first stable region 102 as shown in FIG. "Quadrupole mass spectrometer and its applications"
Solving the equation of ion motion in quadrupole ion guidance, as explained by Dawson in Chapter 2 of Erbia Science Publishing Company, New York (1976), the first stable region shows that the Mash-parameters Au and Qu Is determined by the solution of a _u = a _x =-a _y = 4 zU / mw ² r ₀ ² (1) q _u = q _x =-q _y = ² zV / mw ² r ₀ ² (2) U is +/- DC amplitude and m is Ion mass, z is ion charge, V is RF amplitude, r ₀
Is the distance inside the surface from the center line to the quadrupole, and ω (= 2πf) is the angular frequency of the applied RF electric field. The solution of the equation of motion plotted is the function of Au and Qu shown in FIG.
Is given by the o-β line. Only those ions with mass-to-charge values that fall within the operation stable region 102 as shown in FIG. 12 are stable in the X and Y (radius) directions during ion trap or ion propagation operation modes in quadrupole ion guidance. Has an orbit. In low vacuum pressure quadrupole ion guidance operation, the selection of mass to charge is typically made by operating near the top 100 of the stability region 102, where Au = 0.36699, Qu = 0. 70600. As Dawson shows, ions with mass-to-charge values approaching the stability diagram boundary increase the magnitude of the radial oscillation, resulting in ion loss due to collision with the rod. Stable region 10
Actuation of the quadrupole ion guide near the top 100 of the 2 increases the resolution in +/- DC and RF mass-to-charge selection, but results in the loss of ions of the selected mass-to-charge value. The exact location of the stable boundary to individual ion mass versus charge is modified by physical, electrical and ionic space charge factors. Imperfections in the electric field inside the quadrupole ion guide volume due to non-ideal size or shape or electronically controlled tolerances, ion position in the quadrupole field and space charge in the quadrupole ion guide, can result in a given ion Is the source of inaccuracy at the exact location of the stability region boundary with respect to For example, a round bar generates a higher order electric field inside the quadrupole volume, distorting the boundaries of the stable region 102. In the presently disclosed invention, the mass-to-charge selection, along with mass-to-charge values that, when operating near the stability region boundary, experience an increase in the scalar frequency amplitude oscillation,
It is performed in the presence of a background gas that results in CID fragmentation of the ions. Unwanted CID spallation also occurs with resonant frequency ion emission, as is known in mass-to-charge selection or isolation in three-dimensional ion traps. Several actuation techniques have been developed in three-dimensional ion trap RF-only operation with minimal loss of selected ions to obtain a high resolution mass-to-charge selection. The resonance or circular frequency S0 of the radial ion motion traversing or trapped in the quadrupole ion guide is expressed by the following approximation for β <0. s ₀ = q _u w ₀ / (8) (3) The exact circular frequency for a given mass-to-charge value is provided by the same physical, electrical and ionic space charge elements that result in a stable boundary.

During the quadrupole ion mass-to-charge selection operation in the presence of the background gas, the radial trapping energy is maintained sufficiently deep to effectively trap ions while minimizing the selected frequency's circular frequency oscillation amplitude. Is preferable. One or more actuation techniques are used to achieve these goals, and the preferred method depends on the particular mass spectrometry performed. When it is desired to select multiple mass-to-charge ions simultaneously, work along the Au = 0 or RF-only line to add multiple notch resonant frequency waveforms to the quadrupole and to select unselected ions m / z It is preferable to provide a value of a circular or resonant frequency excitation radiation. When selecting or isolating only one mass-to-charge value ion, in addition to adding a single notch resonant frequency waveform, a small amplitude + /
It is preferred that -DC be added to the quadrupole to provide a non-selective ion m / z value of the scalar frequency excited ion emission. Increasing the +/- DC amplitude reduces the radial trapping energy well depth to the desired ion, but reduces the range of required secular frequencies to reduce unselected, lower and higher mass to charge value ions. Provides an effective means for removal. An example of the operation of a hybrid TOF as shown in FIG. 1 in MS / MSM mode with a single mass-to-charge value ion selection using the method according to the invention is described below.

The multiple quadrupole assembly 8 composed of a hybrid TOF as shown in FIG. 1 operates in MS / MSM mode with a continuous ion beam supplied into section 1 of the quadrupole assembly 60. The selection of ion mass versus charge changes the amplitude of the RF potential during repetitive ion trapping and release operations, while adding +/- DC and a single notch resonant frequency waveform to produce a quadrupole assembly 60. Within the category 2 of DC accelerated CID fragmentation of selected ions is performed by acceleration of ions from section 2 of quadrupole assembly 60 through quadrupole assembly 61 and into quadrupole assembly 62. The quadrupole assembly 62 operates in a trap and release mode as taught in US Pat. No. 5,689,111, and mass-to-charge analysis of fragmented ions is performed in the TOF mass spectrometer 40. FIG. 3 shows the potentials acting on the multiple quadrupole assembly 8 and the TOF pulsing region 37 during MS / MS analysis. Section 1 of the four-pole assembly 60 operates in an RF-only mode. Referring to FIG. 3, different DC potentials acting on the capillary outlet electrode 112 and the skimmer 26, and different DC potentials acting on the poles of sections 1 and 2 of the quadrupole assembly 60 and pole 4 of the quadrupole assembly 62. The offset potential remains fixed during the MS / MS operation. The capillary for the skimmer potential is set to maximize the target ion propagation efficiency without causing DC accelerated CID spallation in the capillary to the skimmer region. The DC offset potential acting on sections 1 and 2 of the quadrupole assembly 60 will cause the ions to move from section 1 to section 2
Is set to propagate effectively without CID crushing. Due to the collisional damping of the ion kinetic energy in sections 1 and 2, the energy of the parent ion beam is determined by the DC offset potential of section 2. The frequency and amplitude of the RF potential acting on sections 1 and 2 of quadrupole assembly 60 are within the stability diagram 102 and β _y = 0, β _x = 1
Is set to maintain radial ion trap operation for ion mass to charge value wells selected far from the stable region boundary. The DC potential synthesis curve 143 shows the DC offset potential acting on the quadrupole assemblies 61 and 62 during the ion propagation mode. The different DC values of the DC offset potentials 146, 147 and 148 acting on the poles of section 2 of the quadrupole assembly 1, quadrupole 61 and quadrupole 62 are DC acceleration CIDs of the ions accelerated into the quadrupole assembly 62, respectively. Areas 107 and 110 sufficient to cause fracturing
A DC accelerating electric field is created inside. The selected ion DC acceleration collision energy is 4
It is set by the relative DC offset potential acting on the poles of section 2 of pole assembly 60, 4-pole 61 and 4-pole 62. The ion internal energy selected is the DC electric field at point 109 between points 114 and 127 in the capillary, between points 127 and 109, or between points 1 and 2 of quadrupole assembly 60 to the skimmer region. Is increased prior to acceleration into the four-pole assembly 62. The internal energy of the selected ion is also increased by some resonance frequency excitation within quadrupole 60 section 2 during ion mass versus charge selection. Increasing the mass-to-charge internal energy of the ions selected prior to acceleration into the quadrupole assembly 62 reduces the amount of DC acceleration energy required for ion fragmentation.

The quadrupole assembly 62 operates in an RF-only mode that is set to maximize the ion trap and propagation efficiency for the relevant fragment ion mass-to-charge values. For example,
When the ions selected within the quadrupole assembly 60 are multiply charged, the mass-to-charge of some debris ions will be higher than the selected source beam. The mass-to-charge of all fragment ions to simple charged ions selected in quadrupole assembly 60 will be lower than the source beam. When crushing the multiply charged ions, the pole 4 of the quadrupole assembly 62
The amplitude of the RF potential acting on the ion is set to a higher value when disrupting easily charged ions of similar mass-to-charge value. The RF potential acting on the rods of the quadrupole set 62 is low, unlike the high m / z which is blocked for low m / z value ions inherent in resonant frequency excited CID spallation as is done in a three-dimensional ion trap. Allows m / z value ions to stay in a stable orbit. The amplitude of the RF potential acting on pole 3 of quadrupole assembly 61 operating in RF-only mode is applied to quadrupole assemblies 60 and 62 to minimize fringing field effects at mutual quadrupole junctions 7 and 10. It is set so as to fall between the set RF amplitude values. The aligned, RF potential acting poles of the four pole assemblies 60, 61 and 62 have the same frequency and phase to minimize fringing field effects at junctions 6, 7 and 10. The DC waveform 143 indicates that the DC potential acting on the lenses 33, 34, 35, 41 and 42 is set to allow ion propagation into the TOF pulsed region 37. In particular, the potential 151 acting on the lens 41 is set near the ground potential. The electric field between points 11, 13, 134, 135 and 141 is set in the TOF pulsing region 37 to optimize beam energy in terms of energy and shape. DC curve 143 corresponds to point 153 which is drawn through timing diagram 156 shown in FIG.

The background pressure in the inlet end 71 of the quadrupole assembly 62 is first applied as a collision gas for DC accelerated CID ion fragmentation and then to the host and debris ion populations traversing the length of the quadrupole assembly 62. , Acts as an ion kinetic energy damping gas. The DC potential acting to exit lens 33 serves to trap and release ions from exit end 11 of quadrupole assembly 62. Trapped ions are released or gated from the exit end 11 of the quadrupole assembly 62 into the TOF pulsing region 37 which pulses them into the TOF floating region 58 and mass-charge analyzes. An ion trap within quadrupole assembly 62 allows ions to select multiple paths back and forth through the length of quadrupole assembly 62 before leaving the gate. The trapped ions enter the entry end 7 of the quadrupole assembly 62
Back to 1 they are the entrance ends 71 where impact kinetic energy damping occurs.
It passes through the high-pressure background gas inside. Even for high energy ion acceleration into the quadrupole assembly 62 sufficient to cause CID spallation, the diffusion of the resulting fragment ion kinetic energy is attenuated and the quadrupole ion guide shuts off thermal energy diffusion. A monoenergetic ion population is created in the assembly 62. The average potential energy of ions traversing quadrupole assembly 62 is determined by the DC offset potential acting on pole 4 of quadrupole assembly 62. The background pressure in the third vacuum step 73 is maintained below the 10 ^-5 Torr range, so that ions exiting the quadrupole assembly 62 through the outlet end 11 have a TOF
When moving into the pulsed region 37, it no longer collides with the background gas. Ion-molecule collisions in this region result in scattering and defocusing of the ion beam traveling into the TOF pulsed region 37, degrading TOF performance.

To select the mass versus charge in section 2 of quadrupole assembly 60, the amplitude of the resonant or secular frequency waveform +/− DC potential, RF and the mixture of rods of quadrupole assembly 60,
Acts on Category 2. The +/- DC potential, RF and sucular frequency waveforms that act over time are shown in potential curves 137, 138 and 136 in timing diagram 156, respectively. Within the resonance waveform 136, the amplitude, phase and frequency components of each circular frequency remain constant during ion mass versus charge selection within section 2 of the quadrupole assembly 60. The frequency and amplitude components of the working circular frequency waveform 136 include a number of auxiliary ranges described by US Pat. No. 5,521,380 for mass to charge in a three-dimensional quadrupole ion trap. Creating multiple auxiliary range sets of cellular frequencies combined with modulation of RF amplitude minimizes the number of cellular frequency components required to emit unselected ion m / z values, and reduces single or multiple ion mass versus During charge selection, ion losses selected from resonance frequency excitation are minimized. The interval between the frequency resonance frequency components remains within the auxiliary range. The frequency notch is maintained around the selected ion mass versus charge value and the amplitude of the frequency component at the frequency notch side or with a gap taper within the amplitude as the frequency approaches the selected mass to charge notch. . The RF amplitude is ramped as ions traversing section 2 of quadrupole assembly 60 (r
amp) to effectively change the resonance frequency for a given ion mass versus charge value. When approaching the resonance frequency of the selected ion from a lower or higher resonance frequency, the RF amplitude ramp waveform as shown by curve 138 is asymmetric, taking into account the asymmetry of energy storage from the resonance frequency. . This asymmetry is due to the action of higher pole field components within section 2 of quadrupole assembly 60 during ion mass versus charge selection or isolation operation. The ramping of the RF amplitude allows control over how long the selected ion is consumed, which is unique to section 2 of the quadrupole assembly 60 and is exposed to near resonance frequencies. Higher resolution mass-to-charge selection with minimal loss to the desired ion is obtained with careful selection of the frequency, phase and amplitude components of the resonant or secular composite waveform combined with the best RF amplitude ramping.

As the ion population of interest spends more time inherent in section 2, higher resolution mass-to-charge selection may be applied to section 2 rods of quadrupole assembly 60 as described above. With a strong electric field. Increasing the exposure of non-selective mass-to-charge value ions to more RF and resonance frequency cycles can be achieved with a four-pole assembly 60 in the presence of background gas.
To improve the efficiency of unselected ion emission from category 2 of The same background gas
With respect to the center line 5 of the quadrupole assembly 60, the radial vibration of the selected non-excited ions is effectively damped. D of ions attenuated relative to centerline 5 into quadrupole assembly 62
C-acceleration minimizes scattering losses of host and debris ions. In order to increase the ion residence time selected in section 2 of quadrupole assembly 60, ions may be trapped in section 2 or alter the offset potential acting on the rods of quadrupole assembly 61. , To be released from there repeatedly. Any effect of the space charge on the resonance frequency of the selected ion can be minimized or eliminated by selecting an appropriate fill and dispense cycle period. Curve 1
39, 140 and 142 show examples of ion trap and release timing in quadrupole assemblies 60 and 62 synchronized by TOF pulsed voltage acting on lens 41. Curve 139 shows the offset potential acting on bar 3 of quadrupole assembly 61 during MS / MS operation. When applying the offset potential 148, the ions are moved to the quadrupole assembly 60.
Trapped in section 2 of The ions are released from section 2 and the quadrupole assembly 6
Accelerated with sufficient energy through quadrupole 1 into quadrupole assembly 62 to cause CID pulse spallation when applying DC offset potential 147 to rod 3 of quadrupole assembly 61. When increasing the DC offset trap potential acting on the four-pole assembly 61,
The provisional voltage 149 is applied to the quadrupole assembly 62 above the offset potential acting on the rods of section 2.
Without increasing the kinetic energy of the ions accelerated into the quadrupole assembly 61
Act for a short time to remove ions from the volume. DC offset potential 149 is set to a value just above the offset potential of section 2 to prevent ions from entering quadrupole assembly 61 while ions in quadrupole assembly 61 enter quadrupole assembly 62. Allow to be accelerated. The ions in the volume of the quadrupole assembly 61 have a DC offset potential of 15
When adding 8, some may return to Category 2, which does not fragment. 4 if desired
The offset potential applied to the poles of pole assembly 61 adds the proper timing and voltage amplitude to the trap and release DC offset potentials into front four pole assembly 62 or back four pole assembly 60. To increase the potential energy of the ions that are accelerated. This increase in pulsed ion kinetic energy is similar to the backward DC accelerated CID ion spallation described in US patent application Ser. No. 08 / 694,542 using switching potentials acting on lenses 33 and 34.

