JP2003139687A - Measurement chip aggregate and measurement chip take- out apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To carry a plurality of measurement chips used for a measuring apparatus that utilizes total reflection attenuation in a mass, and to easily supply a sample to the measurement chips simultaneously. SOLUTION: Each specific number of measurement chips 10 are aligned in vertical and horizontal directions, and are accommodated in a package 5 so that they can be taken out, thus composing the measurement chip aggregate 1.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a set of measuring chips used in a measuring apparatus using attenuation of total reflection, such as a surface plasmon resonance measuring apparatus for quantitatively analyzing a substance in a sample by utilizing generation of surface plasmons. It is about the body.

The present invention also relates to a device for taking out a measuring chip from an assembly of such measuring chips.

[0003]

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

Conventionally, various surface plasmon resonance measuring devices have been proposed for quantitatively analyzing a substance in a sample by utilizing the phenomenon that the surface plasmon is excited by a light wave. Among them, one that is particularly well known is one that uses a system called Kretschmann arrangement (see, for example, JP-A-6-167443).

A surface plasmon resonance measuring apparatus using the above system basically comprises, 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. A light source for generating a beam and a dielectric block that directs the light beam to the dielectric block at the interface between the dielectric block and the metal film so that various incident angles including the surface plasmon resonance condition can be obtained. And an optical system for measuring the intensity of the light beam totally reflected at the interface to detect the state of surface plasmon resonance.

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

In the surface plasmon resonance measuring apparatus having the above structure, when a light beam is incident on the metal film at a specific incident angle θ _SP which is equal to or greater than the total reflection angle, an electric field distribution is generated in the sample in contact with the metal film. An evanescent wave is generated, and the surface plasmon is excited at the interface between the metal film and the sample by the evanescent wave. When the wave 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 the light is transferred to the surface plasmon, so that at the interface between the dielectric block and the metal film. The intensity of the reflected light sharply decreases. This decrease in light intensity is generally detected as a dark line by the light detecting means.

The above resonance occurs only when the incident beam is p-polarized. Therefore, it is necessary to set in advance 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 this attenuated total reflection (ATR) occurs, the dielectric constant of the sample can be obtained. That is, the wave number of the surface plasmon is K
_{Let SP be} the angular frequency of the surface plasmons be ω, c be the speed of light in a vacuum, ε _m and ε _s be the metal, and the permittivity of the sample respectively, and the following relationships are established.

[0010]

[Equation 1] If the permittivity ε _s of the sample is known, the concentration of the specific substance in the sample can be known based on a predetermined calibration curve, etc., so that the incident angle θ _SP (decay angle of total reflection) at which the reflected light intensity eventually decreases.
By knowing, the specific substance in the sample can be quantitatively analyzed.

In the conventional surface plasmon resonance measuring apparatus using the above system, in practice, it is necessary to replace the metal film in contact with the sample every measurement. Therefore, conventionally, this metal film is fixed to a flat plate-shaped dielectric block, and a prism-shaped dielectric block as an optical coupler for producing the above-mentioned total reflection is provided separately from the fixed dielectric block. The method of integrating the former dielectric block on one side was adopted. By doing so, the latter dielectric block can be fixed to the optical system, and the former dielectric block and the metal film can be used as a measurement chip, and only this measurement chip can be replaced for each sample. .

Further, as a similar measuring apparatus utilizing the attenuated total reflection (ATR), for example, "Spectroscopic Research" Vol. 47, No. 1 (1998), pages 21 to 23 and 26 to 27.
Leakage mode measuring devices described on the page are also known. This leak mode measuring device is basically a dielectric block formed, for example, in a prism shape, a clad layer formed on one surface of the dielectric block, and a clad layer 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 incident on the dielectric block at various angles so that total reflection conditions can be obtained at the interface between the dielectric block and the cladding layer. The optical system is provided with an optical system and a light detecting means for measuring the intensity of the light beam totally reflected at the interface and detecting the excited state of the guided mode, that is, the attenuated state of total reflection.

In the leaky mode measuring device having the above structure,
When a light beam is incident on the cladding layer through the dielectric block at an angle of incidence equal to or more than the total reflection angle, only light with a specific incident angle having a specific wave number is transmitted in the optical waveguide layer after passing through the cladding layer. It propagates in the guided mode. When the guided mode is excited in this manner, most of the incident light is taken into the optical waveguide layer, so that the total reflection attenuation occurs in which the intensity of the 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, knowing the specific incident angle (total reflection attenuation angle) at which attenuation of total reflection occurs, the refractive index of the sample and the related The characteristics of the sample can be analyzed.

When using this leaky mode measuring device, as in the case of using the surface plasmon resonance measuring device described above, one dielectric block is fixed to the optical system of the device while another dielectric block is used. It is possible to form a clad layer and an optical waveguide layer on the to form a measurement chip, and replace only this measurement chip for each sample.

