WO2022028329A1

WO2022028329A1 - Sample injection mechanical arm assembly and high-flux automatic sample injection system and method

Info

Publication number: WO2022028329A1
Application number: PCT/CN2021/109684
Authority: WO
Inventors: 朱建雄; 朱光皓
Original assignee: 广东联捷生物科技有限公司
Priority date: 2020-08-04
Filing date: 2021-07-30
Publication date: 2022-02-10
Also published as: CN112083180A; CN213715247U; CN213715248U; CN213715246U

Abstract

A sample injection mechanical arm assembly, a novel high-flux automatic sample injection system, and a high-flux automatic sample injection method. The sample injection mechanical arm assembly comprises mechanical arms (4, 5) and a first spline shaft (31); the mechanical arms (4, 5) comprise a vertical shaft and horizontal moving arms (46, 54); one end of each of the horizontal moving arms (46, 54) is vertically connected to the vertical shaft; the horizontal moving arms (46, 54) can rotate around the vertical shaft; the other end of each of the horizontal moving arms (46, 54) is provided with a sample injection needle mounting needle seat (47, 55); and the rotation of the vertical shaft is driven by driving a worm gear (427, 514) by means of the first spline shaft (31). The high-flux automatic sample injection system comprises the sample injection mechanical arm assembly, a sample circulation bin for automatically conveying a sample to be tested, and a control module. The mechanical arm assembly provided by the present invention is simple in structure and capable of rapidly completing sampling and sample injection. According to a high-flux automatic sample injector and the sample injection method, all sampling and sample injection operations can be automatically completed, and the sample injection speed is high.

Description

Sampling robot arm assembly and high-throughput automatic sampling system and method

technical field

The invention belongs to the technical field of analytical instruments, and in particular relates to a sample-introduction mechanical arm assembly, a novel high-throughput automatic sample-injection system, and a high-throughput automatic sample-injection method.

Background technique

Modern analytical instruments are generally equipped with automatic samplers, which make the analysis process completely automated, which not only saves manpower, but also improves the throughput (sample analysis speed) of the analytical instrument, and avoids human errors.

There are many types of autosamplers on the market, but the basic structure usually includes a robotic arm, a sample storage device such as a sample tray, a needle pump, and a switching valve (injection valve). The sample storage device is often equipped with a thermostat to lower and maintain the sample temperature at around 4°C, thereby avoiding or slowing down the decomposition of the sample due to heat. During operation, the robotic arm and the needle pump cooperate to transport the samples in the sample storage device to the detector one by one for measurement. After each injection, the delivery pipeline is cleaned to eliminate residues and contamination. If the detection system involves high pressure, such as high performance liquid chromatography, the sample is first delivered to the injection valve, and then the sample is introduced into the high pressure path for measurement by switching the injection valve.

At present, almost all autosamplers used in analytical chemistry typically take between 1 and 2 minutes to inject a sample. For most valuable detection instruments, such as chromatographs, nuclear magnetic resonance instruments, LC/MS/GC instruments, etc., the analysis time is long, and the sample injection speed is a little slower. For less expensive instruments, such as various spectrometers, electrochemical detectors, thermal analyzers, etc., the analysis speed only takes a few seconds, and it is not worth the expense to increase the sample injection speed, because the autosampler is often more expensive than the instrument itself It is more economical to purchase more instruments if there are more samples.

However, for expensive instruments with fast analysis speed, such as flow injection mass spectrometers, the configuration of the current common autosampler will generate a lot of waste. The analysis time of injection is at most about half a minute, and the time required for sample suction, positioning, and cleaning of the automatic sampler is at least half a minute, which reduces the value of the instrument by more than half. In such a situation, a high-throughput (high-speed) autosampler is highly desirable.

The most used high-throughput autosamplers in the world are the CTC series and Triplus series autosamplers from CTC Company in Switzerland. However, the mechanical movement speed of the CTC sampler is not significantly faster than other similar products. They are the most popular analytical sampler only because of the large capacity of the CTC sample storage device, 6 to 30 sample trays, each sample tray can hold 54 to 96 samples, a CTC sampler can hold 300 to 2800 If the analysis time of each sample is about 1 minute, it is possible to configure a CTC autosampler that can hold 2400 samples to keep the instrument running automatically all day long. However, for most detectors, including mass spectrometers, the data acquisition time is only a few seconds. If the flow injection method is used to directly use the detector for analysis and detection, the time required to analyze a sample is mainly spent in injecting the sample. In the process, for high-end and expensive detectors with fast data collection speed, the resulting waste is very large, and the efficiency of the instrument will be less than 10% in most cases.

The analog internal standard technology is an analysis technology that eliminates signal drift by injecting the sample to be tested and the standard sample successively. It is mainly suitable for quantitative analysis of liquid phase mass spectrometry. for quantitative analysis. The mass spectral signal integration time for each sample analysis only takes 1 to 5 seconds, and the total injection of samples and standards is 5 to 10 seconds. Each mass spectrometer can complete the analysis and detection of up to 17,280 samples within 24 hours. Using the existing autosampler, a maximum of 1,440 samples can be injected in 24 hours, which is only 8% of the highest throughput that can be achieved by the simulated internal standard flow injection method, and 92% of the throughput of the mass spectrometer is wasted. A high-end quantitative analysis mass spectrometer is worth about RMB3 million. Fully exploiting the throughput of its direct analysis can reduce the cost of sample analysis by more than 90%, so that the cost of high-end analysis is basically the same or even lower than that of low-end analysis. However, to achieve this goal, the existing autosamplers on the market are far from meeting the requirements. Not only are they too slow, but the capacity of the sample storage device is far from enough.