The switching of the DC offset voltage of the four-pole assembly 61 is performed by pulsing the TOF ions in the TOF floating region 58 and ionizing the ions so that the switching of the voltage does not occur during the flight time of the ions in the TOF floating region 58. Synchronized by flight time. This avoids electrical noise peaks from occurring in the acquired mass spectrum.
The DC potential curve 144 occurs on a time line 144 that is drawn through the timing diagram 156. The DC voltage curve 144 acts on the quadrupole assembly 61 and the rod of the lens 3, respectively, while the DC potential 152 acting on the TOF pulsed lens 41 rises and accelerates ions to the TOF floating region 58. And 150 are shown. TOF
Mass spectrometry is performed on ions that are pulsed into the TOF floating region 58. TOF
The trapping and release of ions from the quadrupole ion guide assembly 62 following mass spectrometry is described in US Pat. No. 5,689,111. MS / MS analysis is performed by switching the sequence using the addition of RF, SF and DC potentials, and using high efficiency ion mass vs. charge selection and DC accelerated CID fragmentation, as described above. The MS / MS sequence is a small multiplex 4 configured with a TOF mass spectrometer.
This is done using a pole assembly. An alternative method is to use the effective M
Used to obtain S / MS analysis. For example, the resonant frequency waveform 136 has been removed and has a higher +/- DC amplitude acting on the bar of section 2. The amplitude of the repetitive ramping of the RF is set to move the selected ion m / z value back and forth across the stability diagram 102 so that the m / z value is stable at β _y = 0 and β _x = 1. Minimize time spent near region boundaries. In this technique, ion mass to charge value ions above and below the selected m / z ion are emitted from the quadrupole, while providing minimal excitation energy to the selected ion. Alternatively, the excitation resonance frequency acts on a bar of the quadrupole assembly 62 that is matched to the host ion m / z value selected to selectively assist in fragmentation of the host ion. Quadrupole assemblies 60 and 62 may also operate in a single ion non-trap mode. Additional techniques for performing MS / MS ⁿ analysis function will be described below.

The optimization of the RF, SF and DC potentials and the potentials acting on the poles of the multiple quadrupole assembly 8
The sequence of switching and ramping is performed by a second vacuum pumping process as shown in FIG.
This is done by the background pressure maintained in step 72. The collision between background gas and ions is
Resulting in desired and undesired fracturing, increasing the time of unstable orbits of ion radiation,
Decrease stable ion orbit to quadrupole center line and reduce ion transit time through quadrupole length
And to provide a reaction medium to ions for studying the reaction of the neutral gas phase. High background pressure
The greater the number of ions generated per hour to neutral gas collisions, the greater. Appropriate
The size of the skimmer hole 27 and the appropriate vacuum pumping speed through the vacuum port 29
By configuration, the background pressure in the second vacuum pumping step 72 is 1 × 10 ^-Four It can vary between torr and 500 mTorr. Numerous operations described below
For a sequence, the background pressure is determined by the ion and the ion as it traverses each quadrupole length.
It should be maintained in a vacuum step 72 where multiple collisions between background gases occur. flat
The uniform free path results in effective stable ion orbital decay, effective DC acceleration and resonant frequency
Although several-excitation CID ion fragmentation occurs, orbital decay is limited within an experimentally useful time frame.
It should be kept in equilibrium without blocking the emission of ions in unstable orbits. Typical
Typically, a background pressure of between 4 and 8 mTorr is maintained during operation in the vacuum step 72.
You. The gas component is nitrogen with only a background gas supply from an atmospheric pressure ion source.
is there. Background gas components are introduced into a vacuum step 72 as in the embodiment of the invention shown in FIG.
It can be changed by adding a secondary gas such as helium or argon. Anti
Reaction gas may be added to vacuum step 72 to study the reaction of ions with neutral gas.
No. In one embodiment of the invention, the multiple quadrupole assembly 8 has a 1.25 mm r.₀Composed of
And operates at an RF frequency of about 5 MHz.

Best Background Vacuum pressure and gas composition are based on multiple ion guides including pole-to-pole spacing, individual section or quadrupole assembly lengths, and the range of MS / MS ⁿ functions required to perform the device. It is a function of the shape. For discussion purposes, it is assumed that the background pressure in the second vacuum step 72 is maintained at a pressure between 1 and 10 mTorr. 1-10 mTorr is a typical operating pressure found in a triple quadrupole three dimensional quadrupole trap and quadrupole ion guided collision chamber. The background gas in the three-dimensional ion trap is typically helium, and the background gas introduced into the triple quadrupole collision chamber is typically argon. The gas load in the second vacuum step 72 mainly consists of the backflow dry gas 21 from the ES source 12. The countercurrent dry gas 21 is typically nitrogen, but may include carbon dioxide, sulfur hexafluoride, oxygen and residual solvents from the sample solution, depending on the analytical application. The pressure and composition of the background gas in the second vacuum step 72 is controlled and kept constant during the MS operation to optimize the working potential. ES source 12
Is maintained close to the atmospheric pressure, and the temperature in the capillary hole 57 is MS
Since the operation is in a steady state, the dense gas flux through the capillary holes 57 is consistent with the MS operation. In the embodiment shown in FIG. 1, the skimmer hole 27 is typically located inside the supersonic free injection zone, typically upstream of impactless silence. As a result, the second vacuum step 72
The gas flux into is harmonic over time during the MS operation. Second vacuum step 72
The pressure match within is primarily determined by the vacuum pumping speed through the vacuum port 29. The use of a turbo molecular vacuum pump to evacuate the second step 72 provides a consistent pumping rate over an extended period of time. Turbo molecular pump RP
Due to the ability to monitor M and the direct measurement of the background vacuum pressure in the vacuum step 72, the background pressure is kept constant for an extended time. Harmonic components and pressures to the neutral background gas in the second vacuum step 72 provide reproducible results for a wide range of experimental sequences to be performed.

The background pressure of the ions in the second vacuum step 72 is high enough to be used for fragmentation by the CID step, but the m / z selection performance or ion propagation efficiency is compromised. Not as high. The configuration of the segmented multipole ion guide 8 combined with the TOF mass spectrometry shown in FIG. 1 is a triple quadrupole all MS and MS / MS function and a three dimensional ion trap all MS and MS / MS ⁿ function sequence. considering implementation of a, and can not either triple quadrupole or a three-dimensional quadrupole ion trap, it is possible to carry out the several MS and MS / MS ⁿ function. Hybrid T shown in FIG.
Some examples of possible MS / MS ⁿ function in OF embodiment will be described below.

A four non-trap single pass primary MS / MS mode of operation is used in a triple quadrupole using DC ion acceleration into an RF only collision chamber to obtain CID fragmentation. These four modes of operation include: 1. A single selected m / z propagation within the quadrupole 1 that scans the quadrupole 3 while disrupting the selected ions in the RF-only collision chamber. 2. The four poles 1 and 3 have a fixed m /
Neutral loss scan scanned simultaneously with z offset. 3. Setting the four poles 3 to scan the four poles 1 while passing through the selected m / z range with fragmentation of the host ions in the RF only collision chamber. 4. Setting of the four poles 1 and 3 to pass different m / z values without scanning with disruption of the host ions in the RF-only collision chamber to monitor the selected result.

In the embodiment of the hybrid TOF shown in FIG. 1, the complete fragment ion spectrum is
Without scanning, which results in higher sensitivity and resolution performance than can be obtained with triple quadrupole operation, TO
Recorded in the F analyzer. The hybrid TOFMS as shown in FIG.
Instead of pole-single mass selection and mass scanning analysis functions, it works to mimic triple quadrupole performance with the complete TOF mass spectrum acquired. MS / MS requires the steps of mass-to-charge selection, disruption of the selected mass-to-charge parent ion, and mass analysis of the first generated fragment or product ion. The final mass-to-charge selection step in any given MS / MS sequence is performed in the mass spectrometer 40. The mass-to-charge selection and ion fragmentation steps are performed in a multiple quadrupole assembly ion guide 8 with additional ion fragmentation performed in the capillary to the skimmer region when needed. An MS / MS experimental sequence as described in the previous section was performed, which
Produces fragmented ions similar to those created in polar MS / MS operating mode 1. Alternatively, using a different experimental sequence, the debris ion population is
Produces analogs to those made in S / MS experiments.

The hybrid multiplexed quadrupole TOF as shown in FIG. 1 scans the quadrupoles 4 and 3 during data acquisition, the triple quadrupole neutral loss MS / MS operating mode 2 as described above.
Act to simulate TOF operation, which replaces the 4-pole 3 scan, produces a complete TOF spectrum of debris ions. A reconfigured ion chromatograph (RIC) is created from a fully acquired TOF spectrum and adapts to a triple quadrupole, as well as neutral loss MS / MS data. To obtain this auxiliary set of neutral loss data, the hybrid multiple quadrupole TOF embodiment shown in FIG. 1 can operate as follows. 1. Section 1 of the quadrupole assembly 60 operates in a non-trapped RF-only mode with an additional DC offset potential that allows ions to pass into section 2 at low energy without CID spalling. 2. Section 2 of the four-pole assembly 60 includes modulated RF, +/- D as described in the previous section.
It operates in the non-trapped ion m / z selection mode with the addition of C and the appropriate synthetic resonance frequency waveform. To simulate the first quadrupole scan of a triple quadrupole mass spectrometer,
Periodically advance the m / z selection window of section 2 to a new value until the desired m / z range is covered. The Category 1 m / z window stroke is synchronized with the TOF spectral acquisition so that any given first generation fragment maternal ion mass versus charge is known. 3. Section 3 operates in a trap RF only mode. The different DC offset potentials acting on the poles of section 2 of quadrupoles 60, 4 and 61 and 62 are accelerated with sufficient energy from section 2 into quadrupole 62 to select the desired amount of CID ion spallation. It is set to originate from parent ions. Ions released or gated from the exit end of the quadrupole 62 and traveling into the TOF pulsing region 37 are pulsed into the TOF floating region 58 and mass analyzed.

Consider a neutral loss scan over a host mass to charge range from 400 to 800. 4 m / z where the maternal 4-pole m / z window is selected by section 2 of assembly 60
, Then 100 strokes are needed to cover m / z from 400 to 800. As the TOF mass spectrometer is pulsed at a rate of 10,000 times per second, with 1,000 pulses acting on each mass spectrum stored for storage, 10 mass spectra per second are recorded. Under these TOF data acquisition conditions, a fully simulated neutral loss scan takes 10 seconds to acquire. TO
If the F spectrum is obtained at a rate of 40 spectra per second, the total acquisition time to each fully simulated neutral loss scan is close to the typical scan speed used in a triple quadrupole neutral loss scan. 5 seconds. The TOF full spectrum data obtained in the above scanning sequence differs from the limiting information recorded from a triple quadrupole neutral loss scan or when the first quadrupole is scanned with a fixed third quadrupole m / z range selection. , Including completely crushed ion information. Consequently, any triple quadrupole experiment is simulated with the segmented ion guided TOF operating sequence described above. The changes in the above sequence can be used to achieve the same purpose. For example, m / z range selection is performed in section 1 or sections 1 and 2 of quadrupole assembly 60 in trapped or non-trap mode.
Quadrupole ion guide assembly 62 operates in a trapped or non-trapped mode. The trap voltage acting on the lens 33 in the trap mode is kept low when switching the m / z range within the quadrupole 60 section 1 or 2. At that time, the trapped ion debris formed from the preceding parental m / z value will exit the trap formed by the quadrupole 62. Prior to the restart of the TOF pulsing, a small delay time is introduced after the step of selecting the m / z range in which to fill the traps in section 4. Alternatively, host ions are trapped in section 2 of ion guide 60, while debris ions from the preceding host mass-to-charge value are gated from quadrupole 62 into TOF pulsed region 37. The selected host ions of m / z trapped in section 2 are accelerated into quadrupole 62 after fragment ions from the preceding host ion set are gated into TOF pulsed region 37. The new set of mass-to-charge values of the parent ion is then insulated within quadrupole 60 section 2. When the DC offset potential acting on the poles of the quadrupole 61 is different from the sub-ion population, the movement of all ions trapped inside section 2 releases, as described in the preceding section. However, the continuous ion beam is accelerated into section 1 of quadrupole assembly 60 in either mode of operation to maximize overall utilization.

In the simulated triple quadrupole neutral loss scanning mode of operation described above, DC ion acceleration is used to obtain CID first generation ion spallation. Alternatively, resonant frequency excited CID fragmentation is used with quadrupole assemblies 61 and 62 or a combination of DC ion acceleration and resonant frequency excitation. The preferred disruption technique depends on the analytical information desired. Resonant frequency excitation is used to disrupt selected ions, especially splintered product ions, to a non-selected m / z value without additional internal energy. Due to the multiple collisions experienced by all ions created by the DC ion accelerated CID, the internal energy of all accelerated ions increases, including that of spalled ions created. Resonant frequency excitation has the disadvantage that the amplitude of the resonant frequency is increased due to the increased fracture energy. To trap the excited ions in the radial direction,
The RF amplitude must increase proportionally, resulting in a low m / z cutoff. Typically, when operating the ion trap in MS / MS mode, more than one third of the bottom of the m / z scale is emitted to provide sufficient resonant frequency excitation spallation of the relevant host ions. Both DC ion acceleration and the resonance frequency excitation is combined simultaneously or sequentially, without emitting a lower portion of the mass-to-charge scale, the best MS / MS or MS / MS ⁿ performance obtained. Hybrid partitioning ion guide TOF embodiment shown in Figure 1, all of the triple quadrupole as described above, and an ion trap MS / MS ⁿ function, and DC acceleration, either triple quadrupole or ion trap line It is configured to be obtained in combination with an unresonant resonance frequency excited CID ion breaking operation.

A wide range of MS / MS ⁿ analysis functions are performed using the hybrid TOF embodiment shown in FIG. To simplify the description of the actuation sequence necessary to perform the individual MS / MS ⁿ function, using techniques are divided into two groups. The first group is
Some require the cutting of a continuous ion source that produces a primary ion beam,
And those that do not require interruption in the primary ion beam. From electrospray ion source 12 first receiving continuous ion beam, a number of MS / MS ⁿ techniques, is described below.

Consider the operation of the MS / MS ² experiment with the embodiment shown in FIG. The simplest functional sequence is an extension of the MS / MS case described above where DC accelerated ion fragmentation occurs between sections 1 and 2 of quadrupole assembly 60. In particular, hybrid multiple quadrupole TOF
Operates in the following sequence to obtain MS / MS ² mass spectrometry. 1. Section 1 of quadrupole assembly 60 operates in a mass-to-charge selection mode. The selected mass-to-charge ions are accelerated into section 2 with a sufficient DC offset potential acting between sections 1 and 2, resulting in CID ion spallation of the selected ion at m / z. 2. Section 2 of quadrupole set 60 operates in a trapped or non-trapped mass-to-charge selection mode that selects one or more first generation product ions. Thereafter, the selected first generation product ions of m / z are accelerated through the four poles 61 and into the four poles 62, and the appropriate relative DC offset potential is applied to the poles of section 2 and the four poles 61 and 62. This results in CID fragmentation of the selected first generation fragment ions. 3. The quadrupole 62 operates in an RF-only trap mode that gates second generation crushed ions into the TOF pulsing region 37. Subsequently, the second generation crushed ions were converted to T
Pulse into the OF floating region 58 and analyze mass versus charge.

The ion mass-to-charge selection operation within segment 1 and 2 of quadrupole assembly 60 can be achieved by modulating RF and +/− DC mass filtration of undesired m / z ions, or a composite resonance frequency as described above. Use waveform emission or a combination of both. Different RF and + /
-DC, the combined resonance frequency waveform AC potential, and the common RF potential at the same time
And 2 are added to the pole. Ion crushing is carried out within the division 2 of 4 poles 60 and 4 poles 61 and 62.
It is obtained using a resonance frequency waveform instead of or in conjunction with accelerated C ion spallation. Resonant frequency excitation occurs simultaneously with ion m / z selection in section 2 of quadrupole assembly 60 by including appropriate frequency notches and amplitude changes in the composite resonance frequency waveform acting on section 2 poles. it can. Section 2 adds an appropriate relative DC offset potential to the poles of quadrupole assembly 61 to trap ions within section 2 of quadrupole assembly 60 or to move ions from section 2 to quadrupole assembly. Release in 62 operates in trap mode. In all MS / MS ⁿ experiments, the relative potential of the capillary to the skimmer increases and increases the internal energy of the ions in the primary ion beam, facilitating fragmentation in the multiple quadrupole ion guide assembly 8. .