By the way, in the case of using the replaceable conventional measuring chip, in order to prevent a discontinuity in the refractive index due to a gap between the dielectric block and the prismatic dielectric block. However, it becomes necessary to integrate both of these dielectric blocks via a refractive index matching liquid. In this way, the work of integrating the two dielectric blocks is very complicated, so that this conventional measuring chip is not easy to handle during measurement. In particular, when the measurement chip is automatically loaded on the turret or the like and the turret is rotated to automatically supply the measurement chip to the measurement position where the light beam is received, the measurement chip is loaded, It takes time and trouble to remove it, which tends to hinder the efficiency of automatic measurement.

Further, since this conventional measuring chip uses a refractive index matching liquid, it is feared that the measuring chip may adversely affect the environment.

In view of the above circumstances, the present applicant has previously proposed a measuring chip which does not require the use of a refractive index matching liquid and which can be easily replaced with a measuring optical system (Japanese Patent Application No. 2000-242242). 2001-92666).

This measuring chip comprises a dielectric block, a thin film layer formed on one surface of the dielectric block and brought into contact with a sample, a light source for generating a light beam, and the light beam for the dielectric block. The total reflection condition at the interface between the dielectric block and the thin film layer, and an optical system that makes the light incident so that various incident angle components are included, and the total intensity of the light beam totally reflected at the interface is measured. In a measuring chip used in a measuring apparatus utilizing attenuated total reflection, comprising: a light detecting means for detecting a state of reflective attenuation, wherein the dielectric block comprises an incident surface, an emitting surface of the light beam and the thin film layer. Including all of the one side where the
It is formed as one block, and the thin film layer is integrated with this dielectric block.

When the measuring chip is for measuring the surface plasmon resonance, the thin film layer is composed of a metal film, and for measuring leak mode, the thin film layer is a cladding layer and an optical waveguide. Composed of layers.

In the dielectric block constituting the measuring chip, it is preferable that a space above a surface on which the thin film layer is formed is laterally surrounded and a liquid reservoir for holding a sample is defined on the one surface. The formed part is formed.

[0021]

By the way, in immunological analysis, a liquid sample is often placed in a container generally called a well plate and handled. This well plate has small wells, that is, a predetermined number of liquid reservoirs vertically and horizontally (for example, 8 × 12 = 96, 16 × 24 = 384).
The wells are arranged side by side and are used for sample supply, transport, etc. by storing a liquid sample in each well. Even when the above-mentioned surface plasmon resonance measuring device or the like is used for immunological analysis, use of such a well plate makes handling of a liquid sample very convenient.

When the above well plate is used in the field of sample analysis, it is general to use a dedicated sample supply means adapted to it. That is, for example, when using a well plate having 8 × 12 = 96 wells, a sample supply having eight liquid pipettes arranged at the same pitch as the arrangement pitch of eight wells in one row A liquid sample is dispensed from these pipettes into 8 wells at the same time, and the operation is repeated 12 times so that the liquid sample is supplied to all 96 wells.

The sample supply means as described above is already widely used in sample analysis sites of companies, hospitals, various research institutes, etc.
Even when the measuring chip shown in No. 92666 is used, it is extremely convenient in practice if such a sample supply means can be used as it is. Moreover, even if the existing sample supply means cannot be used as it is,
If a plurality of measurement chips can be collectively transported or samples can be supplied to them at the same time, the efficiency of sample analysis work can be expected to improve.

In view of the above circumstances, the present invention has an object to provide a measuring chip assembly which makes it possible to easily convey a plurality of measuring chips together and to simultaneously supply samples to them. And

A further object of the present invention is to provide a measuring chip take-out device which can take out a measuring chip easily and surely from the above-mentioned measuring chip assembly.

[0026]

One measuring chip assembly according to the present invention is a measuring chip shown in Japanese Patent Application No. 2001-92666 mentioned above, that is, a dielectric block and is formed on one surface of the dielectric block. A thin film layer that is brought into contact with the sample, a light source that generates a light beam, and the light beam with respect to the dielectric block have total reflection conditions at the interface between the dielectric block and the thin film layer, and Measurement using attenuation of total reflection, which comprises an optical system for making the light incident so as to include an incident angle component, and a light detection means for measuring the intensity of the light beam totally reflected at the interface to detect the state of attenuation of total reflection. A measuring chip used in an apparatus, wherein the dielectric block includes all of an incident surface of the light beam, an emission surface facing the incident surface, and one surface on which the thin film layer is formed. Is formed as a single block,
This dielectric block is a collection of measurement chips in which the thin film layers are integrated. A plurality of measurement chips are arranged in a predetermined number in each of the vertical and horizontal directions, and are housed in a package so that they can be taken out. It is characterized by that.