In addition, the existing high-throughput sample injectors for analytical chemistry have three biggest defects: (1) the movement speed of the robotic arm is not fast enough, and it generally takes 1-2 minutes to complete a sample injection; (2) the sample storage device has a small capacity , most of them can only store hundreds of samples; (3) the volume is large, in order to store more samples, most of the existing automatic samplers put the sample tray on a large plane, so that the automatic sampler occupies The space is large, the range of displacement of the robotic arm is also large, and it takes longer to complete a sample injection process. The CTC autosampler adopts a box-type sample storage device, but the robotic arm is used to open and close the box, which not only greatly slows down the sampling speed, but also increases the length of the robotic arm and the stability of its operation.

Therefore, for flow injection analysis, especially flow injection mass spectrometry quantitative analysis, it is necessary to develop a true high-throughput autosampler.

SUMMARY OF THE INVENTION

The purpose of the embodiments of the present invention is to provide a sample injection robotic arm assembly, a high-throughput automatic sampling system including the robotic arm assembly, and a high-throughput automatic sampling method, aiming to solve the problem of sampling in the prior art. slow problem.

A first embodiment of the present invention provides a sample injection robotic arm assembly, including a robotic arm and a first spline shaft, the robotic arm includes a vertical axis and a horizontal moving arm, one end of the horizontal moving arm is perpendicular to the vertical axis and Fixed or detachable connection, and the horizontal moving arm can rotate around the vertical axis, the other end of the horizontal moving arm is provided with a needle mounting needle seat, and the rotation of the vertical axis passes through the first spline The shaft drives the worm gear to drive.

Further, the rotation of the first spline shaft is driven by a first drive motor, and the first drive motor is disposed at the end of the first spline shaft.

Further, the robotic arm is made of lightweight materials such as aluminum alloy, titanium alloy or carbon fiber, etc. or a combination thereof.

Further, the sample introduction robotic arm assembly also includes a slide rail, a second spline shaft, a horizontal conveyor belt and a vertical conveyor belt. The robotic arm is sleeved on the slide rail, and the horizontal conveyor belt controls the horizontal movement of the robotic arm. The conveyor belt is sleeved on the second spline shaft and controls the up and down movement of the mechanical arm. The second spline shaft is driven by a second drive motor, and the second drive motor is arranged at the end of the second spline shaft. The horizontal The conveyor belt is driven by a third drive motor, which is provided at the end of the slide rail.

Further, in the slide rail, the first spline shaft and the second spline shaft are arranged parallel to each other.

Further, the sample injection robotic arm assembly includes two robotic arms, the structures of the two robotic arms are the same or different, one is used for injecting a standard sample, and the other is used for injecting a sample to be tested.

Another embodiment of the present invention provides a sample introduction robot arm assembly, including a robot arm for installing and removing an injection needle, and a horizontal conveyor belt separated from the robot arm, the horizontal conveyor belt spans the standard sample injection area and the sample to be tested A sample injection area, and a needle seat of a sample injection needle is respectively installed on the two equalization points, and the mechanical arm is used for installing the sample needle on the needle seat and removing the sample needle from the needle seat.

Another object of the embodiments of the present invention is to provide a high-throughput automatic sampling system, the sampling system includes a sampling robotic arm assembly, the sampling robotic arm assembly is XYZ trilinear, or XYR, XRZ, RYZ two Linear plus one rotary axis, or XRR, RYR, RRZ one linear plus two rotary axes, or combined robotic arm assembly with three RRR rotary axes, the injection needle installed on the needle seat of the robotic arm, the standard compartment for placing standard samples, And a sample circulation bin and a control module for automatically transporting the sample to be tested, wherein the sample circulation bin includes a set of mechanical pushing devices for pushing the sample to be tested and a storage bin for storing the sample to be tested, and the control module is used to control the sample injection operation of the system.

Further, the standard compartment is located below the above-mentioned sample injection manipulator assembly, the length is roughly equal to the left and right operating range of the manipulator, the width is basically the same as the front and rear operating range of the manipulator, and the depth is 0~ 10mm, and the height is slightly smaller than the upper and lower running range of the robotic arm.

Further, the height of the top of the standard chamber is approximately the same as the height of the top of the sample circulation chamber.

Further, the sample circulation chamber is roughly a vertical cuboid structure, the mechanical pushing device includes a synchronous belt, two vertical links not at the same height, a centrally fixed and rotatable horizontal link, and an upper and lower telescopic device, The synchronous belt drives the two horizontal pins arranged on the diagonal to move horizontally to push the sample tray to move horizontally. One end of the horizontal connecting rod is connected, and the other end of the horizontal connecting rod is connected with the top end of the lower vertical connecting rod. The two horizontal pins, the pressing plate and the supporting plate are respectively arranged on the four corners of the vertical cuboid structure.

Further, a top plate is provided above the sample circulation chamber for pressing the sample tray to avoid displacement when the injection needle pierces the sample, and the top plate is provided with an opening corresponding to the sample position in the sample tray for The syringe is passed through to aspirate the sample.

Further, a locking device is provided at the sample injection position of the sample circulation chamber, and also includes a cold air channel for maintaining a lower temperature of the sample chamber.

Further, the control module is also used to read the sample detection signal online, select the most suitable standard sample as a reference according to the signal strength, calculate the injection time, and control the robotic arm to inject the selected standard sample.

Further, the high-throughput automatic sampling system further includes a needle washing tank for the injection needle, and a waste liquid guiding device, a flow cleaning device, a brush and an air-drying device are arranged in the needle washing tank.