MS / MS ² is obtained by operating the multiple quadrupole ion guide assembly 8 in the following mode, alternatively mixing DC ion acceleration and resonance frequency excited ion fragmentation techniques. 1. Section 1 of quadrupole assembly 60 operates in an RF-only ion propagation mode. Ions move from section 1 to section 2 at low energy and without ion fragmentation. 2. Section 2 of quadrupole assembly 60 operates in trap mode with ion mass versus charge selection. When released from section 2, ions are accelerated from section 2 with sufficient energy through quadrupole 61 and into quadrupole 62, resulting in CID fragmentation of the selected ion at m / z. 3. The quadrupole assembly 62 operates in ion trap mode with two stage m / z selection of the first generation ions selected and resonant frequency excitation spallation. Second generation debris or product ions are gated into the TOF pulsed region 37, followed by a mass
F is analyzed. The m / z selection and ion CID crushing steps are performed continuously prior to the start of TOF mass spectrometry. The host ions are trapped and accumulated in segment 2 during the first generation ion m / z isolation and crushing process performed in quadrupole assembly 62. After releasing the second generation debris ion population from quadrupole 62 and analyzing the TOF mass versus charge,
A new set of selected mass-to-charge value ions is accelerated into quadrupole 62. The new first generation fragment ion population is trapped in quadrupole 62 and undertakes sequential mass to charge isolation, ion fragmentation and TOF mass spectrometry steps.

The quasi-MS / MS ⁿ experiments are obtained with a continuous primary ion beam using the techniques described in US patent application Ser. No. 08,694,542. In this technique, no true m / z selection is made prior to ion fragmentation. Instead of two spectra, the first one is obtained in succession with a combination of host or splintered ions, and the second with the next generation splinter ions. The first TOF mass spectrum obtained is MS
/ MS ⁿ extracted from the second to give the spectrum containing the peak of the fragment ions. This method requires a multi-component resonant frequency excitation waveform to perform CID excited ion fragmentation. Using this technique, MS / MS ⁴ experiments are performed on the hybrid quadrupole TOF shown in FIG. 1 as described below.

The mass spectrum 1 is obtained with the following operating sequence performed with the multiple quadrupole ion guide assembly 8. 1. Section 1 of quadrupole assembly 60 operates in a mass-to-charge selection mode. The generated ion population is accelerated with sufficient energy into section 2 resulting in CID spallation. 2. Binary resonant frequency excitation is applied to the poles of section 2 to induce CID fragmentation of selected second and third generation ions. Product ions pass through quadrupole assembly 61 and into quadrupole assembly 62 without further disruption. 3. Quadrupole assembly 62 operates in a trapped or non-trapped RF only mode with ions traveling into TOF pulsed region 37. The ions are subsequently pulsed into the floating region 58 of the TOF mass spectrometer 40 and mass to charge is analyzed.

The second TOF mass spectrum is generated with a ternary resonance frequency excitation acting on section 2 or a single resonance excitation frequency acting on pole 4 of quadrupole assembly 62 and has a consistent resonance excitation frequency Crush third-generation product ions, selected. The resulting first mass spectrum is extracted from a second mass spectrum that yields a mass spectrum that includes fourth generation spallation or product ions and their individual parent ions.

An alternative MS / MS ⁿ analysis technique using a continuous or discontinuous primary ion beam, depending on the particular analytical application, is used. With this technique, ions move from one section or quadrupole assembly to an adjacent section or quadrupole assembly in a block. All ions trapped in one section or quadrupole travel to the next continuous section or quadrupole ion guide assembly before approaching a new population of ions from the previous section or quadrupole assembly. Each segment or quadrupole assembly is independently single or multiple m / z as ions move between segments or quadrupole assemblies.
The selection and / or resonance frequency excitation CID ion fragmentation function can be performed, or the ions are fragmented using DC accelerated CID. MS / MS ³ using this technology
The steps of the analysis are described below. 1. Section 1 of quadrupole assembly 60 operates in RF-only mode with ion m / z selection or isolation using multi-frequency composite waveform resonance frequency emission of unwanted ions. The relative DC offset potential acting on the poles of sections 1 and 2 of quadrupole assembly 60 is such that ions from section 1 are accelerated into section 2 with sufficient kinetic energy to provide DC
It is set to cause accelerated CID ion fragmentation. The primary beam is always emitted and the ions continuously enter section 1. 2. The relative DC offset potential acting on the rods of section 2 of quadrupole assembly 60 is:
It is set to trap ions in section 2 for a given time. Section 2 operates in m / z selection mode, and the first generation crushed ions of the selected m / z value are:
Trapped in Section 2 for a given time. 3. The DC offset potential acting on the rod 3 of the quadrupole assembly 61 is then of sufficient duration to make the section 2 of the ions trapped to the level of a continuous primary ion beam operating in single pass mode substantially empty. During this time, it is switched low to pass ions from section 2 of quadrupole assembly 60 through quadrupole 61 and into quadrupole 62. The ions are accelerated from section 2 of quadrupole assembly 60 through quadrupole 61 into quadrupole 62 with sufficient kinetic energy to produce DC accelerated CID ion spallation. After the ions have traveled through the cycle, the DC offset potential acting on pole 3 of quadrupole 61 is switched high to trap ions in section 2 and trapped ions in opposite direction of quadrupole assembly 60. The quadrupole 42 is prevented from re-entering section 2. 4. The quadrupole assembly 62 is initially configured so that the ions pass through quadrupole 61 from section 2
While moving into 2, it operates in m / z value selection mode. The potential acting on lens 33 is initially set to trap and hold ions in quadrupole assembly 62. After the DC offset potential acting on pole 3 of quadrupole assembly 61 has been raised to stop ion flow from section 2 of quadrupole assembly 60, the potential acting on pole 4 of quadrupole assembly 62 is: The quadrupole 62 is switched to operate in RF-only mode with resonant frequency excited CID spalling of the second generation spalled ions trapped within the quadrupole 62 at the selected m / z value. When the MS / MS ³ experiment is desired, the evolving, third generation product or debris ions trapped in the quadrupole 62 will switch within the gated ion peak by switching the voltage applied to the lens 33. Released into the TOF pulsing region 37 and the TOF is subsequently analyzed. Higher order MS / M
When an ^Sn step is required, an additional continuous m / z selection and CID fragmentation step is performed with ions trapped in the open quadrupole assembly 62 prior to release of the ions into the TOF pulsed region 37. You can continue. The TOF spectrum of a part of the product ion is
Obtained at each MS / MS step or at the end of the MS / MS ⁿ sequence. MS /
The MS process is performed with ions trapped in quadrupole assembly 62 while selected first generation product ions continue to accumulate in section 2 of quadrupole assembly 60. 5. All n-generation product ions trapped in quadrupole assembly 62 are
When gating into the pulsed region 37 and subsequently into the TOF mass to be analyzed, the DC offset potential acting on the pole 3 of the quadrupole assembly 61 is reduced and the process 3
And 4 are repeated.

The MS / MS ⁿ analysis function works with a discontinuous primary ion beam,
Can be operated using the hybrid TOF shown in FIG. Some features sequences are possible multiple quadrupole assembly 8 and TOF mass spectrometer 40 to perform the MS / MS ⁿ analysis by non-continuous primary ion beam. US Patent Application 08 / 684,5
42 describes the configuration of a multiple ion guide TOF mass spectrometer, where multipole ion guide operates in trap mode prior to TOF mass spectrometry with sequential m / z ion selection and resonant frequency excited CID ion fragmentation steps. I do. The addition of multiple sections and additional quadrupole assemblies constructed within the high background pressure region is useful when performing MS / MS ⁿ mass spectrometry sequences in a single section two-dimensional trap TOF with a discontinuous primary ion beam. Allows for impossible operation and analytical variations. Unlike a three-dimensional ion trap or FTMS mass spectrometer, the hybrid multi-quadrupole TOF configuration is designed to obtain MS / MS ⁿ functionality with higher energy DC accelerated ion fragmentation at each ion m / z selection and fragmentation step. Configured and works. Alternatively,
The multiple quadrupole ion guide assembly 8 is configured to perform resonance frequency excitation disruption or a combination of both CID disruption techniques during MS / MS ⁿ experiments to optimize performance for a given mass spectrometry. An example of an MS / MS ⁿ experiment performed by DC accelerated CID ion fragmentation using the multiple quadrupole ion guided TOF hybrid shown in FIG. 1 will be described below. 1. Section 1 of quadrupole assembly 60 operates in RF only non-mass selective mode with ions traveling into section 2 without fragmentation. 2. Section 2 of quadrupole assembly 60 operates in a trapped or non-trapped mass-to-charge selection mode, and the resulting ion population is accelerated through quadrupole 61 and into quadrupole assembly 62 with sufficient kinetic energy. CID fracture occurs. 3. The quadrupole ion guide 62 operates in a trap mass-to-charge selection mode and directs first generation debris ions of the selected m / z range into the pulsed region 37 with little or no ion gating. Gather in. The capillary relative to the potential acting on the skimmer 26 after the first generation debris ions of the selected m / z range are collected in the quadrupole 62 for a specific time or with occasional TOF monitoring of the ion population. Reducing the potential on the exit continuity 112 prevents the primary ion beam from entering the quadrupole assembly 60 of Section 1. Due to the delayed electric field acting on the skimmer region in the capillary, the ion exit capillary 23 is prevented from passing through the skimmer 27. 4. The ions trapped in the quadrupole ion guide 62 are then passed through the quadrupole ion guide 61 in the opposite direction by applying an appropriate relative DC offset potential to the rods of section 2, quadrupole 61 and quadrupole 62. And accelerates into section 2 of quadrupole assembly 60, causing CID fragmentation of the ions accelerated into section 2. Ions that are accelerated into Section 2 in the opposite direction, by increasing the relative DC bias potential of Sections 1 and 2,
Blocked from entering Category 1. If short MS / MS ⁿ analysis time is needed,
Ions are blocked from entering section 1 and reduce the time required to empty section 2 of ions at each MS / MS step. Alternatively, ions can enter section 1 as an extension of section 2 to increase the volume of section 1. Ions are blocked from entering the section 1 in the opposite direction through the inlet end 9 by applying a DC retarding electric field between the skimmer 26 and the section 1 pole. Collisions with neutral gas molecules from the free jet expansion that continue into the second vacuum step 72 through the skimmer 27 contribute to attenuating the reverse axial trajectory of the ions, and trapping the ions in the quadrupole assembly 60. Prevent it from being lost through the inlet end 9. Immediately before accepting the ion population from quadrupole 62,
And the potentials acting on the bars of section 1 are switched so that section 1 and section 2 operate in ion m / z selection mode. 5. The selected m / z range of second generation fragment ions is collected in section 2 of quadrupole assembly 60. The generation population of second generation fragment ions is re-accelerated through quadrupole ion guide 61 and into quadrupole ion guide 62 with sufficient kinetic energy to produce CID fragmentation of the selected second generation fragment ions. . 6. The interior of the quadrupole ion guide 62 operates again in the ion trap mode. If the experiment ends with third generation ions, the generated ion population in quadrupole 62 is subjected to TOF mass spectrometry. If MS / MS ³ or more n generation product ions are required, step 4 or step 4
And 5 are repeated to create MS / MS ⁿ generation fragments or ions and the like. The trapped ion population is sampled at each MS / MS step and subjected to TOF mass spectrometry to consume only a small amount of the trapped ion population. TOF mass spectrometry is performed after the last MS / MS ⁿ th step until the entire ion population is emptied from quadrupole 62 of multiquadrupole ion guide assembly 8. 7. The voltage on the capillary exit lens 11214 is increased to allow ions in the primary ion beam to pass again through the skimmer aperture 27 and to the quadrupole ion guide assembly 6.
0 into the section 1 of the inlet end 9. 8. Sequence steps 1 to 7 are repeated. The number of MS / MS ⁿ step something, constituting in this way with mass spectrometry.

MS utilizing a mixture of resonant frequency excited spallation and DC ion accelerated CID spallation
/ Another example of MS ⁿ analysis is described below. 1. Operating section 1 of the 4-pole assembly 60 in non-m / z select RF only mode,
Pass the ions into section 2 without CID disruption. 2. Section 2 is operated in a mass selective mode with traps and non-traps to pass selected m / z ions through quadrupole ion guide 61 and into quadrupole ion guide 62 without DC accelerated spallation. 3. The quadrupole ion guide 62 is operated in trap mode with resonant frequency excitation disruption of the selected host ion at m / z. A supplemental set of resonance frequencies is simultaneously added to prevent unwanted first generation fragment ions while maintaining selected first generation fragment m / z value ions. The internal energy of the first generation fragment ion selected for the m / z value increases in the quadrupole ion guide 62 during host ion CID fragmentation. The selected first generation fragment m / z value ions accumulate in the quadrupole 62 during a set time period or until the desired ion population density is reached and checked by short time TOF mass spectrometry. Is done. 4. When filling the quadrupole ion guide 62 to the desired ion density level, the primary ion beam is blocked from passing through the skimmer hole 27 by reducing the potential acting on the capillary exit electrode 112. 5. The selected first generation fragment ions are accelerated in a reverse direction from quadrupole ion guide 62 through quadrupole ion guide 61 and into section 2 of quadrupole ion guide 60 with sufficient kinetic energy to effect CID spallation. 6. Prior to receiving the first generation fragment ions and the second generation fragment ions, the potential acting on the poles of section 2 is switched to operate in mass versus charge selection mode to m / z selection of second generation fragment ions. Is switched. 7. If another MS / MS analysis sequence is desired, repeat steps 2-6.
If additional MS / MS steps are not desired, by moving the ions through the quadrupole assemblies 61 and 62 without further fragmentation, the desired ion population on the entire ion population trapped in section 2 of the quadrupole ion guide 60 Of TOF mass spectrometry. 8. Upon completing the TOF mass analysis and emptying the multiple quadrupole ion guide assembly 8, the primary ion beam again passes through the skimmer hole 27 and into section 1 of the quadrupole assembly 60. Repeat steps 1-7 to continue the data acquisition with MS / MS ⁿ analysis.

As described in US patent application Ser. No. 08 / 694,542, higher energy C
The outlet end 11 where the ID crushing is configured in the low pressure region of the third vacuum pumping step 73
By accelerating the ions back into the quadrupole ion guide 62. The potential of the ions gated into the gap between the lenses 33 and 34 is increased by rapidly increasing the voltage acting on the lenses 33 and 34. The potential acting on the lens 33 is then reduced to accelerate the ions back to the multiple quadrupole ion guide assembly 8. Opposite DC accelerated ions impinge on the background gas within the multiple quadrupole ion guide assembly 8 as they traverse the length of the multiple quadrupole assembly 8 or individual quadrupole assemblies 60, 61 and 62. I do. In a similar manner, a quadrupole ion guide 61 or a combination of quadrupole ion guides 61 and 62 reversely accelerates ions back into section 2 of quadrupole assembly 60 to abruptly increase the internal energy of the ion population. Used to However, the ion acceleration from the quadrupole ion guide assembly 61 is such that the background velocity of the resulting ion is lower than the velocity obtained by reversely accelerating the ions from the free collision zone at the ion guide exit end 1. Get up in the presence of. Unlike a three-dimensional ion trap or FTMS mass spectrometer operating in MS / MS ⁿ mass spectrometry mode, the multiple quadrupole ion guided TOF hybrid shown in FIG. 1 has a wider range of collision energies to obtain ion fragmentation at each MS / MS step. Can be supplied. Control of the MS / MS ⁿ function sequence is simplified with a programmable software function that calculates the resonance frequency waveform and controls the RF and DC potentials acting on each section and quadrupole assembly. A software command type controller 80 as shown in FIG. 2 transmits waveforms, amplitudes, switch timings, and other control information through control contacts 81, 77, 78, 79, 82 to DC, RF, SF, +/-. DC power supply and switch units 66, 63
, 64, 65, 67 respectively. Output contacts 85, 86, 68, 69, 7
0, 87, 75, 76, 88, 84 provide appropriate potentials to the capillary exit lens 112,
Skimmer 26, rod of multiple quadrupole assembly 8, exit lenses 33, 34, 35 and TO
These are added to the F-pulse lenses 41 and 42 respectively.