Further, another measuring chip assembly according to the present invention is formed especially for the above-mentioned surface plasmon resonance measuring apparatus, and is formed on a dielectric block and one surface of this dielectric block to form a sample. A thin film layer made of a metal film to be brought into contact, a light source for generating a light beam, the light beam with respect to the dielectric block, a total reflection condition at an interface between the dielectric block and the metal film, and An optical system for making light incident so as to include various incident angle components,
A measuring chip used in a measuring apparatus utilizing attenuated total reflection, comprising: a light detection unit that measures the intensity of the light beam totally reflected at the interface and detects the state of attenuation of total reflection due to surface plasmon resonance. The dielectric block includes all of an incident surface of the light beam, an emission surface facing the incident surface, and one surface on which the thin film layer is formed.
This is a group of measurement chips formed as one block, in which the thin film layer is integrated with the dielectric block. A plurality of measurement chips can be taken out by arranging a predetermined number in each of the plurality of vertical, horizontal directions. It is characterized by being housed in a package.

Still another measuring chip assembly according to the present invention is formed especially for the leaky mode measuring device described above, and includes a dielectric block and a cladding layer formed on one surface of the dielectric block. And a thin film layer formed on the optical waveguide layer, which is brought into contact with the sample, a light source for generating a light beam, the light beam to the dielectric block, the dielectric block and the clad layer. The condition of total reflection at the interface with and the optical system that is incident so that various incident angle components are included, and the intensity of the light beam totally reflected at the interface are measured to determine the waveguide mode of the optical waveguide layer. A measuring chip for use in a measuring apparatus utilizing attenuated total reflection, comprising: a photodetection means for detecting a state of attenuation of total internal reflection due to excitation, wherein the dielectric block is A measurement chip formed by integrating the thin film layer into a dielectric block, which is formed as a single block including all of the incident surface, the exit surface facing the incident surface, and the one surface on which the thin film layer is formed. A plurality of the measurement chips are arranged in a predetermined number in the vertical and horizontal directions, and are housed in a package so that they can be taken out.

In the measuring chip assembly of the present invention described above, a plurality of measuring chips are independently housed in the package, for example, one by one. Alternatively, a plurality of measurement chips may be connected in one of the vertical and horizontal directions to form a chip row, and the chip rows may be arranged in the other vertical or horizontal direction and housed in the package.

Further, in the measuring chip assembly of the present invention,
When the dielectric block has a shape obtained by cutting out a part of a substantially polygonal pyramid, the package may be provided with a rib that abuts a side surface of the dielectric block and defines a position of the dielectric block. desirable.

Further, in the measuring chip assembly according to the present invention, it is desirable that the bottom plate of the package is formed with a through hole through which the bottom surface of the measuring chip arranged thereon can be seen.

On the other hand, the measuring chip take-out device according to the present invention is intended for a measuring chip assembly having a package in which a through hole is formed in the bottom plate, and is measured by entering the package through the through hole. It is characterized in that a member for pushing up the bottom surface of the chip is provided.

[0033]

EFFECTS OF THE INVENTION The measuring chip assembly according to the present invention comprises a plurality of measuring chips arranged in a predetermined number in the vertical and horizontal directions and housed in a package so as to be taken out. According to this, it becomes possible to easily transport a plurality of measurement chips together and to simultaneously supply samples to them. In the analysis of the sample, the measuring chips can be taken out one by one, or in the case where a plurality of measuring chips are connected, can be taken out in units of the number of connections, so that there is no hindrance to the analysis.

If the vertical and horizontal arrangement pitches of the measuring chips in the package are matched with the well arrangement pitches in the well plate described above, the existing sample supply means for this kind of well plate can be used as it is. It can also be used for supplying a sample to a measurement chip.

Further, in the measuring chip assembly of the present invention,
When the dielectric block has a shape obtained by cutting out a part of a substantially polygonal pyramid, and the package includes a rib that abuts a side surface of the dielectric block and defines the position of the dielectric block, Since the measuring chips are defined in the vertical direction and the lateral direction, it is possible to prevent a problem that some of the measuring chips are misaligned in the package and the sample is improperly supplied.

Further, in the measuring chip assembly of the present invention, if a through hole is formed on the bottom plate of the package so that the bottom surface of the measuring chip disposed on the package can be seen, an appropriate member can be provided from this through hole. By inserting the measuring chip into the package and pushing up the bottom surface of the measuring chip, the measuring chip can be easily and reliably taken out from the package.

Since the measuring chip take-out device according to the present invention is provided with the member for pushing up the bottom surface of the measuring chip as described above, the measuring chip take-out device is used to easily and surely take the measuring chip from the package. , And it will be possible to take out automatically.

