JP2003194712A - Apparatus and chip for measurement making use of attenuated total reflection - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To simply set a measuring chip used for a measuring apparatus making use of attenuated total reflection to a state that a prescribed incident face and a prescribed outgoing face in a dielectric block are situated in correct positions with reference to the measuring apparatus. <P>SOLUTION: In the measuring chip 10, a dielectric block 11 is formed as one block which contains the incident face 11b for a measuring light beam, the outgoing face 11c, and one face on which a thin-film layer 12 is formed. The surface roughness of a face 11p and a face 11q which are situated between the incident face 11b and the outgoing face 11c in the dielectric block 11 is set to be larger than the surface roughness of the incident face 11b and the outgoing face 11c. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

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

The present invention also relates to a measuring chip used in a measuring device utilizing such kind of attenuated total reflection.

[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).

As described above, the measuring chip has 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 light beam. For the dielectric block,
The total reflection condition is measured at the interface between the dielectric block and the thin film layer, and an optical system that allows light to be incident so that various incident angle components are included, and the total reflection attenuation at the interface are measured. In a measuring chip used in a measuring device utilizing attenuated total reflection, the dielectric block includes an incident surface, an emitting surface, and the thin film layer of the light beam. It is formed as one block including all of the one surface to be formed, 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, as the above-mentioned dielectric block, generally, a shape obtained by cutting out a part of a substantially square pyramid or a shape such as a substantially square pole (that is, parallel to a surface on which a thin film layer is formed) is used. The shape of the cross section is a quadrangle)
A resin obtained by injection molding a resin is preferably used. In the dielectric block having such a shape, two surfaces of the four side surfaces facing each other are the incident surface and the emission surface of the light beam, and it is desired that those surfaces have extremely high flatness. That is, if the flatness of the entrance surface and the exit surface is low, the light beam passing therethrough undergoes irregular reflection and irregular incidence, which lowers the amount of detected light and lowers the S / N of the measurement data. .

Considering the usability of the measuring chip, it is desirable that all four surfaces have high flatness. That is, with such a configuration, even if the dielectric block is set in the measuring device so that any two of the four surfaces become the entrance surface and the exit surface, the flatness of the entrance surface and the exit surface is Because it will be expensive.

However, when a resin block is injection-molded to form a dielectric block having the above-described shape, the two blocks face each other due to the flow state of the molten resin in the mold.
Although the surface has high flatness, the flatness is inferior to the other two surfaces due to so-called resin sink marks,
The situation is likely to occur. Therefore, when using a measuring chip composed of a dielectric block obtained by injection-molding a resin in this way, the user visually observes the dielectric block and confirms that the flatness of the flat surface is such that sink marks do not occur. It is necessary to set the measuring chip in the measuring device so that the high surface becomes the incident surface and the outgoing surface. It takes a great deal of labor and time to perform such observations for all the measurement chips used, which in turn increases the cost of measurement.

Accordingly, the present invention provides a measuring chip that can be easily set in a state in which a predetermined incident surface and an emitting surface of a dielectric block are in correct positions, for a measuring device utilizing attenuation of total internal reflection. To aim.

The present invention also provides such a measuring chip,
It is an object of the present invention to provide a measuring device using attenuated total reflection that can be easily set in a state where a predetermined incident surface and an emitting surface of a dielectric block are in correct positions.

[0026]

One measuring chip according to the present invention includes a dielectric block as described above, a thin film layer formed on one surface of the dielectric block and brought into contact with a sample, and a light beam generating device. A light source for causing the light beam to enter the dielectric block such that total reflection conditions are satisfied at an interface between the dielectric block and the thin film layer and various incident angle components are included. A measuring chip for use in a measuring apparatus utilizing attenuated total reflection, comprising: a photodetecting means for measuring the intensity of a light beam totally reflected at an interface to detect a state of attenuation of total reflection. A block is formed as a block including 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, and the block is formed in front of the dielectric block. In a measuring chip in which thin film layers are integrated, surface roughness of a surface of the dielectric block between the incident surface and the emission surface is larger than surface roughness of the incident surface and the emission surface. To do.