Another object of the embodiments of the present invention is to provide a high-throughput automatic sampling method, the method comprising:

S1 starts the software, reads the sample sequence table provided by the user, opens a standard sample data file and starts data collection to record the concentration of each standard sample and the corresponding detection signal intensity and signal start and end time, and then begins to pair the standard sample series one by one. Each sample is injected twice. After completion, stop data collection and close the standard data file, and inject the samples to be tested (including unknown samples, QC samples, blank samples, etc.);

S2 When injecting each sample to be tested, the type and group of the sample are still read first. If the sample type is a standard, restart S1; if the sample is in the same group as the previous tested sample, then directly Proceed to the next step S3; if it is not the same group, it means that the sample has opened a new group, the software will then close the previous data file and stop the data collection, then open a new data file and restart the data collection to store the subsequent data The sample detection signal and the corresponding start and end time;

S3 draws and injects the sample to be tested, the control module reads the detection signal immediately and compares it with the signal of each of the previously stored standard sample series, thereby selecting a standard sample with the closest signal intensity as the test signal The reference of the test sample;

S4 When the injection of a sample to be tested is completed, the selected standard sample is injected immediately, and the control module stores the detection signal value and start and end time of the two injections in the opened data file.

Further, step S1 ' is also included before the start of step S2: the process of sample tray cyclic operation, including: (1) the mechanical push device pushes the stacked sample trays upward until it reaches the top plate above, and the mechanical push device returns to the original position immediately. (2) The mechanical pusher pushes the bottommost sample pan on the downward side to the bottom vacancy, and the mechanical pusher immediately returns to the original position; (3) the top sample pan Sampling and injection; (4) When a tray of samples is injected, the mechanical pusher pushes the completed sample tray to the top vacancy of the downward side, and then pushes down a vertical distance of one position.

The mechanical arm assembly provided by the invention has the advantages of simple structure, convenient and rapid operation, and can quickly complete sampling and injection. With the high-throughput automatic sampler and the sample introduction method provided by the present invention, all sampling and sample introduction operations can be completed automatically, and the sample introduction speed is fast, realizing one sample introduction in 1-5 seconds, and significantly improving the efficiency of detecting samples .

Description of drawings

1 is a structural diagram of a robotic arm assembly provided by an embodiment of the present application;

Fig. 2 and Fig. 3 are respectively the structure diagram and rear view of the robot arm assembly in Fig. 1;

Fig. 4 is another structural diagram of the robotic arm assembly in Fig. 1;

5 and 6 are partial structural diagrams of a robotic arm assembly provided by an embodiment of the present application;

7 is a partial structural diagram of a robotic arm assembly provided by another embodiment of the present application;

8 is a schematic structural diagram of a high-throughput autosampler provided by an embodiment of the present application;

9 and 10 are respectively perspective views of the sample compartment of the high-throughput autosampler provided by the present application;

11 is a rear view of the sample compartment of the high-throughput autosampler provided by the present application;

12 is a partial structural diagram of the sample compartment of the high-throughput autosampler provided by the present application;

FIG. 13 is a schematic flowchart of the high-throughput automatic sampling method provided in the present application.

detailed description

In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention, but not to limit the present invention.

An embodiment of the present invention provides a robotic arm assembly, which is used as a sample loading arm assembly of a high-throughput automatic sampler. The robotic arm in the robotic arm assembly can be XYZ trilinear, or XYR, XRZ , RYZ two linear plus one rotary axis, or XRR, RYR, RRZ one linear plus two rotary axes, or a combination of RRR three rotary axes. Preferably, an embodiment is a three-axis mechanical arm of XRZ combination, with the longest arm as the X-axis, fixed at both ends in the horizontal direction, and driven by a synchronous belt; the up-down movement is the Z-axis, which is connected to the synchronous belt of the X-axis, Use a spline shaft parallel to the X-axis to drive a vertical synchronous belt drive. Preferably, the rotating shaft is driven by a spline shaft parallel to the X-axis to drive a group of worm gears, and the rotating shaft is coupled with the Z-axis driving device at the top of the spline shaft, which can rotate under the driving of the worm gear and can be driven by the Z-axis. The driving device moves up and down under the driving, and the coupling is fixed on the Z-axis driving device by a strong magnet. The top of the rotating shaft fits snugly into a bearing fixed in the Z-axis linkage. When used in a high-throughput autosampler, the number of manipulators can be one or two. In the case of two manipulators, the two manipulators can be the same three-axis combination or different three-axis. combination. Specifically, the left and right running range of each robotic arm is 250-800mm, the front and rear running range is 40-100mm, the up-and-down running range is about 15-150mm, and the positioning accuracy is controlled at about 0.1mm, so as to achieve accurate sample injection.

Specifically, in the case of at least one linear axis, the robotic arm is preferably sleeved on a sliding rail and can move along the sliding rail, and the robotic arm is horizontally displaced by a conveyor belt controlled by a stepping motor or a servo motor. Preferably, the conveyor belt is in the shape of a crawler belt, and is provided with clamping teeth for correspondingly engaging with the clamping grooves on the mechanical arm to perform precise displacement and positioning, or the conveyor belt is provided with clamping grooves, which are set at corresponding positions on the mechanical arm. Has teeth.

Specifically, the robotic arm assembly can control the up and down displacement and axial rotation of the injection needle through the spline shaft, for example, the rotation and up and down movement of the robotic arm can be controlled synchronously through the two spline shafts, so that after the injection needle sucks the sample It can be moved to the injection port of the mass spectrometer for injection.

Specifically, for a high-throughput autosampler with two robotic arms, one of the robotic arms is used for the injection of standard samples, and the other is used for the injection of samples to be tested. In order to speed up the mechanical movement, the moving part of the robotic arm, that is, the moving arm part, must have its own weight as small as possible to reduce inertia, preferably made of lightweight materials such as aluminum alloy and titanium alloy, and the movement in all directions should be made as much as possible. The fastest transmission method, such as transmission through synchronous belt, long arm rotation and large-scale gears, etc., can improve the running speed of the robotic arm and complete a sample injection in 1-5 seconds.