[0038]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 1 shows a measurement chip assembly 1 according to a first embodiment of the present invention, and an overall shape of a surface plasmon resonance measuring apparatus for performing measurement using a measurement chip 10 taken out from the measurement chip assembly 1. ,
FIG. 2 shows a side surface shape of a main part of this device. First,
The surface plasmon resonance measuring device will be described.

As shown in FIG. 1, this surface plasmon resonance measuring apparatus includes a turntable 20 supporting a plurality of measuring chips 10, a laser light source 31 such as a semiconductor laser for generating a light beam (laser beam) 30 for measurement. , A condenser lens 32 forming an incident optical system, a photodetector 40, a support body drive means 50 for intermittently rotating the turntable 20, and a drive of the support body drive means 50, It has a controller 60 that receives the output signal S of the photodetector 40 and performs processing described later, and an automatic chip supply mechanism 70.

As shown in FIGS. 2 and 3, the measuring chip 10 has, for example, a transparent dielectric block 11 having a shape in which a part of a quadrangular pyramid is cut off, and gold, silver, etc. formed on the upper surface of the dielectric block 11. Film made of copper, copper, aluminum, etc.
It is composed of a metal sample 12 and a cylindrical sample holding frame 13 which defines a space closed on the side of the metal film 12. The dielectric block 11 has a surface 11a on which the metal film 12 is formed (a surface forming an interface described later) and a surface 11 on which the light beam 30 is incident.
It is formed as one block including all b and the surface 11c from which the light beam 30 is emitted. A liquid sample 15, for example, is stored in the sample holding frame 13 as described later.

Dielectric block 11 constituting the measuring chip 10
Also, the sample holding frame 13 is integrally molded using transparent resin and is replaceable with respect to the turntable 20. To be replaceable, for example, turntable 20
In the through hole 20H (see FIG. 2) formed in the measurement chip 10
May be fitted and held.

Preferred examples of the transparent resin include cycloolefin polymer, PMMA, polycarbonate, amorphous polyolefin and the like. Further, “ZEONEX 330R” (trade name), which is one of cycloolefin polymers manufactured by Nippon Zeon Co., Ltd., can be mentioned as a very preferable one.

In this example, the sensing medium 14 is fixed on the metal film 12, which will be described in detail later. Further, as a material for forming the dielectric block 11, it is generally desirable to use a material having a refractive index in the range of about 1.45 to 2.5. The reason is that a practical SPR resonance angle can be obtained in this refractive index range.

A plurality of turntables 20 (11 in this example)
The individual measurement chips 10 are configured to be supported at equal angular intervals on the circumference around the rotation shaft 20a. The support body driving means 50 is composed of a stepping motor or the like, and intermittently rotates the turntable 20 by an angle equal to the arrangement angle of the measuring tip 10.

The condenser lens 32, as shown in FIG.
30 is focused and passed through the dielectric block 11 in a convergent light state, and the interface between the dielectric block 11 and the metal film 12 (hereinafter, this interface is referred to as the same number as the one surface 11a of the dielectric block 11 for convenience sake). 11a "), so that various incident angles can be obtained. The range of this incident angle is
The condition of total reflection of the light beam 30 is obtained at 11a, and
The range includes an angle range in which surface plasmon resonance can occur.

The light beam 30 is incident on the interface 11a in the p-polarized state. In order to do so, the laser light source 31 may be arranged in advance so that the polarization direction thereof is the predetermined direction. In addition, the polarization direction of the light beam 30 may be controlled by a wave plate or a polarizing plate.

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

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

The chip automatic supply mechanism 70 includes, for example, a lateral guide rail 71 extending in one direction, a lateral moving portion 72 that moves along the lateral guide rail 71 in the direction of arrow X, and a lateral moving portion.
A vertical guide rail 73 fixed to 72, a vertical moving portion 74 that moves along the vertical guide rail 73 in the arrow Y direction, and a pair of gripping arms that open and close, for example, are fixed to the vertical moving portion 74. And a chip gripper 75. A chip push-up member 76 that interlocks with the chip gripping portion 75 in the X and Y directions is arranged below the chip gripping portion 75. These chip gripper 75 and chip lifting member
Reference numeral 76 constitutes a measuring chip take-out device according to the present invention, and each of them is vertically movable by a driving means (not shown).

Hereinafter, sample analysis by the surface plasmon resonance measuring apparatus having the above-mentioned structure will be described. During sample analysis, the turntable 20 has the support driving means 50 as described above.
It is rotated intermittently by. And turntable
The automatic chip feeding mechanism 70 inserts the measuring chip assemblies 1 to 1 into the through-holes 20H that have come to the predetermined positions when the 20 stops.
A single measuring chip 10 is provided. In the sample holding frame 13 of each measuring chip 10 which constitutes this measuring chip assembly 1,
The liquid sample 15 is supplied in advance.

Regarding the supply of the measurement chip assembly 1 and the measurement chip 10 by the automatic chip supply mechanism 70,
It will be described in detail later.

