JP2002243637A - Sensor utilizing total reflection attenuation, and measurement chip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily exchange a measurement chip to an optical system for measurement, without using any refractive index matching liquid in a sensor which utilizes total reflection attenuation. SOLUTION: The measurement chip 10 is composed by forming a dielectric block 11 having a surface 11a, where a metal film 12 is formed, and a light incident end face 11b and an emission end face 11c of a light beam and a sample retention section 13 for retaining a sample 15 on the metal film 12 in one piece. Furthermore, a magnet 10a is provided at the bottom, while a turntable 20 for supporting the measurement chip 10 has a ferromagnetic body 20a that is attracted with a magnet 10a of the measurement chip 10 at a measurement chip support position.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sensor utilizing attenuated total reflection, such as a surface plasmon sensor for quantitatively analyzing a substance in a sample utilizing the generation of surface plasmon, and a measuring chip used for the sensor. It is.

[0002]

2. Description of the Related Art In a metal, free electrons vibrate collectively to generate a compression wave called a plasma wave. And, the quantization of this compression wave generated on the metal surface is
It is called surface plasmon.

Conventionally, various surface plasmon sensors for quantitatively analyzing a substance in a sample by using the phenomenon that surface plasmons are excited by light waves have been proposed.
Among them, a particularly well-known one uses a system called a Kretschmann configuration (see, for example, JP-A-6-167443).

A surface plasmon sensor using the above-described system basically includes, for example, a dielectric block formed in a prism shape, a metal film formed on one surface of the dielectric block and brought into contact with a sample, and a light beam. The light source to be generated and the light beam are set at various angles with respect to the dielectric block so that total reflection conditions can be obtained at the interface between the dielectric block and the metal film, and that total reflection attenuation due to surface plasmon resonance can occur. And an optical system for measuring the intensity of the light beam totally reflected at the interface and detecting the state of surface plasmon resonance, that is, the state of attenuated total reflection.

In order to obtain various incident angles as described above, a relatively narrow light beam may be incident on the interface at a different incident angle, or a component incident on the light beam at various angles. May be incident on the interface in a convergent light state or a divergent light state. In the former case, the light beam whose reflection angle changes according to the change in the incident angle of the incident light beam is detected by a small photodetector that moves in synchronization with the change in the reflection angle, or the direction in which the reflection angle changes. Can be detected by an area sensor extending along. On the other hand, the latter case can be detected by an area sensor extending in a direction in which all light beam components reflected at various reflection angles can be received.

In the surface plasmon sensor having the above structure, when a light beam is made incident on a metal film at a specific incident angle θ _SP equal to or larger than the total reflection angle, an evanescent wave having an electric field distribution is formed in a sample in contact with the metal film. Is generated, and surface plasmons are excited at the interface between the metal film and the sample by the evanescent wave. When the wave number vector of the evanescent light is equal to the wave number of the surface plasmon and the wave number matching is established, both are in a resonance state, and the energy of light is transferred to the surface plasmon. The intensity of the reflected light drops sharply. This decrease in light intensity is generally detected as a dark line by the light detection means.

[0007] The above resonance occurs only when the incident beam is p-polarized. Therefore, it is necessary to set in advance so that the light beam is incident as p-polarized light.

When the wave number of the surface plasmon is known from the incident angle θ _{SP at} which the attenuated total reflection (ATR) occurs, the dielectric constant of the sample is obtained. That is, the wave number of the surface plasmon is K
_{When SP} and the angular frequency of the surface plasmon are ω, c is the speed of light in vacuum, ε _m and ε _S are the metal and the dielectric constant of the sample, respectively, the following relationship is obtained.

[0009]

(Equation 1) Knowing the dielectric constant epsilon _S of the sample, since it is found the concentration of a specific substance in the sample based on a predetermined calibration curve or the like, after all, by knowing the incident angle theta _SP that the reflected light intensity decreases, the sample dielectric Properties related to the index, or refractive index, can be determined.

As similar sensors utilizing attenuated total reflection (ATR), for example, “Spectroscopy”, Vol. 47, No. 1 (1998), pp. 21-23 and 26-27.
A leak mode sensor described on the page is also known. This leak mode sensor is basically formed of, for example, a dielectric block formed in a prism shape, a clad layer formed on one surface of the dielectric block, and formed on the clad layer and brought into contact with a sample. An optical waveguide layer, a light source for generating a light beam, and the light beam with respect to the dielectric block, a condition of total reflection is obtained at an interface between the dielectric block and the cladding layer, and the light is guided by the optical waveguide layer. An optical system that enters at various angles so that total reflection attenuation can occur due to wave mode excitation, and the intensity of the light beam totally reflected at the interface is measured to determine the excited state of the waveguide mode, that is, the total reflection attenuation state. And a light detecting means for detecting.

In the leakage mode sensor having the above configuration,
When the light beam is incident on the cladding layer through the dielectric block at an incident angle equal to or greater than the total reflection angle, only light having a specific wave number at a specific incident angle is transmitted through the cladding layer. The light propagates in a guided mode. When the waveguide mode is excited in this way, most of the incident light is taken into the optical waveguide layer, so that total reflection attenuation occurs in which the intensity of light totally reflected at the interface sharply decreases.
Since the wave number of the guided light depends on the refractive index of the sample on the optical waveguide layer, the refractive index of the sample and the characteristics of the sample related thereto are analyzed by knowing the specific incident angle at which the total reflection attenuation occurs. be able to.