Rapid switching of the DC offset potential is performed by operating two individual DC power supplies that are set to the appropriate potential. The poles of each section or 4-pole assembly are connected via a +/- DC power supply and a set of corrugated generators. The primary side RF is connected to the individual R configured in the power supply units 63, 64, 65.
Acts directly on the poles of each 4-pole assembly through capacitive coupling from the F supply. The +/- DC potential is activated after coupling the RF coupling capacitance and the resonant frequency AC waveform individually into the RF coupling to the appropriate poles of each section of each quadrupole assembly. Alternatively, the resonant frequency AC waveform capacitively acts on at least two poles of each section of each quadrupole assembly. The state of each switch is controlled by a controller 80 from a computer program that synchronously changes the state of all switches required to change the device state. RF, S
The F, DC power supply amplitude is set by an interface such as a digital to analog converter using the same computer control program. Such computer control systems, MS / MS ⁿ experiments sequence, the switch is obtained by programming a set of control signals and delay pattern. The control sequence is selected by the user during operation based on preset values or based on data received, prior to programming the data acquisition operation and initiation of a state change. Data-dependent software control decisions are used, for example, to select and disrupt ions that contain a larger spectrum in the parent mass spectrum. The ions that result in the larger amplitude maternal peak detected for a given mass spectrum are then m / z selected and subsequently broken up in the programmed data in an automated software control sequence.

The quadrupole ion guide assembly 61 of the multiple quadrupole assembly 8 includes quadrupole ion guides 60 and 62
Helps to separate both electrically and functionally. Ions are classified in the quadrupole assembly 60
When the DC offset potential trapped in and acting on pole 3 of quadrupole ion guide 61 increases to the trapped ions and decreases to pass ions from section 2 into quadrupole ion guide 61, it is released. The multiple quadrupole assembly 8 is configured with a large number of sections per quadrupole assembly or with a large number of sections to obtain greater instrument flexibility resulting in a greater range of analytical capabilities. Device flexibility and some complexity are added by increasing the number of quadrupole assemblies and sections per multiquadrupole ion guide assembly 160 composed of hybrid quadrupole TOFs as shown in FIG. Increase to gain functionality. The multiple quadrupole ion guide assembly 160 includes four quadrupole assemblies 161-164. The two-section quadrupole assembly 161 has a symmetrical section 1
65 and an outlet section 166. The two section quadrupole assembly 162 includes a symmetric section 167 and an outlet section 168. The single section 4-pole assembly 163 is
9 and four section quadrupole assemblies 164 including sections 170-173. Each four-section quadrupole assembly bar has its output RF waveform connected to four independent RF power supplies having a common frequency and phase. The rods of each of the four quadrupole assemblies are connected to independent resonance, or sec- ondary frequency component waveform supplies. The rod in each section of each 4-pole assembly is connected to an independent DC offset or +/- DC voltage supply. Alternatively, a common RF supply is connected to all quadrupole assemblies 160 of the multi-quadrupole assembly 160 to reduce the analytical capacity slightly and reduce equipment cost and complexity. DC to individual 4-pole sections during operation when using a common RF supply
When changing the SF and the SF, care must be taken to separate the electric resistance. Inadvertent coupling of the rapidly switched DC potential into the RF potential results in rapid and undesirable ion emission from the quadrupole volume. A supplemental background gas is added through channel 178 into second vacuum pumping step 198 to modulate the background gas component in multiple quadrupole assembly 160. Valve 199 is connected to vacuum step 19 through channel 178.
8 to control the flow rate of the auxiliary gas. Helium is added to reduce the mass of the collision gas, argon is added to increase the mass of the collision gas, or the reactant gas acts on the neutral gas phase to look for ions. Each adjacent section of each quadrupole assembly and each adjacent quadrupole assembly is electrically isolated to isolate different potentials acting on the bars or poles of each adjacent section. 4-pole assembly 161,162,163,164
Are arranged sequentially along the center line. Multiple quadrupole assembly 160 is shown in a linear configuration. Alternatively, multiple quadrupole assembly 160 may include a four-pole assembly that includes curved bars or poles.
Configured with the pole assembly.

Compared to the configuration of the multiple quadrupole assembly 8 shown in FIG. 1, an effectively multiple, third independent quadrupole assembly 161 has been added to the multiple quadrupole assembly 160. An additional four-pole assembly 161 configured in the high background pressure region of the vacuum pumping step 198 comprises:
Allows for performing the crushing step with independent mass selection and / or ion trapping. The ions are independently applied to the quadrupole assembly 16 in the multiple quadrupole assembly 160.
1, 162, 163, 164 are trapped and released. 4-pole assembly 161
The individual DC offset potentials acting on the rods of section 166 may be used to trap ions in section 165 or section 16 into section 167 of quadrupole assembly 162.
5 to release ions. Mass vs. charge selection and resonant frequency excitation DC
Ion fracturing is configured in quadrupole assemblies 161,162,164. Ions are
Move between the forward facing quadrupole ion guide assembly and the reverse facing one by applying the appropriate DC offset potential to the individual sections of each multiple quadrupole ion guide assembly. The outlet section 168 and the two inlet sections 170, 171 comprise a four-pole assembly 162, 16
4 respectively. These additional sections, together with the 4-pole assembly 163,
Five steps are provided in an accelerated connection between the pole assemblies 162 and 164. High energy D
C accelerated CID ion fragmentation uses a long accelerating path provided by an additional quadrupole section,
Obtained especially at high background pressures. Multipaths are created through five set points to increase the ion internal energy leading to spallation.

The third quadrupole assembly 161 to the multi quadrupole assembly 160 in the hybrid TOF 170
Adds to the range of analytical functions performed compared to the hybrid TOF mass spectrometer shown in FIG. The hybrid TOF 170 is used to perform MS / MS ⁿ analysis functions that cannot use a hybrid TOF mass spectrometer, a triple quadrupole or a three-dimensional ion trap mass spectrometer as shown in FIG. New MS / MS ² with continuous ion beam and DC accelerated CID ion fragmentation for each MS / MS step
An example of the function sequence will be described below together with the hybrid TOF 170. Quadrupole assembly 161 operates with mass-to-charge selection, with or without repetitive ion trapping and release. 1. The quadrupole assembly 161 operates in mass-to-charge selection mode with or without repetitive ion trapping and release. 2. The host ion mass versus charge selected in quadrupole assembly 161 is accelerated into quadrupole assembly 162 with sufficient kinetic energy to cause DC accelerated CID spallation. 3. The quadrupole assembly 162 is operated in a mass-to-charge selection mode to select at least one first generation fragment ion with or without a repetitive ion trap and release mode. 4. The mass versus charge of the first generation fragment ions selected in quadrupole assembly 162 is
Acceleration through quadrupole assembly 163 and into quadrupole assembly 164 with sufficient kinetic energy results in DC accelerated CID ion spallation. The quadrupole assembly 164 is operated in a release mode with the RF-only ion trap to trap second generation debris ions. 5. Second generation debris ions are moved from quadrupole ion guide 164 into pulsed region 175 where they are pulsed into TOF floating region 176 and analyzed for mass versus charge.

A section 173 is added to the exit end 174 of the quadrupole ion guide assembly 164 to capture ions in the quadrupole ion guide 164 and to gate ions from the quadrupole 164 into the TOF pulsed region 1754. Serve as an alternative means of control. Ions are trapped in quadrupole assembly 164 by increasing the DC offset potential acting on the rods of section 173. Trapping at a DC offset potential acting on the pole of section 173, compared to using a DC restoration potential acting on lens 179,
It reduces any defocusing effects caused by the fringing field effect that occurs at the exit end 174. Section 173 operates primarily in an RF-only ion transfer mode to reduce or minimize the symmetric DC fringing field effect at the exit end 174 of quadrupole ion guide 164. Section 173 is associated with exit lens 179 or exit lens 179.
Instead, it is configured to operate for an ion trap or reverse ion acceleration function. As will be apparent to those skilled in the art, several unique analytical function sequences are possible in addition to the examples given above, with the four quadrupole ion guide assembly hybrid TOF 170 shown in FIG. The quadrupole assemblies 161, 162, 164 configured in the high background pressure region 171 operate independently in mass-to-charge selection mode and / or resonant frequency excited CID ion fragmentation mode. 4-pole assembly 16
1,162,163,164 work in conjunction with each other to obtain DC accelerated CID ion spallation. Extensive functionality is provided by the hybrid 4-pole T for a given analytical application
Performed to obtain MS / MS ⁿ mass spectroscopy using OF170.

An alternative embodiment to the AOI source hybrid 4-pole TOF 170 is shown in FIG. Referring to FIG. 5, multiple quadrupole assembly 180 configured within quadrupole TOF 194 includes individual quadrupole assemblies 181, 182, 183 spaced apart from electrostatic lenses 192 and 193. Electrostatic lens 192 is configured at the junction between quadrupole assemblies 181 and 182, and electrostatic lens 19 is configured at the junction between quadrupole assemblies 182 and 183. The electrostatic lens 192 replaces the quadrupole assembly 163 in the multiple quadrupole assembly 160 as shown in FIG. Electrostatic lenses 192 and 193 are connected to a DC power supply to allow trapping and release of ions from adjacent quadrupole assemblies. Ions are
It should be noted that although it is possible to move between the quadrupole assemblies in the forward and reverse directions within the multiple quadrupole assembly 180, the presence of the DC lens within the mutual quadrupole junction points to the additional end of the adjacent quadrupole assembly. The RF radial trapping field and the resonant AC field cause some distortion. This RF
The reduced propagation area of holes 195 and 196 in lenses 192 and 193, in addition to the AC field distortion, respectively, results in ion propagation losses between the quadrupole assemblies and reduces sensitivity. Performance is traded off against maintaining the ability to trap and release ions independently within the quadrupole ion guide assemblies 181, 182, 183 while significantly reducing costs from removing the RF power supply. I do. Alternatively, the electrostatic lens 19
The 2 and / or 193 are configured as multiple lens sets, allowing ions to traverse the junction between the quadrupole ion guide assemblies and thus electrostatically focus or accelerate them. The three individual sets of RF, +/- DC and resonant frequency waveform power supplies each apply potential to the poles of the quadrupole assemblies 181,182,183. The separated DC offset potential is applied to each section 184, 185, 18 of the multi-pole assembly 180.
6,187,188,189,190,191. 4-pole assembly 181,
182 and a portion of the 4-pole assembly 183 are configured in a higher background pressure vacuum process 197. Independent mass-to-charge selection and resonant frequency excited CID ion spallation are performed in quadrupole assemblies 181,182,183. DC accelerated CID ion crushing is 4
Obtained by ion acceleration between sections within the pole assembly or by ion acceleration between the quadrupole assemblies 181 and 182, 182 and 183 in the opposite direction. Alternatively, ions are accelerated in the opposite direction from the exit end of quadrupole assembly 183 into quadrupole assembly 183 to obtain DC accelerated CID ion spallation. Hybrid 4-pole T shown in FIGS. 1 and 4
As is apparent from the above description of the OF embodiment, the API source hybrid 4-pole TO
F194 operates at each MS / MS step to provide a range of MS / MS ⁿ mass spectrometry functions, with the option to use different methods to obtain mass versus charge selection and ion fragmentation. The hybrid 4-pole TOF194 has a triple quadrupole and a three-dimensional four-pole.
It can perform a mass spectrometry function that is used to perform polar ion trap mass spectrometry and cannot use either a triple quadrupole or a three-dimensional ion trap.

A less complex single or multiple quadrupole assembly can be configured with a hybrid quadrupole TOF device to reduce equipment costs and operational complexity. Flexibility in operation and analytical capabilities is reduced depending on the desired application, since the multiple quadrupole configuration is simple. The quadrupole ion guide assembly 61 of the multiple quadrupole assembly 8 includes a quadrupole ion guide 6
It acts to separate 0 and 62 both electrically and functionally. When the DC offset potential acting on pole 3 of quadrupole ion guide 61 increases to trap ions and decreases to pass ions from section 2 into quadrupole ion guide 61, the ions are converted to quadrupole assembly 60. Trapped and released in section 2 of FIG. 6 shows an electrospray ion source 212, four vacuum pumping steps 208, 209, 210, 211,
14 shows an alternative embodiment of a hybrid multipole ion guide TOF device 215 including a multiquad assembly 64 and a TOF mass spectrometer 216. The multiple ion guide 204 includes individual quadrupole assemblies 201, 202, 203 located along a common centerline 205 having individual RF, +/- DC and resonant waveform power supplies, each quadrupole set. Allows the implementation of independent mass selection and ion disruption functions as well as solids. In one aspect of the invention, all three RF power supplies operate at a common frequency and phase output. A common frequency and phase is set within each quadrupole assembly 201, 202,
Added to the 203 axially aligned rods to maximize ion transfer efficiency between the quadrupole assemblies. The quadrupole assembly 203 extends from the high background pressure vacuum pumping step 209 into a continuous low background pressure vacuum step 210. An example of a multi-quadrupole ion guide combination guided to mass-to-charge selection and fragmentation steps, together with the TOF mass spectrometry given above, is to a multi-quadrupole assembly 204 configured within a hybrid multi-quadrupole ion guide TOF device 215. Works.

Alternatively, the individual quadrupole assemblies 201 and 202 are configured as two sections of a quadrupole assembly where the RF potential acting on the poles of both sections starts from a common RF power supply. In this alternative embodiment, the multiple quadrupole assembly 204 includes two quadrupole assemblies, the first quadrupole assembly including sections 201 and 202, and the second quadrupole 203 includes a single section. Independent +/- DC (including offset DC) and resonance frequency waveforms are added to the quadrupole sections and bars of the assemblies 201, 202, 203 to implement independent mass-to-charge selection and ion fragmentation functions Is allowed in each quadrupole section or assembly. Compared to this alternative embodiment with a multiple quadrupole assembly 8 as shown in FIG.
The pole assembly 204 has been removed. The elimination of the segmented ion guide 8 of the quadrupole assembly 62 simplifies the operating sequence and reduces electronics costs. Many MS / MS ⁿ sequences described using the embodiment shown in FIG. 1 can operate with a dual quadrupole assembly 202 as shown in FIG. By setting an appropriate relative DC offset potential between the quadrupole sections and / or assemblies 201, 202, 203, DC accelerated CID ion spallation can be coupled between quadrupole sections or individual quadrupole assemblies. Through the points 206 and / or 207 in the opposite direction as before, or the quadrupole 203
It is generated by accelerating ions in the opposite direction from the exit end of. Vacuum second step 2
The background pressure in 09 is maintained above 0.1 mTorr to allow collisional attenuation of stable orbital ion energy and to allow CID ion spallation of ions within each multiple ion guide section or assembly. The local pressure at the entry end 203 of the segment or quadrupole 201 is higher due to free jet expansion and helps to increase the efficiency of ion guidance at the entrance of the multiple quadrupole assembly 204. Independent 4-pole assembly 61 or section 20
Elimination of the section within the junction between the two and four poles 203 reduces flexibility in simultaneously trapping ions of different ion populations in both the section 202 and the four pole 203. This reduced functionality simplifies the work and cost of the device by reducing variables and parts. Combining the inventive aspects shown in FIGS. 1-5, an alternative embodiment of the invention is configured into the hybrid TOF 215. For example, if the electrostatic lens is connected at the connection point 20
Included within 6 and 207 to allow trapping or movement of ions across junctions 206 and 207 within sections or quadrupoles. Electrostatics also help to isolate capacitive coupling of the electric field between the quadrupole assemblies. The multiple quadrupole assembly 204 also serves as a three-section ion guide with RF acting on all three section poles starting from one power supply. Several MS / MS ⁿ mass spectrometry functions are performed in this single RF delivery embodiment with reduced complexity and cost of electrical components.