After that, when the turntable 20 is rotated several times and then stopped, the measurement chip 10 holding the sample 15 in the sample holding frame 13 is measured by the light beam 30 entering the dielectric block 11. Position (Measurement tip 10 on the right side in Fig. 2)
It will be stationary 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. To do. The light beam 30 totally reflected at the interface 11a is a photodetector.
Detected by 40.

Since the light beam 30 is incident on the dielectric block 11 in the convergent light state as described above, it includes components that are incident on the interface 11a at various incident angles θ. The incident angle θ is set to an angle equal to or larger than the total reflection angle. Therefore, the light beam 30 is totally reflected at the interface 11a, and the reflected light beam 30 contains components that are reflected at various reflection angles. Here, the optical system such as the condenser lens 32,
The light beam 30 may be configured to be incident on the interface 11a in a defocused state. By doing so, the error in the state detection of the surface plasmon resonance (for example, the position measurement of the dark line) is averaged, and the measurement accuracy is improved.

When the light beam 30 is totally reflected as described above, an evanescent wave seeps out from the interface 11a toward the metal film 12 side. When the light beam 30 is incident on 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, and therefore the reflected light intensity of this light is increased. I sharply decreases. Note that FIG. 4 schematically shows the relationship between the incident angle θ and the reflected light intensity I when the attenuation phenomenon of total reflection occurs.

Therefore, the light amount detection signal output from the photodetector 40 is detected.
From the signal S, the amount of light detected for each light receiving element is checked to detect the dark line.
The above incident angle (total reflection attenuation
Angle) θ _SPAnd 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
It can be quantitatively analyzed. Signal processing of controller 60
The part 61 determines the specific substance in the sample 15 based on the above principle.
The quantity analysis is performed, and the analysis result is displayed on the display unit 62.

When the measurement is carried out only once for one sample 15, the measurement is completed by the above-mentioned operation. Therefore, the measurement tip 10 after the measurement is manually operated from the turntable 20 or by the automatic discharging means. It can be used and discharged. On the other hand, when the measurement is performed multiple times for one sample 15,
Even after the measurement is completed, the measuring tip 10 remains the turntable 20.
If it is supported by, after one turn of the turntable 20,
The sample 15 held on the measuring chip 10 can be subjected to the measurement again.

As described above, in this surface plasmon resonance measuring apparatus, the plurality of measuring chips 10 are arranged on the turntable 20.
The sample 15 held in each sample holding frame 13 of the plurality of measurement chips 10 is supported by the sample holder 15 by moving the turntable 20 and sequentially arranging the measurement chips 10 in the measurement position. The turntable 20 can be used for measurement one after another as the turntable 20 moves. As a result, according to this surface plasmon resonance measuring apparatus, it is possible to measure a large number of samples 15 in a short time.

This measuring chip 10 does not need to optically couple the dielectric block 11 to another dielectric block through the refractive index matching liquid as has been conventionally done. Therefore, this measuring chip 10 is easy to handle and can be made unrelated due to the adverse effect of the refractive index matching liquid on the environment.

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, the measuring chip assembly 1 according to this embodiment will be described with reference to FIGS. 5 and 6. FIG. 5 and FIG. 6 respectively show a plane shape and a side sectional shape of this measuring chip assembly 1. As shown in the figure, the measurement chip assembly 1 is formed by arranging a plurality of measurement chips 10 in a predetermined number in the vertical and horizontal directions, respectively, and accommodating them in a package 5 so that they can be taken out. In this embodiment, as an example, the package 5 is formed so as to accommodate 8 × 12 = 96 (only 16 in FIG. 5) measuring chips 10.

That is, the package 5 has ribs 5a projecting upward from the bottom plate 5c and defining 96 receiving regions on the bottom plate 5c, and the measuring chip 10 is accommodated in each of these regions. It has become. Here, since the dielectric block 11 constituting the measuring chip 10 of this example has a shape obtained by cutting out a part of the quadrangular pyramid as described above, when the measuring chip 10 is housed in each of the above-mentioned regions, the rib 5a is formed. Comes into contact with the side surface of the dielectric block 11 so that the vertical and horizontal positions of the dielectric block 11 are regulated. Therefore, it is possible to prevent a problem that some of the measurement chips 10 are not aligned in the package 5 and the sample is improperly supplied.

Further, the bottom plate 5c of the package 5 is formed with a through hole 5b for each chip receiving region defined by the rib 5a so that the bottom surface of the measuring chip 10 accommodated therein can be seen.

Next, the operation of taking out the measuring chips 10 one by one from the package 5 of the measuring chip assembly 1 and supplying them to the turntable 20 will be described with reference to FIG. When supplying the measurement chip 10, the package 5 forming the measurement chip assembly 1 is placed at a predetermined position on the turntable 20. And chip automatic supply mechanism
By driving the horizontal moving section 72 and the vertical moving section 74 of 70 in a predetermined sequence, the chip gripping section 75 is moved in the directions of the arrows X and Y, and positioned above the predetermined measuring chip 10 in the package 5. Will be distributed.