In a conventional surface plasmon sensor or leaky mode sensor using the above system, in practice, it is necessary to change the thin film layer to be brought into contact with the sample every measurement. Therefore, conventionally, this thin film layer is fixed to a flat plate-shaped dielectric block, and a prism-shaped dielectric block as an optical coupler for causing the total reflection is separately provided separately from the thin film layer. The former method of integrating the dielectric block on one side has been adopted. In that case, the latter dielectric block should be fixed to the optical system, and the former plate-like dielectric block to which the thin film layer is fixed should be used as a measurement chip, and only this measurement chip should be replaced for each sample. Becomes possible.

[0013]

However, in the case of using the replaceable conventional measuring chip, a gap is generated between the plate-shaped dielectric block and the prism-shaped dielectric block, and the refractive index becomes discontinuous. Therefore, it is necessary to integrate these two dielectric blocks via a refractive index matching liquid. The operation of integrating the two dielectric blocks in such a manner is very complicated, and therefore, the conventional measurement chip is not easy to handle at the time of measurement. In particular, when the measurement chip is automatically loaded on a turret or the like and the turret is rotated, the measurement chip is automatically supplied to a measurement position for receiving the light beam to automate the measurement. It takes time to remove, which tends to hinder the improvement of the efficiency of automatic measurement.

The present invention has been made in view of the above circumstances, and does not require the use of a refractive index matching liquid, and can easily be replaced with a measuring optical system using attenuated total reflection. And a measurement chip.

[0015]

SUMMARY OF THE INVENTION A sensor utilizing attenuated total reflection according to the present invention comprises a light source for generating a light beam, a dielectric block transparent to the light beam, and formed on one surface of the dielectric block. A measuring chip having a thin film layer and a sample holding mechanism for holding a sample on the thin film layer, a support for supporting the measuring chip at a predetermined position, and passing the light beam through the dielectric block. And an optical system that enters at various angles so as to obtain the condition of total reflection at the interface with the thin film layer, and a light for measuring the intensity of the light beam totally reflected at the interface to detect the state of attenuated total reflection. A sensor utilizing total reflection attenuation, comprising: a detection block, wherein the dielectric block includes one of an input end face, an output end face of the light beam, and one surface on which the thin film layer is formed. The measuring chip is formed by integrally forming the dielectric block, the thin film layer, and the sample holding mechanism, and the measuring chip and the support are provided with a magnet on one of the support base and the other. And a magnet or a ferromagnetic material mutually attracting the magnet.

Further, another sensor utilizing attenuated total reflection according to the present invention is particularly configured as the above-mentioned surface plasmon sensor, and includes a light source for generating a light beam, and a dielectric material transparent to the light beam. Body block, a thin film layer made of a metal film formed on one surface of the dielectric block, a measuring chip provided with a sample holding mechanism for holding a sample on the thin film layer, and a support base for supporting the measuring chip at a predetermined position And an optical system for passing the light beam through the dielectric block at various angles so as to obtain a total reflection condition at an interface between the dielectric block and the metal film;
A sensor using a total reflection attenuation accompanying surface plasmon resonance, comprising: a light detection unit that measures the intensity of the light beam totally reflected at the interface and detects a state of the total reflection attenuation, wherein the sensor uses the total reflection attenuation. The body block is formed as one block including all of the incident end face, the outgoing end face of the light beam, and one surface on which the thin film layer is formed, and the measuring chip includes the dielectric block, the thin film layer, and the sample holder. The mechanism is integrally formed, and one of the measurement chip and the support is provided with a magnet, and the other is provided with a magnet or a ferromagnetic material that attracts the magnet to each other. Things.

Still another sensor utilizing attenuated total reflection according to the present invention is particularly configured as the above-mentioned leaky mode sensor, and includes a light source for generating a light beam, and a light source transparent to the light beam. A dielectric block, a measurement chip having a thin film layer formed on one surface of the dielectric block and a sample holding mechanism for holding a sample on the thin film layer, and a support base for supporting the measurement chip at a predetermined position,
An optical system for passing the light beam through the dielectric block at various angles so as to obtain a total reflection condition at an interface between the dielectric block and the thin film layer; and an intensity of the light beam totally reflected at the interface. And a light detection means for detecting a state of attenuated total reflection, comprising a sensor using attenuated total reflection accompanying excitation of a waveguide mode in the optical waveguide layer, wherein the dielectric block is And the measuring chip is formed as one block including all of the incident end face, the outgoing end face of the light beam, and one surface on which the thin film layer is formed, and the measuring chip is integrated with the dielectric block, the thin film layer, and the sample holding mechanism. One of the measurement chip and the support table is provided with a magnet, and the other is provided with a magnet or a ferromagnetic material that attracts the magnet to each other. It is intended to.

In the above-mentioned sensor utilizing the total reflection attenuation, a sensing medium which interacts with a specific component in the sample may be arranged on the thin film layer.

The measuring chip of the present invention is a measuring chip used for a sensor using attenuated total reflection,
A dielectric block, a thin film layer formed on one surface of the dielectric block, and a sample holding mechanism for holding a sample on the thin film layer are integrally formed, and provided on a support for supporting the measurement chip. The magnet or the ferromagnetic material is provided at a position where the magnet or the ferromagnetic material attracts each other.