The configuration of the quad assembly composed of the hybrid 4-pole TOF is MS / MS ⁿ It becomes even easier while maintaining the ability to perform analytical functions. Shows an alternative embodiment of the invention
In FIG. 7, the three sections of quadrupole ion guide 408 are hybrid APIT
OF mass spectrometry: configured in the meter. In the simplest embodiment, the RF potential is
Three divisions from common power supply RF with separate DC offset acting
Acts on bars 401, 402, 403. Individual +/- DC and resonance waveforms are classified as Category 4.
Added to the bars 01 and 402, the mass versus charge selection and the resonance frequency of the selected ion
Performs several-excitation CID crushing. Three section multipole ion guide 408 provides higher background pressure
A vacuum step 411 extends into the lower background pressure vacuum step 412. Section 402
, In RF only mode, or as described in US patent application Ser. No. 08 / 694,542.
MS / MS when combined with such TOF mass spectrometryⁿCombined with functional capabilities
Acting as a two-dimensional trap that is formed, ions are placed in the TOF pulsed region 415
Move to. The embodiment of FIG. 4 is not described in US patent application Ser. No. 08 / 694,542.
And two additional sections configured within the four pole assembly 408. Division 401 and 40
3 is the potential of the potential acting on section 408 during mass versus charge selection and ion fragmentation mode of operation.
It operates in a mode that helps to isolate or minimize fringing field effects. Edging
The minimization of the field effect is achieved by placing a quadrupole ion guide 408 at the entrance and exit ends 416 and 417.
It enables optimization of the trajectory of ions entering and exiting. For example, section 401 is dedicated to RF
Operate in mode for effective movement of ions from entry area 416 into section 408
I do. Kinetic energy and trajectory of ions entering multipole ion guide 408 at entry end 416
Is attenuated by collision with the background gas. The ions that cross section 401 are
The center line 41 where the effect of the defocusing of the DC border electric field on the propagation efficiency is minimal.
Enter section 408 near 8. The DC offset potential acting on the section 403 is
To trap ions in 402 or partition into TOF pulsed region 415
The ions from 402 are switched to gate. Pulsed region 415
Traversing ions are pulsed into the TOF floating region 414 and mass analyzed
. Replacement of a linear TOF flight tube shape with a TOF flight tube shape including an ion reflector shape
FIG. 7 shows an alternative embodiment.

The section 403 operating in the RF only mode has TOF pulsing from the multipole ion guide exit area 417 by shielding the non-uniform fringing field at the exit end of section 2 that occurs during different modes of operation of the section 402. A consistent ion trajectory is provided for ions traveling into region 415. Section 401 can also be operated in m / z selection and / or crush mode, and the parent or product ions can be forward or section 401
And 402 can be moved in the opposite direction. As a result, ions are divided into sections 401 and 402.
In between, it is spalled with DC ion acceleration to complete the resonance frequency CID function described in the previous example and US patent application Ser. No. 08 / 694,542. Ions traversing section 403 are accelerated back into section 402 and section 40 extends into vacuum step 411.
Within that portion of 2, a CID ion spallation results. The pulsing of the ions in the reverse direction from section 403 to section 402 synchronously switches the DC potential acting on the section 403 and the pole of the lens 419 to increase the energy of the ions in the exit region 417 before the ions are reversed. By accelerating along quadrupole centerline 418. DC electric field penetration from the poles of lens 419 and section 402 into section 403 is caused by the DC voltage difference acting between the two elements and assists ion acceleration into sections 403-402. The embodiment shown in FIG. 4 is cost effective thanks to a reduced number of multiple ion guide sections or individual quadrupole assemblies operating in a higher pressure vacuum region, with a certain compromise in functional flexibility. Enables full MS / MS ⁿ functionality in an efficient configuration.

An alternative embodiment of the three-dimensional multipole ion guide shown in FIG.
8 are configured to extend into the first vacuum pumping step 450. The ions created in the electrospray ion source 452 move through a capillary 453 into a first vacuum pumping step 450. Ions exiting the capillary 453 at the outlet end 454 enter the first multipole ion guide 441 where the ions act on the poles on the section 441 to act on the poles.
Radially limited by F field. Ions having m / z values that fall within the stability window determined by the electric field acting on the poles of section 441 pass through section 441 and move into section 442. MS / MS ⁿ with TOF mass vs. charge analysis
The function is obtained using a technique similar to that described for the three-section ion guide shown in FIG. An alternative to segmented ion guide 448 is to extend section 44 into vacuum step 450
2 inclusive. An additional multipole ion guide section is added to that portion of multipole ion guide 448 that extends into vacuum step 454. This configuration allows mass-to-charge selection and ion fragmentation functions at higher background pressures suitable for lower pressure operation for certain analytical applications. Multiplex 4 composed of hybrid 4-pole TOF mass spectrometer
Additional configurations of a pole or multi-section quadrupole assembly are shown in FIGS.

The independent quadrupole or segmented multipole ion guide assembly 502 shown in FIG.
F extends into the pulsing region 507. Ions traversing the length of the multipole ion guide 508 pass through separate quadrupole assemblies or sections 501, 502, 503, and
Move into pole or section 507. The relative DC voltage acting on the sections 503, 504 and the pole of the lens 506 traps ions in the quadrupole assembly 504. Division 50
The ions trapped within 4 block the RF voltage component and reduce the asymmetric DC potential of section 504, as described in US Pat. No. 5,763,878, which is hereby fully incorporated by reference. In addition to the poles, the ions are pulsed into the TOF floating region 510 by accelerating the ions radially through the gap between the two poles. "The 44th ASMS Conference on Mass Spectrometry and Ion Physics 1996"
Proceedings p. 795; James, C .; F describes replacement of trap lens 506 with quadrupole ion guidance with lateral ion extraction of ions trapped from quadrupole 504 into the TOF floating region.

The complete MS / MS ⁿ of the TOF mass vs. charge analysis equation is the hybrid T shown in FIG.
Obtained using the OF example. Individual 4-pole assemblies or sections 501, 502,
503 operates individually or in a supplementary manner to obtain mass-to-charge selection and / or ion CID disruption prior to TOF mass-to-charge analysis. Similar to the embodiment described above, multiple quadrupole assembly 508 provides different potentials to the rods of individual quadrupole assemblies 501, 502, 503, 504 with a common RF frequency and phase, RF, +
/ -DC and four independent sets of resonant frequency waveform power supplies. Each quadrupole assembly 501, 502, 503 located in the high-pressure vacuum process 512 operates independently and cooperatively in mass-to-charge selection and / or ion fragmentation mode to provide a T
Perform MS / MS step of MS / MS ⁿ mass spectrometry with OF mass vs charge analysis.
The quadrupole 507 is configured in a low-pressure vacuum region where little or no ion bombardment occurs with the neutral background gas. As a result, there is no collision attenuation occurring for ions trapped in quadrupole assembly 504 prior to lateral pulsing into TOF floating region 510.

The ions trapped in the quadrupole assembly 504 prior to lateral pulsing into the TOF floating region 510 traverse either axially along the length of the quadrupole assembly 504. I have. The axial trajectory of ions moving in the opposite direction of the quadrupole assembly 504 is
It is not possible to simultaneously command by operating the lens 511 to hit the TOF detector. To increase the number of ions having the required trajectory to strike the detector in the TOF tube, the ions may be laterally accelerated from quadrupole assembly 504 during the first pass of ions entering quadrupole ion guide 504, or Alternatively, ions need to be moved into quadrupole 504 with very low axial kinetic energy. As a disadvantage of the latter, the pulsed region filling time is very long, resulting in a reduced TOF pulse rate. Radial ion motion within the quadrupole assembly 504 due to the RF field without attenuation results in a lateral T
This causes spatial and energetic diffusion of ions accelerated into the OF floating region 510. An additional constraint to be considered when operating with a two-dimensional trap configured in the TOF pulsed region is that the multi-channel plate detectors commonly used in TOF analyzers typically have a It has a limited instantaneous charge drop linear dynamic range response on the order. If a very large number of ions, such as m / z, reach the detector within a 2 nanosecond time window, the detector output will reach saturation, resulting in signal amplitude distortion. The reduction in ion accumulation time in quadrupole 504 prior to pulsing of ions trapped in OF floating region 510 helps to avoid detector saturation. The potential acting to operate the lens set 511 is optimized to maximize the number of ions pulsed from the quadrupole 504 hitting the TOF detector.

FIG. 10 shows an alternative embodiment of a hybrid API source multipole ion guided TOF.
Referring to FIG. 10, an additional multipole ion guide 610 is configured between the segmented quadrupole ion guide assembly 608 and the TOF pulsed region 611. Multipole ion guide 610
Is surrounded by a septum 614 configured as a quadrupole ion guide or
When adding gas to the collision cell assembly 612 configured as a polar ion guide, it operates as a collision cell and operates in a mass-to-charge selection mode. Quadrupole ion guide 608
Segment including 601, 602 and 603, operated individually or collectively mass-to-charge selection and / or CID ion crushing mode, to obtain MS / MS ⁿ function with TOF mass to charge analyzed. Each section of the multipole ion guide 608 operates in a single pass or ion trap mode. In addition, the ions need to be mass-charged selected in the multipole ion guide 610 with DC acceleration or resonant frequency excited CID ion spallation. Multipole ion guide 608 is a continuous high background pressure vacuum process 61
From 3, the ions present from section 603 extend into a low pressure vacuum step 615 that is not scattered from collisions with neutral background gas molecules. The efficiency of ion transfer into the multipole ion guide 610 is aided by collision damping of the ions as they traverse section 601 and the portion of section 602 that is within vacuum pumping step 613. The configuration of the separate collision chamber assembly 612 including the multipole ion guide 610 allows for the introduction of collision or reactive background gases. The hybrid TOF embodiment shown in FIG. 1 is useful for investigating gas-phase ion neutral reactions or ion CID with full MS / MS ⁿ mass spectrometry capability.
Allows the use of different gases for crushing. Multipole ion guide 610 is TOF
It operates in single pass or ion trap and release mode, with gating of ions into the pulsed region 611. Additional RF multipole ion guidance is provided by the vacuum process 61
5, a multipole ion guide 610 configured in the collision chamber and the TOF pulsed region 61
1 to reduce the background pressure between the CID region 612 and a fourth vacuum step 618 maintained at a low background pressure. Multipole ion guide 608 is configured to extend into the poles of ion guide 610 to improve propagation efficiency, as described in US patent application Ser. No. 60 / 017,619, which is hereby incorporated by reference. The dual multipole ion guidance embodiment shown in FIG. 10 allows for a special mode of operation such as using two separate collision gases in an MS / MS or MS / MS ⁿ mass spectrometry sequence. The hybrid TOF embodiment as shown in FIG. 10 is a quadrupole ion guide assembly 608 constructed with different cross sections and having different +/− DC and RF frequency, phase and amplitude potentials acting on each quadrupole rod. Or 610 also allows for the performance of ion mass vs. charge selection and / or CID ion fragmentation functions. The ions are accelerated between the quadrupole assemblies 608 and 610 in forward and reverse directions, resulting in DC accelerated CID ion spallation.

FIG. 11 shows an alternative embodiment to a multipole ion guide hybrid TOF mass spectrometer operable in MS / MS ⁿ analysis mode. The segmented quadrupole ion guide assembly 708 is configured with sections 701, 702, 703 to provide a high background pressure vacuum process 710.
Located within. A second quadrupole ion guide assembly 704 located within the low background pressure vacuum process 711 is surrounded by a gas partition 713. Gas partition 713 adds collision gas into region 713 to increase the pressure in region 713 above the background pressure in vacuum step 711 when it is desired to operate ion guide 704 as a collision chamber. A third multipole ion guide 714 is located within the vacuum step 711 to effectively move ions from the multipole ion guide 704 into the pulsed 712 to provide sufficient vacuum pumping and high pressure collision area 713 and low pressure Enable during TOF pulsing region 712. The quadrupole ion guide 704 provides TOF in single pass or ion trap mode.
Operates with ion gating into the pulsed region 712. Placing the quadrupole ion guide assemblies 708 and 704 in a separate vacuum step allows for greater flexibility in the configuration of the multipole ion guide configuration, especially for the quadrupole assembly 708. Multipole ion guides that extend to one or more vacuum steps are configured with a relatively small inner diameter r ₀ to minimize neutral gas conductance from one vacuum step to the next. Minimizing gas conductance reduces the cost of vacuum pumping to a given background target pressure. Since the poles of the multipole ion guide assemblies 708, 704, and 714 start and end vacuum steps 710 and 711, respectively, no pumping constraints are imposed on any multipole ion guide configuration. The inner diameter r ₀ of the ion guides 708, 704, 714 is not restricted by the vacuum pumping conditions in the embodiment shown in FIG.

Similar to the previously described embodiment, maintaining the background pressure in the vacuum step 710 high enough,
As the ions traverse the length of the quadrupole assembly 708, it ensures that collisions occur between the background gas and the ions. The background pressure in the vacuum step 710 enables CID ion disruption of ions traversing the multipole ion guide 708 using resonant frequency excitation or internal section DC ion acceleration techniques. Each section in multipole ion guide 708 operates independently or in conjunction with other sections in m / z selection or CID ion fragmentation mode of operation. The voltage applied to the vacuum partition and the electrostatic lens 707 is divided into
It is set to pass from 03 to the multipole ion guide 704 or to trap ions within the multipole ion guide 708. Each section in the multipole ion guide 708 operates in a trapped or non-trapped mode by applying the appropriate relative DC offset potential to the poles of the adjacent section. Similar multipole ion guide 704 operates in a resonant frequency excited CID ion fragmentation mode with low or high background pressure in ion m / z selection mode or when the collision gas is in region 713. The ions are also DC accelerated into the multipole ion guide 704 with sufficient kinetic energy, resulting in CID spallation. The ions are accelerated forward or backward with sufficient kinetic energy between the quadrupole or multipole ion guide assemblies 708 and 704 to provide DC
This results in accelerated CID ion spallation. The combination of ion m / z selection and CID ion fragmentation functions is performed in quadrupole ion guide assemblies 708 and 704 to obtain various MS / MS ⁿ analysis functions along with TOF mass spectrometry. As an example of the collision chamber 612 shown in FIG. 10, a collision gas or a reaction gas is introduced into the region 713 with a component different from the component of the background gas in the vacuum process 710. The selected ion-molecule reaction is investigated by adding a suitable reaction gas into the collision chamber region 713. The reaction product ions are selected for mass versus charge, or are fragmented in one or more steps in either the quadrupole ion guide 704 or 708. The generated ion population that eventually flows through or is trapped by the multipole ion guide 704 is subsequently subjected to TOF mass spectrometry.