In a specific embodiment, the robotic arm is an XRZ combined three-axis robotic arm, as shown in FIG. 1 , wherein the horizontal direction (the direction in which the upper slide rail 33 and the lower slide rail 34 are arranged) in FIG. 1 is the X-axis, up and down The direction is the Z axis, and each mechanical arm is set on a slide rail. The motor driven spline shaft on the end side drives the mechanical arm to move horizontally along the upper and lower rails, and drives the mechanical arm to move up and down and rotate through the synchronous belt.

Fig. 1 shows a structural diagram of a robotic arm assembly provided by an embodiment of the present application, wherein two sample injection robotic arm assemblies (4, 5) are shown. The structures of the two robotic arm assemblies are different, and the robotic arm assembly 4 is an XRZ combination The three-axis robot arm, the robot arm assembly 5 is an XR robot arm, which cannot move up and down. The two sample introduction arm assemblies (4, 5) are simultaneously arranged on a set of track structures, and the horizontal movement direction is used as the X axis, so that the sample introduction robot arm assembly 4 can also move up and down (moves along the Z axis), and can It rotates around its own axis (R axis) to complete sampling and injection by controlling the displacement of the injection needle. The end of the robotic arm assembly (4, 5) is used to set the injection needle for injection and aspiration.

In another embodiment, the two robotic arm assemblies have the same structure, and both are three-axis robotic arms combined with XRZ.

2 and 3 are the structural diagram and rear view of the robotic arm assembly in FIG. 1 , the robotic arm assembly includes the above-mentioned track structure (upper slide rail 33 and lower slide rail 34 ), and also includes an enclosure structure 1 and a drive structure. Wherein, the enclosure structure is a rectangular frame structure as a whole, which serves as the installation frame of the track structure. Both ends of the upper slide rail 33 and the lower slide rail 34 are fixedly mounted on the enclosure structure, and the drive structure is mounted on one side of the enclosure structure. The overall structure is compact and easy to install and disassemble.

3 and 4 further show the driving structure of the robotic arm assembly in the above embodiment. The drive structure includes four motor mounting blocks ( 21 , 22 , 23 , 24 ), a motor mounting piece 25 (see FIG. 1 ), a servo or stepper motor 26 , a first axis motor 27 and a second axis motor 28 . The four motor mounting pads are respectively installed on the left and right sides, and two motor mounting pads are arranged on each side, which are connected to each other through the motor mounting pieces 25 respectively. As shown in FIG. 1 , the first shaft motor 27 and the second shaft motor 28 are installed on the outside of the left end plate 12 for connecting and driving the first spline shaft 31 and the second spline shaft 32 , wherein The first spline shaft 31 , the second spline shaft 32 , the upper slide rail 33 and the lower slide rail 34 are all arranged parallel to each other. In the above structure, all drive motors are fixedly installed at the end of the X-axis and do not move with the moving arm, which not only reduces the self-weight of the moving arm, but also has no drag line, and the structure is more stable, and the movement speed can be accelerated as much as possible.

As for the robotic arm assembly 4 , the robotic arm is only sleeved on one track (the upper slide rail 33 or the lower slide rail 34 ), but is connected with the first spline shaft 31 and the second spline shaft 32 at the same time. The right ends of the first spline shaft 31 and the second spline shaft 32 are fixedly connected to the right end plate through an upper spline bearing and a lower spline bearing, respectively. The servo motor 26 penetrates through the front cover and is mounted on the motor mounting member 25 . As shown in FIG. 4 , the track structure further includes an X-axis timing belt, a timing belt driving pulley 352 , a timing belt driven pulley mounting member, a timing belt driven pulley 354 , a timing belt driven pulley screw 355 and a timing belt driven pulley washer. Both sides of the upper slide rail 33 and the lower rail 34 are respectively fixedly connected with the motor mounting pads located on the left and right sides. The servo or stepper motor 26 is connected to the synchronous belt driving pulley 352 through a rotating shaft, and drives the synchronous belt driving pulley 352 to rotate, thereby driving the X-axis synchronous belt to move, and driving the mechanical arm to slide down the upper slide rail 33 or down. Rail 34 moves. The interior of the X-axis synchronous belt is in the shape of teeth, and is driven by meshing with the synchronous belt driving pulley 352 and the synchronous belt driven pulley 354 .

FIG. 5 and FIG. 6 are enlarged schematic diagrams of a sample injection robotic arm device in an embodiment of the present invention. The sample injection mechanical arm device includes a slider mechanism, a vertical transmission structure, a compression spring 44 , a compression spring baffle 45 , a rotating arm 46 and a sample injection needle interface 47 . The slider mechanism includes an upper slider 411 , a lower slider 412 , a connection block 413 , installation sliders ( 414 , 415 , 416 , 417 , 418 , 419 ) and a short rail slider 4191 . The vertical transmission structure includes Z-axis timing belt 421, spline driving wheel 422, spline driven wheel 423, X-axis timing belt tooth plate 424, Z-axis timing belt tooth plate 425, short slide rail 426, turbine 427, screw Sleeve 428 , upper turbine bearing 4291 , lower turbine bearing 4292 , first screw bearing 4293 , second screw bearing 4294 and short splines 43 . The upper sliding block 411 and the lower sliding block 412 are respectively engaged with the upper sliding rail 33 and the lower sliding rail 34 . As shown in FIG. 5 , when the upper spline shaft 31 rotates, it drives the vertical transmission structure 42 to control the up and down movement of the manipulator; when the lower spline shaft 31 rotates, it drives the turbine 427 to rotate, thereby controlling the axial rotation of the manipulator.