Further, another measuring chip according to the present invention is formed as a measuring chip for the above-mentioned surface plasmon resonance measurement, namely, a dielectric block and
A thin film layer made of a metal film formed on one surface of the dielectric block and brought into contact with the sample, a light source for generating a light beam, and the light beam to the dielectric block,
The surface plasmon is obtained by measuring the intensity of the light beam totally reflected at the interface and an optical system that makes the interface such that the total reflection condition exists at the interface between the dielectric block and the metal film and includes various incident angle components. A measuring chip for use in a measuring device utilizing attenuated total reflection, comprising: a light detection means for detecting a state of attenuation of total reflection due to resonance, wherein the dielectric block is an incident surface of the light beam, In a measuring chip formed as one block including all of an exit surface facing an entrance surface and one surface on which the thin film layer is formed, the dielectric block is integrated with the thin film layer. The surface roughness of the surface between the incident surface and the emission surface is larger than the surface roughness of the incident surface and the emission surface.

Still another measuring chip according to the present invention is the above-mentioned measuring chip for leak mode measurement, that is, the dielectric block, the clad layer formed on one surface of the dielectric block, and the dielectric block on the dielectric block. A thin film layer formed of the optical waveguide layer that is brought into contact with the sample,
A light source that generates a light beam, and an optical device that causes the light beam to enter the dielectric block such that total reflection conditions are satisfied at the interface between the dielectric block and the clad layer and that various incident angle components are included. Attenuation of total reflection, comprising: a system; and a light detecting means for measuring the intensity of a light beam totally reflected at the interface to detect a state of attenuation of total reflection due to excitation of a guided mode in the optical waveguide layer. 1. A measuring chip used in a measuring device utilizing, wherein the dielectric block is a 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. In the measurement chip in which the thin film layer is integrated with this dielectric block, the surface roughness of the surface between the entrance surface and the exit surface of the dielectric block is It is characterized in that greater than the surface roughness of the incident surface and the exit surface.

In each measuring chip according to the present invention, when the wavelength of the light beam is λ, the surface roughness of the incident surface and the emission surface of the light beam of the dielectric block is λ / 2.
It is desirable to be less than. Here, the surface roughness is J
It shall be specified by the rms surface roughness Rq defined by IS B 0090-8.

In each measuring chip according to the present invention,
It is desirable that the dielectric block has a shape obtained by cutting out a part of a substantially square pyramid or a substantially square pillar shape. When the dielectric block has such a shape, it is desirable that the shape of the cross section parallel to the one surface on which the thin film layer of the dielectric block is formed is a quadrangle having different vertical and horizontal lengths.

On the other hand, in the measuring apparatus utilizing the attenuation of total reflection according to the present invention, the shape of the cross section parallel to the one surface on which the thin film layer of the dielectric block is formed is a quadrangle whose vertical and horizontal lengths are different from each other. Using the above-mentioned measuring chip, 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 dielectric beam for the light beam. For the block, an optical system which makes the total reflection condition at the interface between the dielectric block and the thin film layer and includes various incident angle components, and the intensity of the light beam totally reflected at the interface are measured. Then, in a measuring device utilizing attenuated total reflection, which comprises a light detection means for detecting the state of attenuated total reflection, the portion for receiving the measuring chip is the four sides having different vertical and horizontal lengths. The cross-section is characterized in that it is shaped to match the viewing said quadrilateral cross-section when the measuring chip is arranged in a state where a predetermined direction.

[0032]

In the measuring chip according to the present invention, the surface roughness of the surface of the dielectric block between the incident surface and the emission surface of the light beam is larger than the surface roughness of the incident surface and the emission surface. Therefore, at a glance, it becomes possible to easily identify which surface is the incident surface and the exit surface and which surface is the other surface. That is, it is visually recognized that the incident surface and the exit surface have high transparency and the other surfaces have low transparency. Therefore, when the user sets the measuring chip on the measuring device, the measuring chip can be easily set in a state where the incident surface and the emitting surface are in the correct positions.