At this time, the tip pushing member 76 is interlocked with the tip gripping portion 75 and always maintains a state of facing the tip gripping portion 75. Next, the tip gripper 75 moves downward, and the tip push-up member 76 moves upward accordingly. Then, the chip pushing-up member 76 enters the through hole 5b of the bottom plate 5c of the package 5 and pushes up the bottom surface of the one measurement chip 10 accommodated therein. The measurement chip 10 pushed up projects to a position higher than the other measurement chips 10 accommodated therein, and the projecting measurement chip 10 is gripped by the chip gripper 75.

Then, the lateral moving section 72 and the vertical moving section 74 are driven, so that the tip gripping portion 75 gripping the measuring tip 10 has the through hole 20H of the turntable 20 at the predetermined position.
(See FIG. 2). Next is the chip grip
75 moves down, and the measuring tip 10 being held is fitted and held in the through hole 20H of the turntable 20. When the turntable 20 thus holds the measuring tip 10, the through hole 20
A new through hole that rotates intermittently by the H arrangement angle pitch
20H is in the above-mentioned predetermined position.

Next, after the tip gripping portion 75 is moved up, the above-described operation is repeated, whereby the measuring tips 10 housed in the package 5 are taken out one by one in a predetermined order and supplied to the turntable 20. To be done.

As described above, the tip pushing member 76
The measurement chip 10 is pushed up by means of the above, and the pushed up measurement chip 10 is held by the chip holding portion 75. Even if the measurement chips 10 are accommodated in the package 5 with almost no gap between them, those measurement chips 10 are held. It becomes possible to take out 10 easily and surely.

If the vertical and horizontal arrangement pitches of the measuring chips 10 in the package 5 are matched with the well arrangement pitch in the well plate as described above,
It is also possible to use the existing sample supply means for this type of well plate as it is to supply the sample to the measurement chip 10. As such a sample supply means, for example, a plurality of pipettes integrally connected with their tips facing downward, a dispensing position at which the tips come close to the measurement chip 10 in the package 5, and It is possible to preferably use a device that is configured to move to an upwardly separated standby position and simultaneously dispense a liquid sample to a plurality of measuring chips 10 in one row at the dispensing position.

Next, a second embodiment of the present invention will be described. FIG. 7 shows a planar shape of the measurement chip assembly 101 according to the second embodiment of the present invention.
Is a measurement chip array 110 that constitutes the measurement chip assembly 101.
2 is a perspective view of FIG. As shown in FIG. 8, the measuring chip array 110 is the measuring chip 10 in the first embodiment.
For example, eight measurement chips 10 similar to the above are connected. The measurement chip assembly 101 shown in FIG.
12 of the above-mentioned measuring chip arrays 110 (see FIG. 7).
Then, only two are shown) Package 10 that can be taken out side by side
It is housed in 5.

That is, the package 105 has ribs 105a projecting upward from the bottom plate 105c and defining twelve receiving regions on the bottom plate 105c, and the measuring chip array 110 is accommodated in each of these regions. It is like this. Therefore, also in this example, the package 105 accommodates 8 × 12 = 96 measurement chips 10. The ribs 105a serve to define the vertical and horizontal positions of the measuring chip array 110, that is, the measuring chips 10.

In the bottom plate 105c of the package 105, elongated through holes 105b are formed for each chip row accommodation area defined by the ribs 105a so that the bottom surface of the measurement chip row 110 accommodated thereon can be seen. There is. As a result, also in the present embodiment, it is possible to easily and reliably take out the measurement chip array 110 by pushing up the measurement chip array 110 by the chip pushing member that has entered the through hole 105b from below.

The measuring chip array 110 in which a plurality of measuring chips 10 are connected as described above is arranged in parallel with a plurality of measuring chips as shown in, for example, Japanese Patent Application No. 2001-81967 by the present applicant. It is desirable that the measurement is performed by using a surface plasmon resonance measuring apparatus provided with an optical system for irradiating a plurality of measuring light beams and a plurality of light detecting means provided corresponding to the respective light beams. . Further, the invention is not limited to this, and the measurement chip array 110 is measured by using a surface plasmon resonance measurement device provided with an optical system for irradiating one measurement light beam and one photodetection means provided corresponding thereto. The measurement using each measurement chip 10 may be sequentially performed by sequentially sending the chips 10 in the arrangement direction.

Since the measurement chip assembly 101 described above is formed by arranging a plurality of measurement chips 10 in a predetermined number in the vertical and horizontal directions and removably housed in the package 105, this measurement chip assembly 101 is arranged. According to 101, it becomes possible to easily transport a plurality of measurement chips 10 together and to simultaneously supply samples to them. this is,
The same applies to the measurement chip assembly 1 according to the first embodiment.