FIG. 7 is a schematic structural diagram of a robotic arm assembly in another embodiment of the present invention, which shows the structure of the robotic arm assembly 5 on the left side in FIG. 1 . Compared with the manipulator shown in Fig. 5 and Fig. 6, the manipulator assembly reduces the conveyor belt device for moving up and down, and the manipulator can only rotate in the axial direction, but cannot move up and down. Specifically, the robotic arm device includes a transmission mechanism, a screw sleeve 511, a first screw bearing 512, a second screw bearing 513, a turbine 514, a fixing mechanism 52, a mounting block 521, an upper bearing 522, a lower bearing 523, a slider 524, The principle of axial rotation of the zero position plate 525, the zero position spline 53, the rotating arm 54 and the injection needle interface 55 is the same as that of the mechanical arm assembly shown in FIG. 5 and FIG. 6 .

In a specific embodiment, if a robotic arm assembly is used, the injection of the unknown sample and the aspiration of the standard sample are completed by the same robotic arm, and the operating range of the robotic arm only covers the area where the standard sample and the unknown sample are located, about 200× 200mm, preferably about 180x 150mm. If two robotic arms are used, one is used to inject unknown samples (samples to be tested) and the other is used to inject standard samples, and the coverage of each robotic arm is consistent with the size of the sample tray. The three-axis structure of the manipulator is the same as the above manipulator, and can be any combination of rotation and linear motion. The preferred structure is a combination of two spline shafts and a synchronous belt driven XRZ, which is consistent with the above embodiment. Other robotic arm structures can also be used.

FIG. 8 is a schematic structural diagram of a high-throughput autosampler provided by an embodiment of the present invention. The autosampler includes a conveyor belt for transporting the needle, and a robotic arm assembly, wherein the robotic arm assembly can snap the needle to the needle seat of the needle, or remove the needle from the needle seat up and down. Specifically, the robotic arm assembly may be the robotic arm assembly described above, or may be other combined robotic arm assemblies. In this embodiment, there is only one robotic arm, which is used to install the injection needle after sampling on the needle seat, and the injection needle that has absorbed the sample is transported from the robotic arm to the remote mass spectrometer injection port through an independent conveyor belt , the conveyor belt spans the standard sample injection area and the sample injection area to be tested, one end of which is near the injection port of the mass spectrometer, and the other end is above the sample tray. Needle holders, each needle holder is a device that allows the needle to be easily installed and removed without changing the position and stability of the needle, such as an omega-shaped clip, a "U"-shaped magnet, Or an electromagnet, etc., or a combination of these parts. When a syringe loaded with an unknown sample is delivered to the mass spectrometer inlet for injection, another syringe is just above the sample tray, and the robotic arm removes the needle and sends it to the designated standard sample suction Once the unknown sample is injected, the conveyor belt will run for half a circle immediately, and the standard sample will be sent to the empty needle of the injection port and sent to the robot arm to pick up the next sample, and so on and so on and analyze all the samples one by one. sample. The advantage of the device structure is that one injection needle is responsible for sampling, and the other injection needle is responsible for injection. Both are completed at the same time, and then the functions are replaced, and the cycle is repeated, which saves a lot of time compared to the entire cycle of sampling and injection completed by one robotic arm. Preferably, a vertical axis, the Z axis, may also be installed at the injection port of the mass spectrometer, for pushing the injection needle down into the injection port for injection. If the injection needle also functions as a mass spectrometer spray needle, the Z axis at the injection port can be omitted, because the conveyor belt can be tilted and installed at any angle, so that the injection needle can be accurately conveyed to the spray position without any other mechanism to assist. For this embodiment, the positions of the standard sample and the sample to be tested can be placed at any position within the range covered by the sampling arm, and it is preferable to place the standard sample tray and the sample injection tray of the sample to be tested separately. In the specific operation, the standard sample is concentrated in a sample injection tray and fixed in a special position to prevent the standard sample from entering the circulation chamber with the sample to be tested, thereby avoiding complicated arrangements and convenient operation.

The sample injection needle in the embodiment of the present invention is a hollow needle, which is connected with a needle pump, and is used for aspirating and injecting a sample.

Embodiments of the present invention further provide a high-throughput automatic sample injection system, including a sample injection robot arm assembly, a sample injection needle, a standard bin for placing standard samples, a sample circulation bin for automatic sample feeding, and a control module. The sample introduction manipulator assembly can be XYZ three linear, or XYR, XRZ, RYZ two linear plus one rotary axis, or XRR, RYR, RRZ one linear plus two rotary axis, or RRR three rotary axis combined manipulator assembly, preferably For the robotic arm assembly described above. The sample circulation chamber includes a set of mechanical pushing devices for pushing the samples to be tested to move and a storage chamber for storing the samples to be tested. The standard bin is located under the above-mentioned sample injection manipulator. The length is roughly equal to the left and right operation range of the manipulator, and the width is basically the same as the front and rear operation range of the manipulator. The upper and lower operating range of the arm is slightly smaller, as long as the movement of the robotic arm is not hindered. Dozens to hundreds of standard samples and quality control (QC) samples can be accommodated in the standard bin. The standard bin can also be set at the top of the sample circulation bin at approximately the same height as the sample to be tested.