The embodiments of the invention shown in FIGS. 1-11 are some embodiments of the construction and operation of a hybrid multi-quadrupole ion guided TOF mass spectrometer, wherein ion mass versus charge selection and ion fragmentation This is done using at least one quadrupole ion located in the high pressure vacuum region. Multiple collisions between ions and neutral background gas molecules occur in a quadrupole ion guide configured in a high pressure vacuum region. The invention is not limited to the illustrated embodiments and the described techniques. For example, segmented quadrupole ion guides are described, where the individual quadrupole ion guides are located within a high background pressure range and independently or harmoniously with the m / z MS / MS Used to perform ⁿ analysis. The preferred embodiment is
The addition of the same RF frequency and phase from different synchronized RF power supplies to the individual quadrupole ion guides in the assembly. The RF amplitude, +/- DC (including DC offset) and resonance frequency waveforms vary independently for each quadrupole ion guide in such an assembly. Alternatively, RF works with different frequencies and phases, independently, on the individual quadrupole ion guides, including the assembly. One preferred embodiment having an asynchronous RF frequency and phase between quadrupole ion guides is the construction of an electrostatic lens within the junction between two adjacent quadrupole ion guides. Minimizing fringing field effects for ions traversing during guidance.

An example of the four-vacuum pumping step shown is m / z selection and / or CI
Reconfigured as a 2, 3 or 5 step vacuum system with D-fractionation, with at least one multipole ion guide located in the high background pressure vacuum region.
Different ion sources are configured with the hybrid multi-quadrupole ion guide TOF hybrid device. A uniform ion source operating at vacuum or partial vacuum is configured with a multipolar ion guide operating at high background vacuum pressure. A gas containing a multipole ion guide with an ion source operating in a vacuum is added to the vacuum region to operate in a high pressure m / z selection and ion fragmentation mode. The invention operates on variants of the TOF mass spectrometer configuration. For example, a TOF mass spectrometer is configured with a series pulsed region, multiple field ion reflectors or discrete dynode multipliers. In an alternative embodiment, a segmented multipole ion guide or a separate multipole ion guide portion located in the high pressure vacuum region is also configured to move ions, trap ions and any of the CIDs described above.
It operates in crush mode, as well as in m / z scan or m / z select mode, or a combination of these individual modes of operation. Example described the CID ions crushed in the invention, the ion mass-to-charge selection, and MS / MS ⁿ method is included in the alternative embodiment of the invention. In one such alternative embodiment of the invention, the last mass spectrometry step, either MS / MS or MS / MS ⁿ sequence, is performed by quadrupole ion guidance.

The detector 38 shown in FIG. 1 is used to detect ions prior to TOF mass spectrometry. One aspect of the invention is an arrangement of at least one, or a portion, one quadrupole ion guide configured and operative in a high pressure vacuum vacuum region in which multiple collisions between ions and neutral gas molecules occur. It is working. As noted above, an important feature of multiple ion guidance is that ions in a stable orbit are released simultaneously from one end of the ion guide or ion guide section operating in single pass or ion trap mode. Into the individual sections up to the opposite end of the multipole ion guide. Due to this feature, a segmented ion guide that receives a continuous ion beam is another multipole ion guide or other mass spectrometer that performs mass analysis on ions that are only partially released within the ion guide. Can be selectively released inside. In this way, ions provided in continuous ions are not lost during the discrete mass analysis step. Another aspect of the invention is that the multipole ion guide is configured with an additional quadrupole mass spectrometer or multipole ion guide collision chamber, or not, with a segmented multipole ion guide located in a high pressure vacuum region and the AOI source. Configuration. The segmented quadrupole ion guide is configured as a MS / MS or MS / MS ⁿ mass spectrometer with a segmented ion guide length section operating at a background vacuum pressure of 10 ^-4 Torr or higher. The electron multiplied ion detector configured with the quadrupole mass spectrometer of the invention is located and operates in a low or high background pressure vacuum region. Single or multi-pole vacuum process segmented multi-pole ion guides operating in a high pressure vacuum region, as a mass spectrometer or as part of a multi-pole mass spectrometer obtained in the configuration used to perform a wide range of MS / MS or MS / MS ⁿ analysis function for low cost and device complexity than. Operation of an API source quadrupole mass spectrometer at a high vacuum background pressure can reduce the size and cost of the device by reducing vacuum pumping speed requirements.

In the embodiment of the invention shown in FIG. 14, a multiple quadrupole assembly 1010 includes four independent quadrupole ion guide assemblies configured in an API quadrupole mass spectrometer. Quadrupole ion guide 1008 is configured with sections 1001 and 1002. Individual 4-pole assembly 1
003, 1004, and 1005 are configured with one section. Division 1001
And 1002 and quadrupole assemblies 1008, 1003, 1004, 1005 are insulated connection points 1018, 1019, 1 that separate each section or quadrupole assembly, respectively.
020 and 1021 are configured along a common center line 1011. Third vacuum step 1017, electrospray source 1012, segmented quadrupole ion guide 1008, quadrupole assemblies 1003, 1004 and vacuum pumping steps 1015, 1016, 101
Up to a connection point 1021 at 7 is configured and operates similar to the common elements of the hybrid 4-pole TOF embodiment as shown in FIG. The TOF mass spectrometer 40 of FIG. 1 is replaced by a four-pole assembly 1005 in the embodiment of the invention shown in FIG.

As shown in FIG. 2, the individual power supply units are respectively RF, +/− DC (
DC offset (including DC offset) and the resonance frequency waveform potential
Feed to 3,1004 bars. Independent RF and +/- DC power supply units also provide the potential to the poles of quadrupole assembly 1005. In the preferred embodiment of the invention, the same frequency and phase are added to all aligned rods in a multiple quadrupole assembly 1010 to move ions in a stable trajectory between the quadrupole assemblies in the forward or reverse direction. To maximize. Different RF amplitudes, +/- DC (including DC offset) and resonance frequency waveforms act on each individual 4-pole assembly rod. Different DC offset and resonance frequency waveforms affect different sections 1001 and 1002 of the ion guide assembly 1008. Alternatively, RF potentials having different frequencies and phases can be used during mass spectrometry operations.
Act on the individual 4-pole assemblies 1008, 1003, 1004, 1005. It is desirable to replace the quadrupole assembly 1003 with an electrostatic lens using asynchronous RF acting on the different quadrupoles and to include the electrostatic lens in the junction 1021 between the quadrupole assemblies 1004 and 1005. . Alternatively, the RF potential may be supplied from a common RF supply in section 100
Acting on 1,1002 rods and quadrupole ion guides 1003,1004.

A second vacuum step 1016 is performed when the ions traverse the length of the multi-quadrupole assembly 1010, the background pressure at which multiple collisions are limited to 10 ⁻⁴ Torr or more, which occurs between the ions and the neutral gas molecules. Works with The quadrupole ion guide assembly 1005 is maintained at a background pressure of less than 10 ^-4 Torr as the ions traverse the length of the quadrupole assembly 1005 with little collision between the ions and the background gas molecules. It is configured in a three vacuum process 1017. The quadrupole ion guide 1005 operates in mass-to-charge scanning or ion monitoring mode of choice. The embodiment shown in FIG. 10 shows all the MS and MS / MS analysis functions performed by the conventional triple quadrupole configuration as shown in FIG.
An S / MS analysis function can be performed. Four basic MS / MS triple quadrupole operating modes are shown in the preceding sections.

The MS / MS triple quadrupole mass spectrometry function shown above is performed in the API multiple quadrupole embodiment shown in FIG. 14 using the following operating sequence. 1. Section 1001 operates in ion single pass (non-trap) RF only mode with additional RF amplitude set to pass through the desired m / z value range. The relative DC offset potential acting on the poles of sections 1001 and 1002 is
It is set to move from section 1001 to section 1002 without DC accelerated ion crushing. 2. Section 1002 operates in an ion single pass (non-trapped) ion mass to charge selection mode. Ion mass versus charge selection is achieved by a quadrupole assembly 60 as shown in FIG.
This is done using section 1002 using the mass-to-charge selection technique described for section 2 of FIG. The RF amplitude is modulated while applying the appropriate +/- DC potential to the bar of section 1002. Alternatively, the RF modulation acts on the bar of section 1002 +/- D
Used with C and the resonance frequency waveform to perform single pass ion mass to charge selection. RF and +/- DC amplitude through the desired mass-to-charge range, with or without RF modulation, using the same mass-to-charge separation technique for MS / MS additions requiring mass-to-charge scanning for quadrupole 1008 Notch potential or resonance waveform m / z excitation frequency. 3. Quadrupole assemblies 1003 and 1004 operate in an RF only mode. The relative DC offset potential acting on the assembly 1002 and the quadrupole assembly 1003 can be selected with sufficient energy from the assembly 1002 through the quadrupoles 1003 and 1004 and into the quadrupole ion guide 1005 for mass-to-charge selection. The ions to be accelerated are set to accelerate and CID fragmentation of the accelerated ions occurs in quadrupole ion guides 1003 and 1004. After ion fragmentation has occurred, resulting in a low kinetic energy diffused ion beam traveling into the quadrupole ion guide 1005, a quadrupole 1 to attenuate the ion trajectory to the centerline.
The background pressure in the inlet end of 004 is maintained high enough. With sufficient ion kinetic energy collisional damping of the fragmentation, the kinetic energy of the ions entering the quadrupole 1005 is
It is determined by the relative DC offset potential acting on 04 and 1005. Slow ions traversing quadrupole 1005 are exposed to more RF cycles to improve mass-to-charge selection resolution. 4. Section 1005 operates in a mass-to-charge selection mode. When required in other MS / MS modes of operation, the range of mass-to-charge value selection is triple quadrupole MS / MS
Some are fixed in operation mode. The ion mass versus charge selection in the quadrupole assembly 1005 is made using the more conventional ramping of RF and +/- DC amplitude applied to the bars of section 1005. The m / z selective scanning ramps in sections 1002 and 1005 are synchronized to provide neutral loss scanning or monitoring of the selected fragmentation results. 5. Ion propagation from quadrupole ion guide 1005 via lens 1006 is accelerated to conversion dynode 1007. The generated secondary electrons and photons are detected by an electron or photomultiplier 1024. Alternatively, the ions are directly accelerated into electron multiplier 1024 and detected.

The embodiment of the invention shown in FIG. 14 is similar to the embodiment shown in FIG. 20, where the first and third analysis quadrupoles 554 and 556 each operate in a low pressure vacuum region to minimize ion collisions with the background gas. Additional analysis functions not possible with a conventional triode configuration can be performed. For example, a non-trapped continuous ion beam MS / MS ² analysis can be performed in section 100
1 operating in mass-to-charge mode and accelerating selected ions with sufficient energy into section 1002 to provide DC accelerated CID spallation in section 2 of quadrupole assembly 1008. Section 1001 operates in a stationary or scanning ion mass to charge selection mode. Alternatively, MS / MS ² analysis is performed with resonant frequency excited CID ion fragmentation of the host ions when it is not desirable to increase the internal energy of the fragmented ions. This is obtained in scanning or non-crushing mode as follows. 1. Section 1001 operates in a single pass (non-fractured) RF only mode, with additional RF amplitudes set to pass the desired range of m / z values. 2. Section 1002 operates in a single pass (uncrushed) m / z selection mode. Ion mass versus charge selection is performed with static single range ion m / z selection, or with iterative scanning over a range of ion mass versus charge values at the desired scan rate.
Simultaneously select multiple parent ion m / z values with mass-to-charge selection operation of resonant frequency excitation radiation. 3. The relative DC offset potential acting on the poles of the sections 1002 and the quadrupole ion guides 1003 and 1004 results in DC accelerated CID ion spallation of the selected ions of mass versus charge through the quadrupole 1003 and to the quadrupole 1004. Set to accelerate without. The quadrupole 1004 operates in a resonant frequency excited CID ion fragmentation mode to fragment host ions selected in the section 1002 m / z value ions. The first generation debris ions created in quadrupole 1004, with the appropriate relative DC offset potential set, allow quadrupole ion guide 1005 to pass ions with maximum m / z selectivity. Pass inside. 4-pole assembly 1004
Is maintained high enough to attenuate the ion trajectory after fracturing to obtain an ion beam that is radially attenuated to centerline 1011 with low energy spread. In this way, the kinetic energy of ions entering section 1005 is determined by the relative DC offset potential acting on the poles of quadrupole assemblies 1004 and 1005. 4. Quadrupole ion guide 1005 operates in a mass-to-charge selection mode. The selection range of ion mass vs. charge value may vary slightly from the triple quadrupole selection M when required for other applications.
Fixed within S / MS application. The ion mass versus charge selective scanning ramp of the four poles 1005 of the assembly 1002 is synchronized to be performed by a neutral loss scan or monitoring of the selected fragmentation results. 5. Ion propagation from quadrupole ion guide 1005 via continuation 1006 is accelerated into conversion dynode 1007. The generated secondary electrons and photons are detected by an electron or photomultiplier 1024. Alternatively, ions are accelerated or detected directly into electron multiplier 1024.

In the preferred embodiment at RF frequency and phase acting on all four quadrupole assemblies,
The ions effectively move with low kinetic energy from quadrupole ion guide 1004 to quadrupole 1005 to select a high resolution mass-to-charge scan within quadrupole 1005. The ions are temporarily charged with a quadrupole ion guide 1008, 100 so as to increase the ion residence time.
Trapped in 3,1004. Increasing the ion residence time increases the number of RF cycles for the ions, resulting in improved ion mass versus charge selection resolution or more effective resonant frequency excited CID ion spallation. The mass-to-charge selective scan speed can be adjusted to match the ion scan or release speed with, for example, a discrete m / z value scanning step, and the MS / M
Improve ^Sn performance. The electrostatic lens is the connection point 1 between the four pole assemblies 1004 and 1005
021. The electrostatic lens described above will cause any rapid changes in RF and +/- DC potentials acting on the poles of the 4-pole 1005 during mass versus charge selective scanning due to the effects of the potentials acting on the poles of the 4-pole assembly 1004. Help to separate. Additional electrostatic lenses also reduce any fringing field effects within junction point 1021, to different RF frequencies,
The phase and amplitude potentials are applied to the four poles 1004 and 1005. When using a detector operable at high background pressure, all multi-quadrupole ion guide assemblies 1008
Are configured in a single high background pressure vacuum process. The elimination of the vacuum pumping step reduces equipment cost, size and complexity while reducing little or no system flexibility or performance. The configuration of the multi-pole ion guide 1008 piecewise within a single vacuum pumping step minimizes neutral gas conductance during multiple vacuum pumping steps, except for any dimensional constraints on the inner diameter. Alternatively, the multiple quadrupole ion guide assembly 1008 may be configured to extend into the first vacuum process 1015 in a few vacuum process systems. A further alternative embodiment to a triple quadrupole analogous to a mass spectrometer composed of a multiple quadrupole ion guide assembly, with at least one quadrupole ion guide operating in mass-to-charge selection mode in a high pressure vacuum region, Figures 15-1
It is shown in FIG.

In an alternative embodiment of the invention, FIG. 15, in the dual quadrupole ion guide assembly 1110
Is configured with an additional quadrupole ion guide section 1104 configured in a low background pressure vacuum step 1117. The configuration of the quadrupole section 104 in the triple quadrupole mass spectrometer embodiment shown in FIG. 15 is a variation of the embodiment shown in FIG. In the embodiment of the invention shown in FIG. 15, the 4-pole 1104 is configured with a rod having a cross-section that is different from the cross-sectional dimension of the rod assembly of the multiple 4-pole assembly 1110. Multiple quadrupole assembly 1110 includes two sections 1108 and quadrupole assembly 1103. Sections 1101 and 1102 are:
It operates in mass-to-charge selection mode with CID fragmentation of ions in a quadrupole assembly 103 operating in RF only mode. Sections 1101, 1102 and quadrupole ion guide 11
The inlet end of 03 is configured in a high background pressure vacuum pumping step 1116. The electrostatic lens 1105 is configured within a connection point 1118 between the four poles 1103 and the four poles 1104. The lens 1103 has the effect of fringing field effects within the junction 1118 created by the different RF frequencies, phases and amplitudes and the difference +/− DC acting on the bar or adjacent 4-pole 1103 and 4-pole 1104 bars during operation. Minimize. The electrostatic lens also minimizes any coupling of RF or resonant waveform potential between the quadrupole assemblies 103 and 1104. Alternatively, the single electrostatic lens 1105 is configured as a plurality of electrostatic lenses to enable focusing or multi-step acceleration of ions traveling between the quadrupole assemblies 103 and 1104. Regardless of whether the multiple ion guide 1104 has a different geometric cross-section than the cross-sectional dimensions of the multiple quadrupole assembly 1108,
Quadrupole 1104 operates at a different RF frequency than that acting on quadrupole ion guide 1103. Triple quadrupole MS and MS / MS functional analysis are obtained in the embodiment of the invention shown in FIG. 15 using the techniques and methods described above.