The magnet may be embedded in a part of the dielectric block in advance and integrally formed, or may be a magnet in which a ferromagnetic substance is embedded first and then magnetized to be magnetized. There may be. Further, the magnet may be provided in any part of the measuring chip as long as it does not hinder the measurement.

The thin film layer may be formed of a metal film and used for a sensor utilizing attenuated total reflection accompanying surface plasmon resonance. The thin film layer may be formed of a clad layer formed on one surface of the dielectric block. And an optical waveguide layer formed thereon, and may be used for a sensor that utilizes attenuation of total reflection accompanying excitation of a waveguide mode in the optical waveguide layer.

Further, in the measuring chip of the present invention,
A sensing medium that interacts with a specific component in the sample may be disposed on the thin film layer.

As a material suitable for forming the measurement chip, for example, glass or transparent resin can be used.

[0024]

According to the sensor utilizing attenuated total reflection according to the present invention, the dielectric block includes a single block including all of the incident surface, the exit surface of the light beam, and the surface on which the metal film is formed. As described above, it has an incident surface and an exit surface for a light beam, and therefore also functions as an optical coupler). The dielectric block, the thin film layer formed on one surface thereof, and the Since the sample holding mechanism for holding the sample on the thin film layer is integrally formed, the measurement chip can be easily exchanged only by attaching and detaching the measurement chip to and from the optical system.

That is, unlike the prior art, it is not a configuration in which another dielectric block is integrated with a dielectric block as a single optical coupler fixed to an optical system. Therefore, it is not necessary to integrate them through a liquid crystal, and poor handling properties due to the use of the refractive index matching liquid can be eliminated.

Further, since the magnet is provided on one side of the measuring chip or the supporting stand supporting the same and the other is provided with a magnet or a ferromagnetic material attracting the magnet, the measuring chip is easily fixed to a predetermined position of the supporting stand. During the measurement, the attractive force by the magnetic force acts during the measurement, so that the measurement can be stably performed without changing the position of the measurement chip.

[0027]

Embodiments of the present invention will be described below in detail with reference to the drawings. FIG. 1 shows an overall shape of a sensor using attenuated total reflection according to a first embodiment of the present invention. The sensor according to the first embodiment is configured as the surface plasmon sensor described above. FIG. 2 shows a side view of a main part of the apparatus.
FIG. 3 shows a perspective shape of the measuring chip 10.

As shown in FIG. 1, the surface plasmon sensor includes a turntable 20, which is a support for supporting a plurality of measurement chips 10, and a semiconductor laser or the like for generating a measurement light beam (laser beam) 30. A laser light source 31,
Condensing lens 32 constituting the incident optical system, photodetector 40,
A support driving means 50 for intermittently rotating the turntable 20, and a controller 60 for controlling the driving of the support driving means 50 and receiving the output signal S of the photodetector 40 and performing the processing described later. And an automatic sample supply mechanism 70.

As shown in FIGS. 2 and 3, the measuring chip 10 has a rectangular parallelepiped outer shape formed of, for example, a transparent resin or the like. The sample holder 13 is shaped like a letter, and the lower part is the dielectric block 11. The container-shaped bottom surface of the sample holder 13 is one surface 11a of the dielectric block 11, on which a metal film 12 made of, for example, gold, silver, copper, aluminum or the like is formed. Further, a magnet 10a is integrally embedded in a part of the bottom surface of the measurement chip 10. That is, the measurement chip 10 has a surface 11a on which the metal film 12 is formed.
A dielectric block 11 composed of one block including an incident end face 11b and an exit end face 11c of the light beam;
And a sample holder 13 for holding the sample on the metal film are integrally formed, and are replaceable with respect to the turntable 20. Preferable examples of the transparent resin as the material of the measurement chip 10 include PMMA, polycarbonate, amorphous polyolefin, cycloolefin and the like. Glass is also suitable as another material. In general, it is desirable to use a material having a refractive index in the range of about 1.45 to 2.5 as a material for forming the dielectric block 11. The reason is that a practical SPR resonance angle can be obtained in this refractive index range. The sample holder 13 contains, for example, a liquid sample as described later.
15 are stored. In this example, the sensing medium 14 is fixed on the metal film 12, which will be described later.

The magnet 10a of the measurement chip 10 may be a magnet in which a permanent magnet is embedded in advance, or a magnet made by applying a high magnetic field after embedding a ferromagnetic material. Is also good.

As shown in FIG. 4, the turntable 20 is provided with a ferromagnetic material 20a for attracting the magnet 10a of the measurement chip 10 at a predetermined position for supporting each measurement chip (other portions are not shown). Non-magnetic material), measuring tip 10 from below
An opening 20b is provided for allowing a light beam to be incident on the incident end face 11b, and detecting the light beam reflected at the interface and emitted from the emission end face 11c by the lower light detecting means. Further, the ferromagnetic material 20a embedded in the turntable 20 may be a magnet attracting the magnet 10a of the measurement chip 10.

A plurality of turntables 20 (12 in this example)
) Are configured to be supported at equal angular intervals on a circumference around the rotation axis 20a. The support driving means 50 is composed of a stepping motor or the like, and rotates the turntable 20 intermittently by an angle equal to the arrangement angle of the measurement chip 10.