In one embodiment, the storage compartment is a vertical rectangular box, the sample compartment is arranged inside, the front door is open, the periphery and the back are made of hard plates, and a top plate above presses the sample tray to make it stick to the injection needle. No displacement occurs when the sample is punctured, and the top plate has openings at locations corresponding to the sample in the sample tray for the passage of a sampling needle in order to aspirate the sample. Two stacks of overlapping sample trays can be placed in parallel in the storage bin, and a vertical partition can be added between the two stacks of sample trays to prevent the sample trays from moving to the left and right during the flow. Each stack of sampling trays can be a stack of any number of sampling trays, but the total height of the stack is preferably close to and slightly lower than the height of the matching detection instrument. For example, when used in conjunction with a mass spectrometer, the height of the mass spectrometer is generally between 400 and 750 mm, and the height of the corresponding storage bin is preferably between 350 and 700 mm. Each sample tray can hold 1 to 384 samples, and the most commonly used standard tray can hold 96 samples, which is the 96-well plate structure corresponding to the international standard. The formula for calculating the total number of sample trays stored in the sample compartment is:

Here, N is the number of sample trays that can be accommodated in the sample chamber, H is the height of the sample chamber, and h is the total height of the sample tray after the sample is loaded. For example, if the height of the sample tray plus the sample is 35mm, and the sample bin is 400mm high, then the sample bin can accommodate 20 sample trays. The tops of the left and right sides of the sample compartment each have a vacancy that is connected and slightly higher (about 1-5 mm) than the height of the sample tray containing the sample, which is used for the circulation of the sample tray. When the storage compartment door is closed, the door and back plate clamp the sample tray so that it does not move forward or backward when pushed. One of the two stacks of sample trays always moves up and the other always moves down during the cycle. The empty space at the top of the storage bin on the side that moves upward is the sample injection position. There is a locking mechanism on the front and rear vertical walls. After the sample tray is pushed into this position, it will not move up and down unless it is strongly pushed; The penultimate position on the side is also provided with a stop mechanism. When the whole stack of sample trays is pushed up to one position, even if the thrust is removed, the sample stack will not fall back automatically, leaving a vacancy at the bottom. The inner arm of the storage compartment on the lower side is equipped with a damping mechanism except the lowest position, so that the whole stack of sample trays will not slide down automatically without being pushed. The locking and backstop mechanism can be any device that allows the sample tray to go up and prevent it from going down, such as a retractable positioning pin with a spring with an inclined surface facing down, a spring positioning bead, an L-shaped back button, a cross-shaped rotating shaft, etc. The damping mechanism can be any mechanism that prevents the sample tray from automatically sliding down under its own gravity, such as roughening the inner surface of the storage bin, embedding magnetic materials on the sample tray and the inner surface of the storage bin, and so on.

The cycle operation process of the sample trays in the storage bin is as follows: (1) The mechanical push device first pushes the stacked sample trays up until they reach the top plate above, and then the mechanical push device returns to the original position, forming an empty space at the bottom of the upward side. ; (2) The mechanical pusher pushes the bottommost sample tray on the downward side to the vacant position on the upper side, and the mechanical pusher immediately returns to the original position; (3) The sample-injecting robotic arm samples the top sample tray, and each time a sample is taken After injection into the mass spectrometer, once the sample signal appears, the control module compares it with the stored standard series to select the position of the standard with the closest signal intensity, and the standard injection robotic arm immediately injects the standard. (4) When a tray of samples is completed, the mechanical push device pushes the completed sample tray to the top empty space on the lower side, and then pushes down a vertical distance of one position, at this time, there is still a space at the top. , and the bottom vacancy is filled; (5) starts the next cycle of (1) to (4).

Preferably, each sampling tray is placed in a frame box whose inner length and width are just enough to accommodate the sampling tray and the height is slightly larger than the total height of the sampling tray added to the sample container. The sampling tray can be put in and taken out freely, and the frame boxes are superimposed on each other, which can circulate in the storage bin but cannot be easily taken out from the storage bin.

Figures 9-12 show the specific structure of the sample chamber for automatic sample feeding matched with the high-throughput autosampler according to an embodiment of the present invention. 9 shows a front structural view of the sample chamber, wherein the sample chamber includes a sample enclosure 6 , a first top plate 61 , a middle baffle 62 , a second top plate 71 , a standard sample foam gasket 72 , and a standard sample box 63 . The standard sample box 63 is used to accommodate the sample to be tested. The first top plate 61 and the second top plate 71 are used to cover the standard sample box 63 to prevent displacement during sampling. The first top plate 61 and the second top plate 71 have openings at the positions corresponding to the samples in 63, which are convenient for injection needles. insertion. In Fig. 9, when the sample pan to be tested moves cyclically, the sample on the right moves upward, the sample on the left moves downward, as indicated by the arrow in the figure, and all sample pans move in one direction.

The mechanical pushing device is located behind the sample chamber, and is connected to the connecting rod push piece 64 for pushing the standard sample box 63, as shown in FIG. 10 . Both sides of the middle baffle 62 are storage bins for storing samples to be tested.