Such a measuring chip assembly according to the present invention may be conveyed one by one, but it is also possible to handle a plurality of them. FIG. 9 shows an example of such a form. Here, the measurement chip assembly 1 according to the first embodiment is, for example, 5
Individually stacked, they are housed in the transport container 200 and transported.

The carrying container 200 is made of, for example, a thick transparent synthetic resin sheet, and the folded-back portion 201 is fixed by a magic fastener (registered trademark) 202.
It is assembled in a box shape from the unfolded state. Further, a handle 203 for carrying is attached to the upper part thereof. The transport container 200 having such a structure facilitates storage and removal by storing the plurality of measurement chip assemblies 1 in the container and unfolding the measurement chip assembly 1 from the container. There is an advantage that you can.

The measuring chip assembly 1 in an integrated state
The container for collectively transporting the above is not limited to the transport container 200 described above, and it is needless to say that various known containers made of other materials and structures can be applied.

Next, another measuring apparatus to which the measuring chip assembly of the present invention can be applied will be described with reference to FIG.
FIG. 10 shows a side view of a leaky mode measuring device using the measuring chip 700. This leaky mode measuring device basically has the same configuration as the surface plasmon resonance measuring device shown in FIG. On the other hand, the measuring chip 700 used here has a cladding layer 701 formed on one surface (the upper surface in the drawing) of the dielectric block 11, and an optical waveguide layer 702 further formed thereon.

The dielectric block 11 is formed into a substantially rectangular columnar shape using, for example, the transparent resin described above. On the other hand, the clad layer 701 is formed into a thin film using a dielectric material having a lower refractive index than the dielectric block 11 or a metal such as gold. The optical waveguide layer 702 is also formed in a thin film shape by using a dielectric material having a higher refractive index than the cladding layer 701, for example, PMMA. The film thickness of the clad layer 701 is, for example, 36.5 nm when it is formed from a gold thin film, and the film thickness of the optical waveguide layer 702 is approximately 700 nm when it is formed from PMMA, for example.

In the leaky mode measuring device having the above structure,
Dielectric block the light beam 30 emitted from the laser light source 31
When the light beam 30 is incident on the clad layer 701 through 11 at an angle of total reflection or more, the light beam 30 is totally reflected at the interface 11 a between the dielectric block 11 and the clad layer 701, but is transmitted through the clad layer 701. Light with a specific wave number that has entered the optical waveguide layer 702 at a specific incident angle propagates through the optical waveguide layer 702 in a guided mode. When the guided mode is excited in this way, most of the incident light is taken into the optical waveguide layer 702, so that the total reflection attenuation occurs in which the intensity of the light totally reflected at the interface 11a sharply decreases.

Since the wave number of the guided light in the optical waveguide layer 702 depends on the refractive index of the sample 15 on the optical waveguide layer 702, by knowing the specific incident angle at which attenuation of total reflection occurs,
The refractive index of the sample 15 and the characteristics of the sample 15 related thereto can be analyzed. The signal processing unit 61 quantitatively analyzes the specific substance in the sample 15 based on the above principle, and the analysis result is displayed on the display unit (not shown).

The measuring chip 700 used in this leaky mode measuring apparatus is also housed in a package in the form shown in FIG. 5 or the form shown in FIG. 7, for example.
A measuring chip assembly can be constructed. Even in such a case, the same effect as described above can be obtained by using the measurement chip assembly.

[Brief description of drawings]

FIG. 1 is an overall view of a surface plasmon resonance measuring apparatus using a measuring chip assembly according to the present invention.

FIG. 2 is a partially cutaway side view showing a main part of the surface plasmon resonance measurement apparatus of FIG.

FIG. 3 is a perspective view showing a measuring chip that constitutes the measuring chip assembly.

FIG. 4 is a graph showing a schematic relationship between a light beam incident angle and a light intensity detected by a photodetector in the surface plasmon resonance measuring apparatus.

FIG. 5 is a plan view showing a measuring chip assembly according to the first embodiment of the present invention.

6 is a side sectional view of the measuring chip assembly of FIG.

FIG. 7 is a plan view showing a measuring chip assembly according to a second embodiment of the present invention.

FIG. 8 is a perspective view showing a measuring chip row forming the measuring chip assembly of FIG.

FIG. 9 is a perspective view showing a container for accumulating and transporting a measuring chip assembly according to the present invention.

FIG. 10 is a partially cutaway side view showing a main part of a leaky mode measuring apparatus using a measuring chip assembly according to the present invention.