The condenser lens 32 has a light beam as shown in FIG.
30 is condensed and passed through the dielectric block 11 in a convergent light state,
Light is incident on the interface 11a between the dielectric block 11 and the metal film 12 so that various incident angles can be obtained. The range of the incident angle is an angle range in which the condition of total reflection of the light beam 30 at the interface 11a is obtained and surface plasmon resonance is generated.

The light beam 30 enters the interface 11a as p-polarized light. In order to do so, the laser light source 31 may be disposed in advance so that the polarization direction thereof becomes a predetermined direction. Alternatively, the direction of polarization of the light beam 30 may be controlled by a wave plate or a polarizing plate. Note that the optical system such as the condenser lens 32 may be configured to make the light beam 30 incident on the interface 11a in a defocused state. By doing so, errors in detecting the state of surface plasmon resonance (for example, measuring the position of the dark line) are averaged, and measurement accuracy is improved.

The photodetector 40 is composed of a line sensor in which a large number of light receiving elements are arranged in one line, and the light receiving elements are arranged such that the arrangement direction of the light receiving elements is the direction of arrow X in FIG. .

On the other hand, the controller 60 is
Receives an address signal A indicating the rotation stop position, and outputs a drive signal D for operating the support driving means 50 based on a predetermined sequence. The controller 60 includes a signal processing unit 61 that receives the output signal S of the photodetector 40, and a display unit 62 that receives an output from the signal processing unit 61.

The automatic sample supply mechanism 70 includes, for example, a pipette 71 for sucking and holding a liquid sample by a predetermined amount, and a pipette 71.
Means for moving the sample from the sample container 73 set at a predetermined position to the pipette 71 by suction and holding the sample in the sample holding portion 13 of the measurement chip 10 at a predetermined stop position. The sample is supplied dropwise.

Hereinafter, a sample analysis by the surface plasmon sensor having the above-described configuration will be described. At the time of sample analysis, the turntable 20 is intermittently rotated by the support driving means 50 as described above. Then, the sample 15 is supplied by the automatic sample supply mechanism 70 to the sample holding unit 13 of the measurement chip 10 which is stopped at a predetermined position when the turntable 20 stops.

After that, when the turntable 20 is rotated several times and then stopped, the measuring chip 10 holding the sample 15 in the sample holding section 13 is moved to a position where the light beam 30 is incident on the dielectric block 11. Position (measurement tip 10 on the right in FIG. 2)
At the position (). In this state, the laser light source 31 is driven by a command from the controller 60, and the light beam 30 emitted from the laser light source 31 is incident on the interface 11a between the dielectric block 11 and the metal film 12 in a state of being converged as described above. I do. The light beam 30 totally reflected at the interface 11a is a light detector
Detected by 40.

The light beam 30 is incident on the interface 11a so as to obtain various incident angles, and is totally reflected at the interface 11a. Therefore, the reflected light beam 30 has components reflected at various reflection angles. Will be included.

When the light beam 30 is totally reflected as described above, an evanescent wave seeps from the interface 11a to the metal film 12 side. When the light beam 30 enters the interface 11a at a specific incident angle θ _SP , the evanescent wave resonates with the surface plasmon excited on the surface of the metal film 12, so that the reflected light intensity I drops sharply. FIG. 5 schematically shows the relationship between the incident angle θ and the reflected light intensity I when this total reflection attenuation phenomenon occurs.

Therefore, the light amount detection signal output from the photodetector 40 is
Check the amount of light detected for each light receiving element from signal S to detect dark lines.
The incident angle (total reflection attenuation)
Angle) θ _SPAnd input the reflected light intensity I obtained in advance.
Based on the relationship curve with the angle of incidence θ, the specific substance in sample 15
Quantitative analysis can be performed. Controller 60 signal processing
The part 61 determines the specific substance in the sample 15 based on the above principle.
The quantity is analyzed, and the analysis result is displayed on the display unit 62.

When the measurement is performed only once for one sample 15, the measurement is completed by the above operation, and the measurement chip 10 having completed the measurement is manually operated from the turntable 20 or an automatic discharging means is provided. It may be used and discharged. On the other hand, when performing measurements on one sample 15 multiple times,
After the measurement is completed, keep the measurement chip 10 as it is on the turntable 20
If you support it after one turn of the turntable 20,
The sample 15 held on the measurement chip 10 can be measured again.

As described above, this surface plasmon sensor is configured such that a plurality of measurement chips 10 are supported on a turntable 20, and the turntable 20 is moved to sequentially arrange the measurement chips 10 at measurement positions. Therefore, the samples 15 held by the sample holding portions 13 of the plurality of measurement chips 10 can be sequentially used for the measurement as the turntable 20 moves. Thus, according to this surface plasmon sensor, it is possible to perform measurement on a large number of samples 15 in a short time.

In this embodiment, the dielectric block 11 and the metal film
The measurement chip 10 is configured by integrating the sample holder 12 with the sample holder 13, and the measurement chip 10 can be replaced with a turntable 20. By removing the new measurement chip 10 from the table 20 and supporting it on the turntable 20, new samples 15 can be successively used for measurement, and the measurement of many samples 15 can be performed in a shorter time. become.

In this measuring chip 10, it is necessary to optically couple a dielectric block provided with a metal film with another dielectric block serving as an optical coupler via a refractive index matching liquid, as has been conventionally done. Since it is not available, it is easy to handle and convenient for replacement. In addition, since the ferromagnetic material on the support base is easily positioned at a predetermined position by the attractive force of the magnet, and then fixed by the magnetic force, stability does not occur at the time of measurement without displacement and the like. high. In particular, even when the turntable 20 is rotated a plurality of times and the same sample is measured a plurality of times, a highly reliable measurement can be performed because the position of the measurement chip does not shift.