Figure 11 shows the rear view structure of the sample chamber, that is, the structure of the mechanical pushing device. The mechanical pushing device includes: a synchronous driven wheel 72, a synchronous belt 73, an electric telescopic rod 74, a vertical slider 75, a horizontal link 76 with a fixed center and rotatable at both ends, and two vertical links 77 with different heights , DC gear motor 78 and transverse push block 79 . The horizontal link 76 is connected to the ends of the two vertical links 77 to form a substantially N-shaped structure. A synchronous driving wheel 721 is provided below the DC deceleration motor 78 for driving the other three synchronous wheels, as shown in FIG. 12 . The mechanical pushing device also includes a cold gas channel 8 for maintaining the temperature of the cryogenic sample. The transverse push block 79 is provided with a transverse push pin 791 . Specifically, the drive motor (DC deceleration motor 78) drives the synchronous wheel and drives the synchronous belt to move, so that the horizontal pin (upper and lower two horizontal pins 791) connected to the synchronous belt can move horizontally, and the horizontal pin 791 in the lower right corner of FIG. 11 pushes The sample tray moves to the left, and the horizontal pin 791 in the upper left corner pushes the sample tray to the right. At the same time, the up and down driving device (electric telescopic rod 74) drives the left vertical link 77 through the connecting block, drives the right vertical link 77 to move up and down through the horizontal link 76, and the left lower vertical link 77 moves up and down. The lower end is connected to the pallet, the upper end of the higher vertical link 77 on the right side is connected to the pressing plate, the left sample tray can be held up by the holding plate, the right sample tray can be pressed down by the pressing plate, and the lifting and pressing of the sample tray can affect the sample. The left and right movement of the disc is performed synchronously or continuously. The specific working principle is: referring to Fig. 10, when the sample tray on the upper right is used up, the electric telescopic rod moves down, which drives the right pallet to move down, and the upper left pressing plate 64 moves up, and then the motor works, which drives the horizontal sales through the conveyor belt. , so that the empty sample tray is pushed to the upper left corner, the horizontal pin at the lower right corner pushes the lower left sample tray to fill the empty space in the lower right corner, and then the electric telescopic rod is reset, the upper left pressing plate 64 presses down the empty sample tray, and the lower right corner support plate supports the right tray to fill the empty space in the upper right corner.

Specifically, the injection needle needs to be cleaned after sampling, and the time required for traditional automatic sampler to wash the needle is often more than the time for aspirating and injecting the sample. In the embodiment of the present invention, dynamic needle washing is adopted. The specific method is: A needle washing tank is set on the path of the sample needle returning to the sample area. The waste liquid diversion, flowing cleaning solution, brush and air drying device are set in the tank. When the sample injection is completed, the sample needle is quickly sent to the sample area. The remaining sample solution and the needle washing solution in the needle pump are quickly pushed into the needle washing tank, and at the same time, the sampling needle quickly reversely swipes through the cleaning solution, brush, and air-drying air flow in the tank, and it has been completely cleaned when it reaches the sample area. It is clean and there is no residual liquid left on the surface, and the needle washing time is not increased at all. The test shows that the sample residue can be reduced to less than 0.1% after dynamic needle washing.

Another embodiment of the present invention provides a method for high-throughput automatic sample injection through an automatic sampler. As shown in FIG. 13 , the method is implemented by the above-mentioned high-throughput automatic sample introduction system. Specifically, after the system is started, it is initialized first, and the mass spectrometry control software and the sample table are started at the same time, then the sample sequence table provided by the user is read, a standard sample data file is opened, and data collection of the standard sample is started to record each standard The concentration of the sample and the corresponding detection signal intensity and signal start and end time, and then start to inject each sample of the standard sample series twice. sample, QC sample, blank sample, etc.) injection (step S1).

Before each sample to be tested is injected, the software first reads the sample group information from the sample table. If the sample does not belong to the same group as the previously injected sample, the sample is a new group. Immediately trigger the data acquisition and storage switch, record and store the subsequent process, and then start the robotic arm to sample and inject samples; if it is not the same group, directly start the robotic arm to sample and inject samples. The purpose of this is to store the detection signals of all classified samples (same group) in one data file, which not only greatly reduces the number of data files but also facilitates subsequent data processing. In the specific operation, when injecting each sample to be tested, the type and group of the sample are still read first. If the sample type is a standard, repeat the above step S1; if the sample is the same as the previous tested sample group, then go to the next step S3; if it is not the same group, it means that the sample has opened a new group, the software will close the previous data file and stop the data acquisition, then open a new data file and start again Data collection in order to store subsequent sample detection signals and corresponding start and end times (step S2);

During the sampling process, the robotic arm moves down first, sucks about 10 μL of air, then sucks the sample, and then moves to the right to the mass spectrometer injection port, and the robotic arm descends to spray. Store the peak heights and start and end times corresponding to the sample detection results, then clean the sample injection needle on the robotic arm, wait for it after cleaning, and prepare to repeat the above sample injection steps

In step S3, the operation of drawing and injecting the sample to be tested is not performed, wherein the control module immediately reads the detection signal and compares it with the signal intensity of each of the previously stored standard sample series, thereby selecting a signal with the closest signal intensity. The standard sample serves as the reference for the sample to be tested.

Step S4 is: after the injection of a sample to be tested is completed, the selected standard sample is injected immediately, and the control module stores the detection signal values and start and end times of the two injections in the opened data file.

Specifically, after injecting the sample to be tested, the detection system calculates the sample concentration to determine the position of the standard sample, and then performs standard injection. According to the calculated position of the standard, the robotic arm moves to the corresponding position and absorbs the standard. Then spray injection, the system stores the peak height and start and end time of the standard after injection, the robotic arm moves to the needle washing port to wash the needle, and then terminates the injection operation. After that, the mass spectrometer stores the data file and fills in the sample sheet, ending all operations.

Further, before the start of step S2, it also includes step S1': a process of cyclic operation of the sample tray, and the process of this cyclic operation is as described above.

In the high-throughput automatic sample injection method provided by the present invention, by setting one or two automatic robotic arms and an automatic needle washing device, large-scale sample injection can be fully automated, and the sample tray is automatically circulated by setting an automatic storage bin , which improves the injection efficiency.

The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements and improvements made within the principles of the present invention shall be included in the protection scope of the present invention. Inside.