[Explanation of symbols]

1,101 Measuring chip assembly 5,105 packages Ribs for 5a and 105a packages 5b, 105b Package through hole 5c, 105c package bottom plate 10 Surface plasmon resonance measurement chip 11 Dielectric block 11a One side of dielectric block 11b Dielectric block light incident surface 11c Light exit surface of dielectric block 12 Metal film 13 Sample holding frame 14 Sensing medium 15 samples 70 chip automatic supply mechanism 71 Horizontal guide rail 72 Lateral movement part 73 Vertical guide rail 74 Vertical movement part 75 Chip grip 76 Tip pushing member 700 Measuring chip for leak mode measuring device 701 Clad layer 702 Optical waveguide layer

Front page continuation (51) Int.Cl. ⁷ Identification code FI theme code (reference) G01N 35/04 G01N 35/04 GF term (reference) 2G057 AA02 AB04 AB07 AC01 BA01 BB01 BB06 BC07 HA04 2G058 CD04 CD23 CF12 GA02 2G059 AA01 BB04 BB12 CC16 DD12 DD13 EE02 EE05 FF04 GG01 GG04 JJ11 JJ12 JJ17 JJ19 JJ25 KK03 KK04 MM01 MM03 MM09 MM11 PP04

Claims (8)

[Claims] 1. A dielectric block, a thin film layer formed on one surface of the dielectric block and brought into contact with a sample, a light source for generating a light beam, and the light beam for the dielectric block. At the interface between the dielectric block and the thin film layer, the total reflection condition is satisfied, and the optical system is made to enter so as to include various incident angle components, and the intensity of the light beam totally reflected at the interface is measured to attenuate the total reflection. A measuring chip used in a measuring device utilizing attenuation of total reflection, comprising a light detecting means for detecting a state, wherein the dielectric block is an incident surface of the light beam, an emitting surface facing the incident surface. And a plurality of measuring chips formed in one block including all of the one surface on which the thin film layer is formed and in which the thin film layer is integrated with this dielectric block in the vertical and horizontal directions. Each side-by-side by a predetermined number,
A measuring chip assembly housed in a package so that it can be taken out. 2. A dielectric block, a thin film layer made of a metal film formed on one surface of the dielectric block and brought into contact with a sample, a light source for generating a light beam, and the light beam to the dielectric block. On the other hand, an optical system that makes the total reflection condition at the interface between the dielectric block and the metal film and that includes various incident angle components, and the intensity of the light beam totally reflected at the interface are measured. A measuring chip for use in a measuring device utilizing attenuated total reflection, comprising: a light detecting means for detecting a state of attenuated total reflection due to surface plasmon resonance, wherein the dielectric block is the incidence of the light beam. Surface, an exit surface facing the entrance surface, and one surface on which the thin film layer is formed, are formed as one block, and the thin film layer is integrated with the dielectric block. Comprising Te measuring chip is more vertical, respectively side by side by a predetermined number in the horizontal direction,
A measuring chip assembly housed in a package so that it can be taken out. 3. A thin film layer comprising a dielectric block, a clad layer formed on one surface of the dielectric block, and an optical waveguide layer formed on the clad layer and brought into contact with a sample, and a light source for generating a light beam. An optical system that causes the light beam to enter the dielectric block such that total reflection conditions are present at the interface between the dielectric block and the cladding layer and that various incident angle components are included; and A measuring device utilizing attenuated total reflection, comprising: a light detecting means for measuring the intensity of a totally reflected light beam to detect a state of attenuation of total reflection due to excitation of a guided mode in the optical waveguide layer. A measuring chip used, wherein the dielectric block is one block including all of an incident surface of the light beam, an emission surface facing the incident surface, and one surface on which the thin film layer is formed. Is to form, this dielectric block wherein the thin film layer are integrated measuring chip multiple, longitudinal, side by side respectively in a horizontal direction by a predetermined number,
A measuring chip assembly housed in a package so that it can be taken out. 4. The measurement chip assembly according to claim 1, wherein each of the measurement chips is independently housed in the package. 5. A plurality of the measurement chips are connected in one of the vertical and horizontal directions to form a chip row, and the plurality of chip rows are arranged in the other of the vertical and horizontal directions and accommodated in the package. The measuring chip assembly according to any one of claims 1 to 3, wherein: 6. The dielectric block is formed by cutting out a part of a substantially polygonal pyramid, and the package has a rib that abuts a side surface of the dielectric block and defines a position of the dielectric block. The measuring chip assembly according to any one of claims 1 to 5, wherein: 7. The measuring chip according to claim 1, wherein the bottom plate of the package is formed with a through hole through which the bottom surface of the measuring chip accommodated therein can be seen. Aggregation. 8. A measuring chip take-out device for taking out a measuring chip from the measuring chip assembly according to claim 7,
A device for taking out a measurement chip, comprising a member that enters into the package through a through hole formed in a bottom plate of the package and pushes up a bottom surface of the measurement chip.