The sensing medium 14 fixed on the surface of the metal film 12 binds to a specific substance in the sample 15. Examples of such a combination of the specific substance and the sensing medium 14 include an antigen and an antibody. In that case, the antigen-antibody reaction can be detected based on the total reflection attenuation angle θ _SP .

Next, a second embodiment of the present invention will be described with reference to FIG. FIG. 6 shows a surface plasmon resonance measurement chip 10 'according to a second embodiment of the present invention and a side surface shape of a main part of a surface plasmon sensor using the same. In FIG. 6, elements that are the same as the elements in FIG. 2 are given the same reference numerals, and descriptions thereof will be omitted unless otherwise necessary (the same applies hereinafter).

The measuring chip 10 ′ according to the second embodiment
Is different from the measuring chip 10 shown in FIGS. 2 and 3 only in that the sensing medium 14 is omitted. Therefore, in this case, the specific substance in the sample 15 is not bound to the sensing medium 14, and the substance to be measured in the sample 15 is usually quantitatively analyzed.

Except for the points described above, the measuring chip 10 'has the same configuration as the measuring chip 10 shown in FIGS. 2 and 3. Therefore, even when this measuring chip 10' is used,
The same effect as when the measurement chip 10 is used can be obtained.

Next, a third embodiment of the present invention will be described with reference to FIGS. 7 and 8 show a side surface shape and a plane shape of the surface plasmon sensor of the third embodiment, respectively, and FIG. 9 shows a side surface shape of a main part thereof.

The surface plasmon sensor of this embodiment is
A measurement chip 10 similar to the measurement chip used in the above-described first embodiment is used. However, unlike the device of the above-described first embodiment, as shown in FIG.
40 is not arranged below the turntable 20 ', but is arranged above. Therefore, unlike the turntable 20 shown in FIG. 4, the turntable 20 'does not require an opening for transmitting the light beam 30. On the other hand, in order to make the light beam 30 from the light source 31 incident on the interface 11a from the side surface of the measurement chip 10, a mirror 91 is provided in the incident optical system, and the light beam 30 emitted from the light source 31 is condensed by the condenser lens 32.
And is reflected by the mirror 91 to enter the interface 11a. The optical system on the side of the photodetector 40 includes a mirror 92 and a collimator lens 93, and the light beam 30 totally reflected at the interface is reflected by the mirror 92, is collimated by the collimator lens 93, and is collimated. Received. The output signal S of the photodetector 40
Is input to the signal processing unit 61 of the controller 60 (see FIG. 6) and is provided for sample analysis. The sample analysis based on the output signal S is performed in the same manner as described in the first embodiment.

As shown in FIGS. 8 and 9, in this surface plasmon sensor, a turntable 12 is used.
At a predetermined position at an angle interval of 30 °, a groove 120b is formed to fit with the measuring chip 10, and a ferromagnetic material 120a (or a magnet) is embedded in a part of the groove 120b. This groove 120b
Thereby, the tip can be easily and more accurately positioned when the measuring chip 10 is replaced. Once positioned, the tip is fixed to a predetermined position on the turntable by the magnetic force of the magnet 10a of the measuring chip 10 and does not change its position.

In this embodiment, the turntable 120 is intermittently rotated in the direction of arrow Y by 30 °, and when the turntable 120 stops, the four measurements of the turntable 120 are performed. The chips are sequentially stopped at the positions indicated by the measurement chip supply position P1, the sample supply position P2, the measurement position P3, and the measurement chip discharge position P4 in FIG.

The measurement chip 10 taken out by the chip supply means 76 is supplied to the measurement chip supporting portion which is stationary at the measurement chip supply position P1 from the cassette 75 accommodating a plurality of measurement chips 10. Note that the chip supply means 76
It is composed of a known air suction cup and a mechanism for moving the same, for example, by sucking out and taking out the measuring chips 10 one by one from a takeout port provided at the bottom of the cassette 75, and moving it. It can be supplied to the measurement chip support section.

The sample is supplied to the measuring chip 10 supported by the measuring chip supporting portion which is stationary at the sample supply position P2 by using the automatic sample supply mechanism 70.

For the measurement chip 10 supported by the measurement chip supporting portion that is stationary at the measurement position P3, the sample held by the measurement chip 10 is analyzed using the surface plasmon resonance measuring means 77. Is made. This sample analysis will be described later with reference to FIG.

The measuring chip 10 supported by the measuring chip supporting portion which is stationary at the measuring chip discharging position P4 is discharged from the turntable 120 by the chip discharging means 78. The measurement chip support emptied in this way is
Next, when the turntable 120 is rotated by 90 °, it stops at the measurement chip supply position P1, and thereafter, the same processing as described above is repeated.

As described above, in this embodiment,
Measuring chips from cassette 75 containing multiple measuring chips 10
By providing the chip supply means 76 for taking out one by one and supplying it in a state of being supported by the turntable 120, the operation of supplying the measurement chips is streamlined, and a large number of samples 15 are provided.
The time required for the measurement can be sufficiently reduced.