Claims

A sample introduction manipulator assembly, comprising a manipulator and a first spline shaft, the manipulator comprising a vertical shaft and a horizontal moving arm, one end of the horizontal moving arm is vertically and fixedly or detachably connected to the vertical shaft, and The horizontal moving arm is rotatable around the vertical axis, and the other end of the horizontal moving arm is provided with a needle mount for the injection needle, and the rotation of the vertical axis is driven by the first spline shaft driving the worm gear.
The sample introduction robot arm assembly according to claim 1, wherein the rotation of the first spline shaft is driven by a first drive motor, and the first drive motor is arranged on the side of the first spline shaft. end.
The sample introduction robotic arm assembly according to claim 1, further comprising a slide rail, a second spline shaft, a horizontal conveyor belt and a vertical conveyor belt, the robotic arm is sleeved on the slide rail, the The horizontal conveyor belt controls the horizontal movement of the mechanical arm, the vertical conveyor belt is sleeved on the second spline shaft and controls the up and down movement of the mechanical arm, the second spline shaft is driven by the second drive motor, the The second drive motor is arranged at the end of the second spline shaft, the horizontal conveyor belt is driven by a third drive motor, and the third drive motor is arranged at the end of the slide rail.
The sample introduction robotic arm assembly according to claim 1, wherein the robotic arm is made of lightweight materials such as aluminum alloy, titanium alloy, carbon fiber, etc., or a combination thereof.
The sample introduction robot arm assembly according to claim 1, wherein the sample introduction robot arm assembly comprises two robot arms, the structures of the two robot arms are the same or different, one is used for injecting standard samples, and the other is used for injecting standard samples. Inject the sample to be tested.
A sample-injecting robot arm assembly for simultaneously injecting a standard sample and a sample to be tested, the sample-injecting robot arm assembly includes a robot arm for installing and removing an injection needle, and a horizontal conveyor belt separated from the robot arm , the horizontal conveyor belt spans the standard sample injection area and the sample injection area to be tested, and the two equalization points are respectively equipped with a needle seat for a injection needle, and the mechanical arm is used to install the injection needle on the onto the needle seat described above and remove the needle from the needle seat.
A high-throughput automatic sampling system, comprising a sampling robotic arm assembly, the sampling robotic arm assembly is XYZ three linear, or XYR, XRZ, RYZ two linear plus a rotation axis, or XRR, RYR, RRZ - linear The combined manipulator assembly with two rotating axes, or RRR three rotating axes, also includes the injection needle installed on the needle seat of the manipulator, the standard compartment for placing the standard sample, and the sample circulation compartment and control for automatically transporting the sample to be tested. module, wherein the sample circulation chamber includes a set of mechanical pushing devices for pushing the sample to be tested to move and a storage chamber for storing the sample to be tested, and the control module is used to control the operation of the sample introduction system.
The high-throughput automatic sample introduction system according to claim 7, wherein the sample introduction robot arm assembly is the sample introduction robot arm assembly according to any one of claims 1-6.
The high-throughput automatic sample injection system according to claim 7 or 8, wherein the standard chamber is located below the sample injection robot arm assembly, the length is approximately equal to the left and right operation range of the robot arm, and the width is the same as that of the robot arm. The front and rear running ranges are the same, the depth is 0-10mm larger than the limit of the downward movement of the mechanical arm, and the height is slightly smaller than the upper and lower running range of the mechanical arm.
The high-throughput automatic sampling system according to claim 7 or 8, wherein the height of the top of the standard compartment is approximately the same as the height of the top of the sample circulation compartment.
The high-throughput automatic sampling system according to claim 7 or 8, wherein the sample circulation chamber is substantially a vertical cuboid structure, the mechanical pushing device comprises a synchronous belt, and two vertical The connecting rod and a centrally fixed and rotatable horizontal connecting rod and an upper and lower telescopic device, the synchronous belt drives the two horizontal pins arranged diagonally to move horizontally to push the sample tray to move horizontally, and the vertical connecting rod with a higher height The top end is provided with a pressing plate for pressing down the sample tray, the bottom end is connected with one end of the horizontal connecting rod, and the other end of the horizontal connecting rod is connected with the top end of the lower vertical connecting rod. The bottom end of the straight connecting rod is provided with a support plate for lifting the sample tray upwards, and the two horizontal pins, the pressure plate and the support plate are respectively arranged on the four corners of the vertical cuboid structure.
The high-throughput automatic sampling system according to claim 7 or 8, characterized in that, a top plate is arranged above the sample circulation chamber for pressing the sample tray to avoid displacement when the injection needle pierces the sample, and the top plate There are openings on the top corresponding to the sample positions in the sample tray for the passage of the sample needle to draw the sample. 13. A high-throughput automatic sampling method, the method comprising:

S1 records the concentration of each standard sample and the corresponding detection signal intensity and signal start and end time, and then injects each standard sample twice;

S2 reads the type and group of each sample to be tested. If the sample type is a standard product, repeat step S1; if the sample is a tested sample, go directly to the next step S3; if the sample to be tested is an untested sample If the sample is detected, the data collection will be restarted, and the detection signal of the sample to be tested and the corresponding start and end times will be stored;

S3 sucks and injects the sample to be tested, the control module reads the detection signal immediately and compares it with the signal of the previously stored standard sample one by one, and selects a standard sample with the closest signal intensity as the reference for the sample to be tested;

S4 injects the selected standard sample, and stores the detection signal value and start and end time of the injection correspondingly.
The high-throughput automatic sampling method according to claim 13, wherein the step S1 further includes a process of circulating the sample tray, including:

(1) The mechanical push device pushes the stacked sample trays upward until it reaches the top plate above, and the mechanical push device returns to its original position immediately, forming a bottom vacancy at the bottom of the upward side;

(2) The mechanical pusher flatly pushes the bottommost sample tray to the bottom vacancy, and the mechanical pusher immediately returns to its original position;

(3) Sampling and injecting the top sample tray;

(4) After a tray of samples is injected, the mechanical push device pushes the completed sample tray to the top empty space on the downward side, and then pushes down a vertical distance of one position.