In an alternative embodiment of the invention shown in FIG. 16, a multiple quadrupole ion guide 1208 is configured in a high vacuum pressure step 1210 and extends into a rod volume described by a separate multipole ion guide 1204. The quadrupole ion guide assembly 1203 includes the exit lens 1
Extending into 205, through which the ions effectively move into multipole ion guide 1204, even at low kinetic energies. Fully triple quadrupole MS and MS / MS functionality, with scanning and stationary ion m / z selection and CID fragmentation modes as described in the section above,
It is obtained by operating the assemblies 201, 1202 and the four poles 1203, 1204.

In an alternative embodiment of the invention shown in FIG. 17, an additional multipole ion guided collision chamber 13 is provided.
12 is added to a three vacuum pumping step multiplex quadrupole ion guide mass spectrometer.
Two or three section quadrupole guide assemblies 1308 are configured in a high vacuum pressure vacuum step 1314 that extends into a low vacuum pressure vacuum step 1315. The selected mass-to-charge and / or debris ions are transferred from the quadrupole ion guide 1309 to the gas septum 1313.
Into a quadrupole ion guide 1310 configured in a collision area 1312 surrounded by Multipole ion guide 1304 serves as the last mass spectrometer before ions are detected by detector 1305. Hybrid A shown in FIG. 10 or 11
Similar to the additional multipole ion guide shown in the PI quadrupole TOF hybrid embodiment,
The impinging or reacting gas is introduced into a region 1312 having a component different from the background gas component in the vacuum process 1314. A multipole ion guide 1310 located within a separate collision region 1312 increases experimental flexibility in MS / MS ⁿ analysis. The continuous beam MS / MS ³ provides mass to ion charge selection in section 1301, quadrupole ion guides 1309 and 1304, and D in section 1302 and multipole ion guide 1310.
Obtained in the embodiment shown in FIG. 17, operating with C-acceleration or CID ion spallation with resonant frequency excitation. When a dedicated MS function is required for a given amplitude analyzer operation, a similar embodiment of the invention is configured to reduce equipment cost, size and complexity.

In one embodiment of the invention, at least a portion of the segmented or non-segmented quadrupole ion guide consists of a high pressure vacuum process in which multiple collisions of ions with background neutral gas molecules occur. FIG. 18 shows a high pressure non-segmented quadrupole ion guide or continuous from a second vacuum pumping step 1401 that maintains the background pressure above 1 × 10 ⁻⁴ Torr into a third vacuum step 1402 where the detector 1403 is located. A mass spectrometer 1400 extending to FIG. The quadrupole ion guide assembly 1400 shown in FIG. 18 includes four parallel poles or bars evenly spaced around a common centerline 1402. In an ideal quadrupole mass spectrometer, each cross section has a hyperbolic shape, but generally round bars are used for ease of manufacture. FIG. 13 shows a cross section of four poles together with the round bars 104, 105, 106, and 107. The same RF and +/- DC potentials are applied to the opposing bars 104, 106 and 105, 107, respectively, for most quadrupole modes of operation. Adjacent bars are the same R
It has F and DC amplitudes, but their polarities are opposite. In addition, a common DC offset acts on all bars 104,105,106,106. Multi-frequency resonance waveforms act on the opposing bars as dipoles, or more complex resonance waveforms inductively or capacitively affect all four bars.

In the embodiment of the invention shown in FIG. 18, the non-segmented quadrupole ion guide 1400 begins with a second pumping step 1401 where the pressure is maintained high enough to traverse the length of the multipole ion guide 1400. Ions collide with neutral background gas molecules. The quadrupole ion guide 1400 may be coupled to RF and +/- with or without RF amplitude modulation as described above.
It operates to perform ion mass to charge selection by applying a DC or resonant frequency excited ion emission waveform. The ion mass versus charge selection scan can be performed by a conventional RF and +/- DC voltage amplitude scan or by applying the RF, +/- DC and resonance frequency waveform notch frequencies to the mass spectrometer over a suitable range. This can be done by attaching to ranges or by a combination of these methods. m
In the / z acceleration or m / z select mode of operation, the ions collide radially and axially below the background gas with the slowly selected ion m / z trajectory. Ions that have spent an increasing amount of time in quadrupole ion guide 1400 are exposed to an increased number of RF cycles. In this way, higher m / z select resolution is obtained for shorter multipole ion guide lengths than can be obtained using a quadrupole mass spectrometer with conventional methods operating at low background pressure. The operation of the multipolar ion guide in the analysis mode with a high pressure background gas in the APIMS analyzer shown in FIG. 18 allows for the construction of a smaller mass spectrometer system with reduced vacuum pumping speed requirements. Smaller quadrupole ion guide dimensions reduce the cost of driver-electronics, and higher pressure operation reduces the cost of vacuum equipment. Such systems improve APIMS system performance over devices that include quadrupole mass spectrometers operating at background pressures that are maintained to sufficiently avoid or minimize ion bombardment with neutral background gases. I do.

An Atmospheric Pressure Chemical Ionization (APCI) source 1405 is configured with and operates with a solvent supplied to the tip 1406 of the APCI nebulizer 1417 at a flow rate of less than 500 nl / min to greater than 2 ml / min. The APIMS embodiment shown in FIG. 18 is reconfigured with one of the following alternative sources, but with one API source of electrospray, inductively coupled plasma, glow discharge, multiple probe attachment, or one API source: It is not limited to combinations of different probes to be configured. The sample retentate is introduced into the APCI source 1405 with a pressure or positive displacement liquid supply. Liquid supply devices include, but are not limited to, liquid injectors with or without auto-injectors, separation devices such as liquid chromatography or capillary electrophoresis, syringe pumps, pressure vessels, gravity supply vessels or solution tanks. APCI source 1405
Operates by applying an electrical potential to the cylindrical electrode 1407 and the corona needle 1408, the endplate electrode 1409, and the capillary entrance electrode 1410. Counter-current drying gas 1411
Are passed through the heater 1412 and into the APCI source chamber 1405, and the end plate projection 141 is
It is directed to flow through the third hole 1414. The hole into the vacuum as shown in FIG. 18 is a dielectric capillary 1415 along with an inlet hole 1416. The potential of the ions flowing into the vacuum through the dielectric capillary 1415 is described in U.S. Pat.
3 is described. To create positive ions, a negative kilovolt potential is applied to the end plate electrode 1409 along with the attached electrode lug 1413 and the capillary inlet electrode 1410,
A positive kilovolt potential is applied to the cylindrical electrode 1407 and the corona needle 1408.
APCI sprayer 1417 and APCI heater 1418 remain at ground potential during operation. To create negative ions, the polarity of the electrodes described above is reversed. Alternatively, if a nozzle or conductive (metal) capillary is used as a hole into the vacuum, during operation,
A kilovolt potential is applied to the APCI corona needle 1408 and the cylindrical electrode 1407. The heated capillary is configured as a hole into the vacuum with or without countercurrent drying gas.

Unlike the ES source, the APCI source creates a sample and solvent molecular vapor prior to ionization. APCI ionization sources, unlike electrosprays, require a gas phase molecular ion charge exchange reaction. The sample liquid is supplied to the APCI probe 1 through the connection pipe 1420.
417 and APCI inlet probe tip 1406 with air atomization
Sprayed from. The atomized liquid droplet traverses cavity 1421 and has an APCI
Flow into vaporizer 1418. In the embodiment shown, cavity 1421 is configured with a drop sphere. Drop separator spheres 1424 remove large droplets from the spray created by the atomizer inlet probe and prevent them from entering vaporizer 1418. The drop sphere 1424 is removed when the flow rate of the introduced liquid is lower for better sensitivity. The liquid droplets are vaporized in a vaporizer 1418 to form a corona discharge region 1422 around and / or downstream of the corona discharge needle tip 1423.
Form steam prior to entry. An additional structure of the gas stream may be added, either independently or through an APCI inlet probe assembly, to assist in the transport of the liquid droplets and produce vapor through the APCI source assembly. The electric field is applied to the end plate 1409 and the capillary entrance electrode 14 together with the cylindrical lens 1407, the corona discharge needle 1408, and the projection 1413.
10 is formed in the APCI source 1405 by applying a potential. The applied gas potential, the opposite gas flow 1411 and the total gas flow through the vaporizer
422 is set to ensure a stable corona discharge around the corona needle tip 1423 and / or downstream thereof. Ions created in the corona discharge region 1422 by atmospheric pressure chemical ionization are repelled by the electric field toward the capillary hole 1416 against the countercurrent bath gas 1411. The ions migrate through the capillary bore 1416 into the vacuum and pass through the capillary 1415 into the first vacuum step 1425. If the capillary is configured with a heater 1426, with or without backflow gas, as a hole into the vacuum, additional energy will be transferred to the gas and ions within the capillary. This additional energy is beneficial for increasing additional drying or ion internal energy to promote ion fragmentation. A portion of the ions entering first vacuum step 1425 are directed through skimmer 1427 and to second vacuum step 1401.

Ions are created at or near atmospheric pressure from a sample retentate in an atmospheric pressure ion source 1405. The ions are supplied into the vacuum via a dielectric capillary 1415 through a vacuum septum 1428 supported by a neutral background gas. The neutral background gas creates a supersonic jet as it expands into the vacuum from outlet hole 1429 and accelerates ions entrained through multiple collisions during expansion. Part of the free jet expansion is via a skimmer 1427, which is part of the vacuum bulkhead 1431, and through a skimmer hole 1423.
Depending on the size of the pump and the pumping speed used in the second vacuum step 1401 via the pump port 1433, the background pressure can pass into the second vacuum step 1401 in the range of 10 ^-4 Torr to 10 ^-1 Torr. . A vacuum device that integrates one or more vacuum pumping steps is configured to move background neutral gas as the ions of interest traverse from the API source to the mass spectrometer inlet. The cost and size of the API / MS equipment is reduced when a minimum number of multiple vacuum pumping steps are configured and the pumping speed required for each step is minimized. Typically, three to four vacuum pumping steps are used for low cost and desktop API / MS equipment. The ions are passed through a vacuum ion barrier 1434 through a quadrupole ion guide 1400 to form a third vacuum pumping step 14400.
02. The vacuum step 1402 is evacuated through the pumping port 1435. Ions exiting the quadrupole ion guide 1400 pass through an exit lens 1436 that focuses the ions in the area between the lens 1437 and the detector 1403. The lens 1437 operates as a conversion dynode or as a repulsion plate to attract or repel ions into the detector 1403. Quadrupole ion guidance operates in a single pass or ion trap and release mode during ion mass versus charge scanning mode or single or multiple selection ion monitoring operation mode. The selected mass to charge value ion disruption operation is performed using the resonant frequency waveform excited CID method, as described above.

An alternative embodiment of the invention is shown in FIG. Sectioned or multiple quadrupole ion guide section 15
00 comprises a three-stage vacuum system with vacuum processes 1514, 1501, 1502. The three-section quadrupole ion guide assembly 1500 extends continuously from a high background pressure second vacuum pumping step 1501 to a background pressure vacuum step 1502.
MS or MS / MS function with appropriate, individual or shared RF, +/- DC or resonant frequency excitation waveform power supply to supply potential to section bar or independent four poles 1503, 1504, 1505 The range is made using a multiple quadrupole assembly 1500. A continuous ion beam MS / MS experiment is performed using the following operating conditions. 1. The quadrupole 1503 operates in a single value or scanning ion mass versus charge selection mode, depending on the analytical application, using the methods described above. 2. Four pole 1504 operates in RF only mode. The selected host ions of mass to charge are accelerated from quadrupole 1503 into quadrupole 1504. The appropriate relative DC offset potential is set so that the ions are accelerated across the junction 1507 at a sufficient
Attached to the poles 1503 and 1504 to produce accelerated CID ion spallation.
Alternatively or in combination, the resonance excitation frequency may be added to a four pole 1504 bar,
CID ion fragmentation of the host and / or fragment ions occurs within the quadrupole 1504. 3. Fragment ions travel across junction 1508 into quadrupole 1505 without fragmentation. 4. Quadrupole 1505 operates in a mass-to-charge selection mode that scans a single value of mass-to-charge. The ion mass versus charge selective scanning ramps of the four poles 1503 and 1505 are synchronized to perform a neutral loss scan or monitor the selected fragmentation results. 5. Ion propagation from quadrupole ion guide 1505 via lens 1517 is accelerated to conversion dynode 1518. The generated secondary electrons and photons are detected by the electron or photomultiplier 1519. Alternatively, the ions are accelerated directly into the electron multiplier 1519 and detected.

The electrostatic lens has a connection point 150 that insulates the quadrupole ion guides 1503 and 1504.
7 and at junction 1508 which insulates the quadrupole ion guides 1504 and 1505. The electrostatic lens has RF and + //
-Helps to isolate any rapid changes in DC potential. The added electrostatic isolation lens also reduces any fringing field effects on the ion traversing junctions 1507 and / or 1508 to allow different RF frequency, phase and amplitude potentials to be applied to the four quadrupole assembly 1500. It can be added to poles 1503, 1504, and 1505. FIG.
The triple quadrupole mass spectrometer shown in FIG. 9 has electrodes 1511 and 1512, a sample gas port 15
It is configured with a medium pressure glow discharge ion source including a pump 10 and a pumping port 1514. Some of the ions created in the glow discharge source pass through the skimmer 1513 and into the multiple quadrupole mass spectrometer assembly 1500. Alternatively, FIG.
The triple quadrupole 1500 shown in FIG. 1 is composed of an electric spray and an APCI atmospheric pressure ion source together with a glow discharge power supply vacuum process as a first vacuum process of three vacuum process devices.

The multiple quadrupole ion guide assembly 1500 is reconfigured with a single vacuum pumping step in an alternative embodiment of the invention as shown in FIG. Individual 4-pole assemblies 1715, 17
17, 1719 are configured along a common centerline in a high background pressure vacuum pumping step 1702. A triple quadrupole mass spectrometer as shown in FIG. 21 has a vacuum process 17 evacuated by vacuum pumping ports 1711, 1712, 1713, respectively.
01, 1702, 1703 and three vacuum pumping process systems. Exit lens 1 configured as a component of vacuum bulkhead 1705 but electrically insulated
704 minimizes neutral gas conductance into the third vacuum step 1703 where the conversion dynode and the electron multiplying detector 1706 are configured. This allows the maintenance of a low background pressure vacuum within the vacuum process 1703 with a smaller, reduced vacuum pumping speed and a lower cost pump. Ions entering triple quadrupole assembly 1700 through holes in skimmer 1709 that are electrically insulated from vacuum septum 1710
Undertake MS or MS / MS analysis using the operating method as described above for the triple quadrupole assembly 1500 shown in FIG. Alternatively, as described above for the triple quadrupole assembly 1500, an electrostatic lens is configured in the junctions 1716 and 1718 to insulate the quadrupoles 1715 and 1719 from the quadrupole 1717. DC voltage is at connection point 1
Switch to the additional electrostatic lens configured in 716 and 1718 to allow independent trapping and release of ions from quadrupoles 1715, 1717, 1719 for individual analysis applications. The multiple resonance frequency emission and the excitation waveform have four poles 1715,
Added to the rods 1717 and / or 1719, as noted in the previous section,
A quasi-MS / MS ⁿ mass spectrometry is achieved. For example, to perform quasi-MS / MS ³ mass spectrometry, MS / MS with host ion mass-to-charge selection performed in 4-pole 1715
A first mass spectrum is obtained using an operating mode. Maternal ions are disrupted using a single mass range resonant frequency excited CID ion disruption operation or DC accelerated CID ion disruption or a combination of both in quadrupole 1717, and a mass-to-charge scan is performed at quadrupole 1719. The second mass spectrum is obtained by two mass range resonance frequency excited CID fragmentation performed in a quadrupole 1717, where the second generation ions are created by performing the CID fragmentation of the host and first generation ions simultaneously. .
Alternatively, single mass range resonant frequency excited CID ion fragmentation of first generation fragment ions combined with DC accelerated CID fragmentation of the host ion is performed in quadrupole 1717, while the second mass spectrum is of quadrupole 1719. Obtained by scanning. The first acquired mass spectrum is then extracted from the second acquired mass spectrum to obtain a quasi-MS / MS ³ mass spectrum of the second generation debris ions.