Further, in each of the embodiments described above, a rotating turntable is used as a support for supporting the measurement chip, but the shape and the moving method of the support are not limited to this. For example, the support table that supports a plurality of measurement chips may be configured to move linearly in a reciprocating manner, and the plurality of measurement chips may be sequentially set in the measurement unit with the movement.

In this case, when it is necessary to perform a plurality of measurements on one sample, a plurality of measurement units each including an optical system for irradiating a measurement chip with a light beam and light detection means may be provided. For example, with the movement of the support, the measuring chips are sequentially set in the measuring section, and the measurement can be performed in each measuring section. Alternatively, only one such measurement unit is provided, the support is moved in one direction, the measurement chip is set in the measurement unit, and after the measurement is performed, the support is moved in the opposite direction to remove the measurement chip. It may be set in the measuring section again to perform the measurement.

The method of moving the support in the normal and reverse directions can be applied to the case where the above-described turntable 20 is used. When the turntable 20 is used, it is also possible to provide a plurality of measuring units so as to measure one measurement chip a plurality of times while the turntable 20 makes one rotation.

Next, a fourth embodiment of the present invention will be described with reference to FIG. The sensor using the attenuated total reflection according to the fourth embodiment is the leaky mode sensor described above, and uses an integrated measurement chip 10 ″ similarly to the case of the above-described surface plasmon sensor. In, the dielectric block which is the bottom of the container
A cladding layer 42 is formed on one surface 11a of the substrate 11, and an optical waveguide layer 43 is further formed thereon.

The measurement chip 10 ″ is formed using, for example, a synthetic resin or an optical glass such as BK7, as in the case of the first embodiment described above.
It is formed in a thin film shape using a dielectric material having a lower refractive index than the dielectric block 11 or a metal such as gold. The optical waveguide layer 43
Is a dielectric material having a higher refractive index than the cladding layer 42, for example, PM
This is also formed into a thin film using MA. The thickness of the cladding layer 42 is, for example, 36.5 n when formed from a gold thin film.
m, the thickness of the optical waveguide layer 43 is, for example, about 700 nm when formed from PMMA.

In the leakage mode sensor having the above configuration,
When the light beam 30 emitted from the light source 31 is incident on the cladding layer 42 through the dielectric block 11 at an incident angle equal to or larger than the total reflection angle, the light beam 30 is generated at the interface 11a between the dielectric block 11 and the cladding layer 42. Light of a specific wave number that is totally reflected but transmitted through the cladding layer 42 and incident on the optical waveguide layer 43 at a specific incident angle propagates through the optical waveguide layer 43 in a guided mode.
When the waveguide mode is excited in this manner, most of the incident light is taken into the optical waveguide layer 43, so that total reflection attenuation occurs in which the intensity of light totally reflected at the interface 11a sharply decreases.

Since the wave number of the guided light in the optical waveguide layer 43 depends on the refractive index of the sample 15 on the optical waveguide layer 43, the specific incident angle at which the attenuated total reflection occurs is known.
It is possible to analyze the refractive index of 15 and the characteristics of the sample 15 related thereto.

Also in this case, since an integral measuring chip is used and the magnetic chip is fixed to a turntable as a support using the magnetic force of a magnet, the same effects as those of the other embodiments can be obtained. . Note that a sensing medium that binds to a specific substance in the sample 15 may be provided on the optical waveguide layer 43.

The measuring chip used in the sensor using the attenuated total reflection according to the present invention can be formed in a shape other than the above-described one. 11 to 14 show a measuring chip according to another embodiment of the present invention.

The measuring chip according to the fifth embodiment shown in FIG.
Reference numeral 130 denotes, for example, a shape formed by cutting out a part of a quadrangular pyramid made of the transparent resin as described above, and an upper portion (an upper portion when arranged in a used state as shown in the figure).
The same applies to the following). This measuring chip 130
A sample holding hole 133 having a circular cross section whose diameter gradually decreases from the upper surface to the lower side is formed at the upper portion of the sample holding portion, and a metal film 132 is formed on the bottom surface of the sample holding hole 133. Is formed. The lower part of the sample holding portion of the measurement chip 130 is a dielectric block 131, and the bottom surface of the sample holding hole 133 is one surface 11 of the dielectric block 131.
a. 2 of 4 sides of dielectric block 131
The surfaces are a light incident end surface 131b and a light exit end surface 131c, respectively. These light entrance end face 131b and light exit end face 131c
May be formed entirely transparent, or may be formed transparent only in a partial area through which the light beam passes. Remaining 2
The two side surfaces may be formed similarly to the light incident surface 131b and the light emitting surface 131c, or may be formed translucent. A magnet 130a is embedded in the bottom of the measuring chip 130.

On the other hand, the turntable 140 as a chip support of the surface plasmon sensor using the measuring chip 130 has a square chip holding groove 142 at a predetermined position as shown in the figure. The tip holding groove 142 has a tapered shape whose cross-sectional shape gradually increases in accordance with the outer shape of the measuring chip 130. The turntable 140 is made of a ferromagnetic material that attracts magnets.

The bottom of the measuring chip 130 is fitted into the chip holding groove 142 and positioned at a predetermined position on the turntable, and is fixed by a magnetic force acting between the magnet 130a of the measuring chip 130 and the turntable.

The measuring chip according to the sixth embodiment shown in FIG.
150 has the same outer shape as the measurement chip 130 shown in FIG. 11, and has an upper portion provided with a sample holder 153, and a lower portion provided with a surface 151a on which a metal film 152 is disposed, a light incident end surface 151b, and a light output end surface 151c. This is a dielectric block 151. Furthermore, this measuring chip 1
50 has a groove 155 at the bottom and a magnet 1 in a part of the groove 155.
50a becomes embedded.

On the other hand, a turntable 140 which is a chip support for a surface plasmon sensor using this measuring chip 150 has a groove 155 at the bottom of the measuring chip 150 as shown in the figure.
Are formed at predetermined positions. The projection 162 is formed of a ferromagnetic material.

The measurement chip 150 is positioned by fitting the groove 155 into the projection 162 on the turntable 160, and the magnet 150 a and the projection 162 made of a ferromagnetic material are held in close contact with the turntable 160. Is done.

The measuring chip of the seventh embodiment shown in FIG.
170 has the same outer shape as the measurement chip 130 shown in FIG. This is the body block 171. However, the magnet 170a is completely embedded in the chip.

On the other hand, a turntable 180 as a chip support for a surface plasmon sensor using the measurement chip 170 has a chip holding groove 182 at a predetermined position, and a ferromagnetic material 180a is embedded in a part of the groove 182. I get it.

The bottom of the measuring chip 170 is fitted into the chip holding groove 182 and is positioned at a predetermined position on the turntable. The magnet 170a of the measuring chip 170 and the holding groove 18
It is fixed by the magnetic force acting between the second ferromagnetic material 180a.
As described above, even if the magnet 170a and the ferromagnetic material 180a are not in close contact with each other, the measuring chip 170 can be stably supported as long as the magnets 170a and the ferromagnetic material 180a are at a distance where a sufficient attractive force is applied to each other.

The measuring chip according to the eighth embodiment shown in FIG.
190 is a flange on the upper side of the measuring tip 130 shown in FIG.
196 is provided, and similarly, the upper part is a sample holder 193,
The lower part is a dielectric block 191 having a surface 191a on which the metal film 192 is arranged, a light incident end surface 191b, and a light exit end surface 191c. Also, this measuring tip 190 is not a bottom part but a flange 19
This is a configuration in which a magnet 190a is embedded in the lower part of 6.

The turntable 200 of the surface plasmon sensor using the measurement chip 190 has a square chip holding hole 202 as shown in the figure. The tip holding hole 202 has a tapered shape whose cross-sectional shape gradually increases upward in accordance with the outer shape of the measuring chip 130. Further, a ferromagnetic material 200a is buried in a portion adjacent to two sides of the rectangular chip holding hole 202.

The measuring tip 190 is provided with the tip holding hole 192.
The upper part is inserted into the upper part and fitted together, and the vertical position is defined by the flange part 196, and the magnet 190a embedded in the lower part of the flange part 196 and the ferromagnetic body 200a on the turntable 200 are held in close contact with each other. Fixed.

Although the measuring chips of the fifth to eighth embodiments have a metal film and have been described as an example used for a surface plasmon sensor, a cladding layer and an optical waveguide are used instead of the metal film. If a thin-film layer including two layers is provided, it can be used as a measurement chip of a leaky mode sensor.

In the above description, the measurement chip has a magnet and the turntable as the support has a ferromagnetic material. However, the measurement chip has a ferromagnetic material instead of the magnet.
The turntable as the support may be provided with a magnet. Further, the shape of the measurement chip is not limited to the shape shown in the above embodiment, and the magnet (or ferromagnetic material) does not hinder the light beam from entering and exiting the dielectric block, Any location may be provided as long as the location attracts the magnet (or ferromagnetic material).

Each of the measuring chips described in each of the above embodiments has a magnet or a ferromagnetic material at a predetermined location, so that it can be organized using magnetic force. Handling convenience is improved.
Further, the light incident end face and the output end face (measurement face) of the dielectric block of the measurement chip and the other face (non-measurement face) can be easily distinguished and arranged in one direction.

[Brief description of the drawings]

FIG. 1 is an overall view of a surface plasmon sensor according to a first embodiment of the present invention.

FIG. 2 is a partially cutaway side view showing a main part of the surface plasmon sensor of FIG. 1;

FIG. 3 is a perspective view showing a measuring chip according to the first embodiment of the present invention.

FIG. 4 is a top view showing a turntable of the surface plasmon sensor according to the first embodiment of the present invention.

FIG. 5 is a graph showing a schematic relationship between an incident angle of a light beam in a surface plasmon sensor and a light intensity detected by a photodetector.

FIG. 6 is a partially cutaway side view showing a main part of a surface plasmon sensor using a surface plasmon resonance measurement chip according to a second embodiment of the present invention.

FIG. 7 is a partially cutaway side view showing another example of the surface plasmon sensor using the surface plasmon resonance measurement chip of the present invention.

FIG. 8 is a side sectional view showing a surface plasmon resonance measurement chip according to a third embodiment of the present invention.

FIG. 9 is a perspective view showing a surface plasmon resonance measurement chip according to a fourth embodiment of the present invention.

FIG. 10 is a perspective view showing a surface plasmon resonance measurement chip according to a fifth embodiment of the present invention.

FIG. 11 is a perspective view showing a measuring chip and a support according to a fifth embodiment of the present invention.

FIG. 12 is a side sectional view showing a measuring chip and a support according to a sixth embodiment of the present invention.

FIG. 13 is a side sectional view showing a measuring chip and a support according to a seventh embodiment of the present invention.