The APIMS analyzer cost and complexity is further reduced by configuring the ion detector in a high pressure vacuum process according to the present invention. A multi-channel plate detector that can operate at pressures greater than 1 × 10 ⁻⁴ Torr is available due to the configuration of the plate including channels of small diameter and short length. In the multi-channel plate detector, the cascade selection process resulting from the impact in the detector channel is shorter than the background pressure mean free process, minimizing electron scattering and signal loss. The single section quadrupole ion guide 1800 is shown in FIG.
As shown in the figure, the invention is constituted by an electrospray mass spectrometer of two vacuum pumping steps constituted according to the invention. The first vacuum step 1801 is typically evacuated through a pumping port 1811 returned by a rotary pump. Second vacuum process 1
801 is evacuated through a pumping port 1812 returned by a small turbo-molecular pump or rotary vacuum pump. Quadrupole ion guide 1800 with exit lens 1804 and multi-channel plate detector 1806 is configured in high pressure vacuum process 1802. Ions passing through the holes in the skimmer 1809 are subjected to a four-pole 1800, as described above, using an ion mass-to-charge selection operation to monitor a single value or selected ions or a mass-to-charge selection operation to scan. Mass vs. charge analysis. FIG.
The embodiment of the invention as shown in Fig. 1 is configured as a small and low-cost device while maintaining the full MS analysis capability. MS / MS and equivalent quasi-MS / MS ⁿ mass spectrometry functions are performed using the triple quadrupole embodiment of the invention as shown in FIG.

The individual quadrupole assemblies 1913, 1915, 1917 are in a high background pressure vacuum process 1
902 are configured along a common centerline. An electrospray MS analyzer as shown in FIG. 23 is configured with two vacuum pumping steps 1901 and 1902 evacuated through vacuum ports 1911 and 1912, respectively. The triple quadrupole ion guide assembly 1900, exit lens 1904, and multi-channel plate detector 1806 are configured in a second vacuum pumping step 1902. MS / MS and quasi-MS / M using the description method for multiple quadrupole ion guides configured as shown in FIGS.
The range of the ^Sn mass spectrometry function is performed using the embodiment of the invention as shown in FIG. The individual quadrupole assemblies 1913, 1915, 1917 are in single pass or ion trap and open mode, with adjacent quadrupoles, skimmer 1909 and exit lens 1904.
It operates by matching the DC offset potential acting on the DC offset. Alternatively, the electrostatic lens may include a junction 1914,1 between the four poles 1913,1915 and four poles 1915,1917.
917, each of which is capable of independent ion trapping and release operations of individual 4
Allowed within poles 1913, 1915 and 1917. The configuration of the electrostatic lens in the junctions 1914, 1917 has different R acting on each quadrupole during MS and MS / MS functions.
It also allows operation of all three four poles with F frequency, phase and amplitude. FIG.
Embodiments of the invention as shown in FIG. 3 allow for the construction of a small, low cost API source triple quadrupole mass spectrometer. MS, MS / MS and quasi-MS / MS ⁿ mass spectrometry operation ranges are performed using the API source triple quadrupole mass spectrometer described above constructed according to the invention.

Although the present invention has been described in terms of particular preferred embodiments, it will be apparent and understood by those skilled in the art that various modifications and substitutions are within the scope of the invention as defined in the appended claims. You. In particular, other types of mass spectrometers, including but not limited to conventional quadrupole, magnetic sectors, Fourier transform three-dimensional ion traps, and time-of-flight mass spectrometers, comprise embodiments of the invention as described herein. You. Any of the ion sources, including but not limited to the atmospheric pressure ion sources described herein, and the ion sources that create ions in a vacuum described above are compatible with the embodiments of the invention described herein. Further, various references relevant to the disclosure of the present application are cited above and are incorporated by reference.

[Brief description of the drawings]

FIG. 1 is a diagram of an electrospray ion source orthogonal pulsed time of flight mass spectrometer with an ion reflector configured with three independent multipole ion guides located in series along a common axis. A third multipole ion guide extends continuously from the second vacuum step to a third vacuum step.

FIG. 2 is a block diagram of a voltage supply unit and a control module for three multipolar ion guide assemblies and surrounding electrodes shown in FIG. 1;

FIG. 3 is a diagram of potentials acting on the quadrupole element shown in FIG. 1 during MS / MS analysis.

FIG. 4 is an alternative embodiment of an atmospheric pressure ion source hybrid TOF mass spectrometer configured with quadrature pulse generation in a TOF mass spectrometer and configured with three quadrupole ion guide assemblies.

FIG. 5 is an alternate embodiment of an atmospheric pressure ion source hybrid TOF mass spectrometer configured with an electrostatic lens located within the junction between adjacent multipole ion guides.

FIG. 6 is a diagram of an electrospray ion source orthogonal pulsed time of flight mass spectrometer having an ion reflector flight tube configuration configured with three multipole ion guides.

FIG. 7 is a diagram of an electrospray ion source orthogonal pulsed time-of-flight mass spectrometer having a straight flight tube configuration configured with a three-section multipole ion guide, one section extending to two vacuum pumping steps in succession. It is.

FIG. 8 is a diagram of an electrospray ion source quadrature pulsed time of flight mass spectrometer configured with three quadrupole ion guide assemblies, wherein the multiple quadrupole assembly extends to three vacuum pumping steps.

FIG. 9 shows that the second extends from the second vacuum step to the third vacuum step, and the third is a TOF
FIG. 3 is a diagram of an APITOF orthogonal pulse mass spectrometer configured with three quadrupole ion guide assemblies, the orthogonal pulse region of the mass spectrometer.

FIG. 10 is first configured as a three-section multipole ion guide extending to second and third vacuum pumping steps, and second thereof configured as an ion collision chamber in a third vacuum step. FIG. 4 is an alternative embodiment of an orthogonal pulsed API source TOF mass spectrometer configured with two multipole ion guide assemblies.

FIG. 11: APITOF quadrature pulsed mass configured with a three-section quadrupole ion guide assembly located in a second vacuum process and second and third multipole ion guide assemblies located in a third vacuum process. It is a figure of an analyzer.

FIG. 12 is a diagram of a portion of a stability diagram to quadrupole ion guidance.

FIG. 13 is a cross-sectional view of a quadrupole ion guide configured with a round bar.

FIG. 14 is a diagram of an electrospray ion source quadrupole mass spectrometer configured with three quadrupole ion guides having a second quadrupole ion guide extending continuously from a second to a third vacuum pumping step. .

FIG. 15 is a diagram of an electrospray source quadrupole mass spectrometer configured with three quadrupole ion guides. The third quadrupole ion guide is located in a low pressure third vacuum step with an electrostatic lens configured in the junction between adjacent second and third quadrupole assemblies.

FIG. 16 shows an electrical configuration with two quadrupole ion guide assemblies located in a high pressure second vacuum pumping step, with its outlet end extending to a second ion guide located in a low pressure third vacuum step. FIG. 3 is a diagram of a spray source quadrupole mass spectrometer.

FIG. 17 on an assembly section extending continuously from the second to the third vacuum pumping step and configured with detectors located in the second and third multipole ion guides and the third vacuum step; FIG. 4 is an illustration of an electrospray source multiple quadrupole mass spectrometer configured with a dual quadrupole assembly having a second quadrupole.

FIG. 18 is a diagram of an atmospheric pressure chemical ionization source single quadrupole mass spectrometer configured with a quadrupole ion guide extending continuously from a second to a third vacuum pumping step.

FIG. 19 is an illustration of a glow discharge ion source triode mass spectrometer configured with a third quadrupole ion guide extending continuously from a second to a third vacuum pumping step.

FIG. 20 is an illustration of an electrospray ion source connected to a conventional triple quadrupole mass spectrometer.

FIG. 21 is a diagram of a triple quadrupole mass spectrometer, wherein all three quadrupole ion guide assemblies are in a second vacuum step at high background pressure and in a third vacuum step at low background pressure. It is configured with the configured detector.

FIG. 22 is a diagram of an electrospray ionization source connected to a single quadrupole ion guide mass spectrometer, wherein the quadrupole ion guide and ion detector are configured in a high background pressure vacuum process. You.

FIG. 23 is a diagram of an electrospray ionization source connected to a triple quadrupole mass spectrometer, wherein the triple quadrupole ion guide mass spectrometer and ion detector are configured in a high background pressure vacuum process. Is done.

──────────────────────────────────────────────────続 き Continuation of front page (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE ), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY , CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IS, JP, KE , KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW (72) Inventor Andrien, Plus, A. Junior. 06405 Branford, Connecticut, United States, Business Park Drive 29, Analytica of Branford, Incorporated (72) Inventor Garsik Erol E. 06405 Branford, Connecticut, United States, Business Park Drive 29, Analytica of Branford, Inc. F-term (reference) 5C038 FF04 JJ06

Claims (24)

[Claims] 1. An analyzer for a chemical species comprising: (a) an ion source for operating at substantially atmospheric pressure to produce ions from a sample material; and (b) a vacuum device with at least one vacuum pumping step. (C) a detector configured in at least one of the vacuum pumping steps; and (d) a configuration of at least two multipolar ion guides in the at least one vacuum pumping step; At least a portion of the ion guide is located in at least one of the vacuum pumping steps, and the background pressure in the vacuum step is caused by collisions between the ions and neutral gas molecules in the two multipole ion guides. And (e) means for selecting mass to charge in at least one of said multipolar ion guides. 2. The apparatus according to claim 1, wherein said ion source is an electrospray ion source. 3. The ion source of claim 2, wherein said ion source is an atmospheric pressure chemical ionization ion source.
The device according to 1. 4. The apparatus according to claim 1, wherein said ion source is an inductively coupled plasma ion source. 5. The apparatus according to claim 1, wherein said ion source is a glow discharge ion source. 6. The apparatus of claim 1 wherein said multipole ion guide is quadrupolar. 7. The apparatus of claim 1, wherein said multipole ion guide is six poles. 8. The apparatus of claim 1, wherein said multipole ion guide is eight poles. 9. The apparatus of claim 1, wherein said multipole ion guide has more than eight poles. 10. An analyzer of a species comprising: (a) an ion source for operating at substantially atmospheric pressure to produce ions from a sample material; and (b) a vacuum device with at least one vacuum pumping step. (C) a detector configured in at least one of the vacuum pumping steps; (d) a mass spectrometer for performing mass-to-charge analysis; and (e) at least one of the vacuum pumping steps in the vacuum pumping step. At least a portion of each of said at least two multipole ion guides is located in at least one of said vacuum pumping steps, wherein said background pressure in said vacuum step, impinging said Maintaining high enough between ions and neutral gas molecules to occur with the ions in the two multipole ion guides; and (f) at least one of the multipole ion guides. Means for selecting mass-to-charge in the ion guide; and (g) performing mass-to-charge analysis in the mass spectrometer. 11. The apparatus according to claim 10, wherein said at least two multipole ion guides are configured in succession along a common centerline, and said ions move from one multipole ion guide to the next. 12. The mass spectrometer according to claim 10, wherein said mass spectrometer is a quadrupole mass spectrometer.
The described device. 13. The apparatus according to claim 10, wherein said mass spectrometer is a quadrupole mass spectrometer. 14. The apparatus of claim 10, wherein said at least two multipole ion guides are configured with said mass spectrometer to form a triple quadrupole mass spectrometer. 15. The apparatus according to claim 10, wherein said mass spectrometer is a magnetic sector mass spectrometer. 16. The apparatus according to claim 10, wherein said mass spectrometer is a Fourier transform mass spectrometer. 17. The apparatus according to claim 10, wherein said mass spectrometer is an ion trap mass spectrometer. 18. The apparatus according to claim 10, wherein said mass spectrometer is a time-of-flight mass spectrometer. 19. The apparatus according to claim 10, wherein said mass spectrometer is a quadrature pulse time-of-flight mass spectrometer. 20. The apparatus according to claim 10, wherein said mass spectrometer is a linear pulse time-of-flight mass spectrometer. 21. The apparatus according to claim 10, wherein said mass spectrometer is a time-of-flight mass spectrometer including an ion reflector. 22. A chemical species analyzer, comprising: (a) an ion source for operating at substantially atmospheric pressure to produce ions from a sample material; and (b) a vacuum device with at least one vacuum pumping step. (C) a detector configured in at least one of the vacuum pumping steps; and (d) a configuration of the at least two multipolar ion guides in at least one of the vacuum pumping steps, At least a portion of the polar ion guide is located in at least one of the vacuum pumping steps, and the background pressure in the vacuum step increases the collision between the ions and neutral gas molecules in the two multipolar ion guides. (E) means for maintaining mass high enough to occur with ions, and (e) means for selecting mass-to-charge within the at least one multipole ion guide; Means for disrupting collision-induced dissociated ions in one of said multipole ion guides. 23. An analyzer of a chemical species comprising: (a) an ion source for operating at substantially atmospheric pressure to produce ions from a sample material; and (b) a vacuum device with at least one vacuum pumping step. (C) a detector configured in at least one of the vacuum pumping steps; (d) a mass spectrometer for performing mass-to-charge analysis; and (e) at least one of the vacuum pumping steps in the vacuum pumping step. At least a portion of each of said at least two multipole ion guides is located in at least one of said vacuum pumping steps, wherein said background pressure in said vacuum step, impinging said Maintaining high enough between ions and neutral gas molecules to occur with the ions in the two multipole ion guides; and (f) at least one of the multipole ion guides. Means for transferring mass to charge in the ion guide; (g) means for breaking up collision-inducing separated ions in at least one of said multipolar ion guides; and (h) mass in the mass spectrometer. An apparatus comprising performing a charge analysis. 24. An ion source, a vacuum device with at least one vacuum pumping step, a mass spectrometer, and at least two configured in adjacent alignment along a common centerline in at least one said vacuum step. A method for analyzing a chemical species utilizing two multipole ion guides and a detector, the method comprising: (a) creating ions in the ion source; and (b) combining the ions with the at least one multiplicity of ions. Feeding into the polar ion guide;
(C) activating at least a portion of said at least two multipole ion guides at a background pressure in at least one said vacuum step, wherein collisions of said ions with respect to said ions traverse said at least one multipole ion guide. (D) selecting the mass-to-charge of the ions in at least one of the multipole ion guides; and (e) collisionally inducing at least one of the multipoles. Separating the ion guide; (f) moving the ions from the first multipole ion guide into the second multipole ion guide; and (g) ions resulting from the selection of mass to charge. A method comprising mass spectrometry of a population and performing said ion breaking step performed in said first and second multipole ion guides.