FIG. 14 is a side sectional view showing a measuring chip and a support according to an eighth embodiment of the present invention.

[Explanation of symbols]

 10, 10 'Measuring chip 10a Magnet 11 Dielectric block 11a Interface between dielectric block and metal film 11b Light incident surface of dielectric block 11c Light emitting surface of dielectric block 12 Metal film 13 Sample holder 14 Sensing medium 15 Sample 20 Turntable 20a Ferromagnetic material 30 Light beam 31 Laser light source 32 Condensing lens 40 Photodetector 50 Support driving means 60 Controller 61 Signal processing unit 62 Display unit 70 Automatic sample supply mechanism 130, 150, 170, 190 Measurement chip 130a , 150a, 170a, 190a Magnet 131, 151, 171, 191 Dielectric block 132, 152, 172, 192 Metal film 133, 153, 173, 193 Sample holder 140, 160, 180, 200 Turntable

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) G01N 35/10 G01N 35/06 A (72) Inventor Takashi Ito 1-324 Uetakecho Fuji, Omiya City, Saitama Fuji F term (reference) 2G057 AA02 AB04 AB07 AC01 BA01 BB06 DB05 HA04 2G058 AA01 CC14 CC17 CD04 EA11 ED03 GA02 2G059 AA05 BB04 DD12 EE02 EE05 FF11 GG01 GG04 JJ11 JJ13 JJ19 KK04 KK01

Claims (8)

[Claims] A light source for generating a light beam, a dielectric block transparent to the light beam, a thin film layer formed on one surface of the dielectric block, and a sample holding mechanism for holding a sample on the thin film layer A measurement chip comprising: a support table for supporting the measurement chip at a predetermined position; and A sensor using attenuated total reflection, comprising: an optical system for incidence at various angles; and light detection means for measuring the intensity of the light beam totally reflected at the interface and detecting a state of attenuated total reflection. Wherein the dielectric block includes all of an incident end face, an exit end face of the light beam, and one surface on which the thin film layer is formed.
The measurement chip is formed as one block, wherein the dielectric block, the thin film layer and the sample holding mechanism are integrally formed, and one of the measurement chip and the support is provided with a magnet, and the other is provided with a magnet. A sensor utilizing attenuated total reflection, further comprising a magnet or a ferromagnetic material mutually attracting the magnet. 2. A light source for generating a light beam, a dielectric block transparent to the light beam, a thin film layer made of a metal film formed on one surface of the dielectric block, and a sample held on the thin film layer A measurement chip provided with a sample holding mechanism, a support table for supporting the measurement chip at a predetermined position, and the light beam passing through the dielectric block, and a total reflection condition at an interface between the dielectric block and the metal film. An optical system for incidence at various angles as obtained, and a light detecting means for measuring the intensity of the light beam totally reflected at the interface and detecting a state of attenuated total reflection. A sensor using the total reflection attenuation, wherein the dielectric block includes all of an incident end face, an exit end face, and one surface on which the thin film layer is formed of the light beam.
The measurement chip is formed as one block, wherein the dielectric block, the thin film layer and the sample holding mechanism are integrally formed, and one of the measurement chip and the support is provided with a magnet, and the other is provided with a magnet. A sensor using attenuated total reflection, comprising a magnet or a ferromagnetic material mutually attracting the magnet. 3. A light source for generating a light beam, a dielectric block transparent to the light beam, a cladding layer formed on one surface of the dielectric block, and an optical waveguide layer formed thereon. A thin film layer, a measurement chip provided with a sample holding mechanism for holding a sample on the thin film layer, a support for supporting the measurement chip at a predetermined position, and the light block passing through the dielectric block, An optical system for entering at various angles so as to obtain the condition of total reflection at the interface between the thin film layer and the thin film layer; A sensor using total reflection attenuation accompanying excitation of a waveguide mode in the optical waveguide layer, comprising: a detection unit, wherein the dielectric block includes an incident end face, an exit end face, and 1 containing all one surface layer is formed
The measurement chip is formed as one block, wherein the dielectric block, the thin film layer and the sample holding mechanism are integrally formed, and one of the measurement chip and the support is provided with a magnet, and the other is provided with a magnet. A sensor utilizing attenuated total reflection, comprising a magnet or a ferromagnetic material mutually attracting the magnet. 4. The method according to claim 1, wherein a sensing medium that interacts with a specific component in the sample is disposed on the thin film layer. sensor. 5. A measurement chip used for a sensor utilizing attenuated total reflection, comprising: a dielectric block; a thin film layer formed on one surface of the dielectric block; and a sample holding mechanism for holding a sample on the thin film layer. Wherein the magnet or the ferromagnetic material is provided at a place where the magnet or the ferromagnetic material provided on the support for supporting the measurement chip attracts the magnet or the ferromagnetic material. 6. The measurement chip according to claim 5, wherein the thin film layer is a metal film, and is used for a sensor using attenuated total reflection accompanying surface plasmon resonance. 7. The thin film layer includes a cladding layer formed on one surface of the dielectric block and an optical waveguide layer formed thereon, and attenuated total reflection accompanying excitation of a waveguide mode in the optical waveguide layer. 6. The measuring chip according to claim 5, wherein the measuring chip is used for a sensor utilizing the method. 8. The measuring chip according to claim 5, wherein a sensing medium that interacts with a specific component in the sample is disposed on the thin film layer.