Particularly, in each measuring chip according to the present invention, when the wavelength of the light beam is λ, the surface roughness Rq of the incident surface and the emission surface of the light beam of the dielectric block is λ / 2.
When it is less than the above value, the interference of the light beams is effectively prevented by the effect of the unevenness of those surfaces, and the total reflected light detection signal having a high S / N can be obtained.

When the dielectric block has a shape obtained by cutting out a part of an approximately quadrangular pyramid or an approximately quadrangular prism, two planes facing each other have high flatness as described above, and different from them. Since it is easy for the two surfaces to have poor flatness, applying the present invention in such a case ensures that the two surfaces having poor flatness are used as the entrance surface and the exit surface. Since it can be prevented, it is particularly preferable.

When the dielectric block has such a shape, the shape of the cross section parallel to the one surface of the dielectric block on which the thin film layer is formed may be a quadrangle whose vertical and horizontal lengths are different from each other. For example, by devising the shape of the portion that receives the measuring chip of the measuring device, it is possible to completely prevent the dielectric block from being received in this portion in the wrong orientation.

Therefore, in the measuring apparatus using attenuation of total reflection according to the present invention, the portion receiving the measuring chip has a quadrilateral cross section in which the lengths of the dielectric block are different from each other in the predetermined direction. Since the shape is configured to match the cross section of the quadrangle only when the measuring tip is placed in the state, it is not possible to set the measuring tip in a direction other than this state, that is, a direction rotated by 90 ° from that state, for example. It's impossible. Therefore, according to the measuring apparatus using the attenuated total reflection according to the present invention, it is possible to completely prevent the measuring chip from being set in the wrong direction, and the reliability of the measurement can be sufficiently improved.

[0037]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 3 shows a perspective shape of the surface plasmon resonance measurement chip according to the first embodiment of the present invention. 1 shows the overall shape of a surface plasmon resonance measuring apparatus using this measuring chip, and FIG. 2 shows the side surface shape of the main part of this apparatus. 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 measuring light beam (laser beam) 30. , 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 the processing described below, and an automatic sample 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 substantially square pyramid is cut off, and gold, for example, formed on the upper surface of the dielectric block 11. It is composed of a metal film 12 made of silver, copper, aluminum or the like, and a cylindrical sample holding frame 13 that defines a space closed on the side of the metal film 12. The dielectric block 11 has one surface 11a on which the metal film 12 is formed.
1 (including a surface forming an interface described later), a surface 11b on which the light beam 30 enters, and a surface 11c on which the light beam 30 exits 1
It is formed as one block. 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, and amorphous polyolefin. 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" is shown in the drawing) 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 a 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 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 automatic sample supply mechanism 70 includes, for example, a pipette 71 for sucking and holding a predetermined amount of a liquid sample, and this pipette 71.
And a means 72 for displacing the sample, and the sample pipette 71 is sucked and held from the sample container 73 set at a predetermined position, and the sample is held in the sample holding frame 13 of the measurement chip 10 at the predetermined stop position. The sample is supplied dropwise.

The sample analysis by the surface plasmon resonance measuring apparatus having the above-mentioned structure will be described below. During sample analysis, the turntable 20 has the support driving means 50 as described above.
It is rotated intermittently by. And turntable
When the sample 20 is stopped, the sample holding frame 13 of the measuring chip 10 which is stationary at a predetermined position is provided with the sample 15 by the sample automatic supply mechanism 70.
Is supplied.

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 such that the light beam 30 is incident on 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 a 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.

The measuring chip 10 does not need to optically couple the dielectric block 11 with another dielectric block through the index matching liquid, which 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 .

The dielectric block 11 can be formed not only by injection molding of a resin, but also by a method of further polishing after injection molding, a method of cutting out from a large resin block and then polishing. For example, when the dielectric block 11 is manufactured by injection molding of resin, four side surfaces of the dielectric block 11, that is, the light incident surface 11
b and the light emitting surface 11c, and the side surface 11 between them.
For p and 11q, the state of the molding surface of the injection molding die is transferred as it is and molded. In this example, the surfaces forming the light incident surface 11b and the light emitting surface 11c have a surface roughness R
q (rms surface roughness defined by JIS B 0090-8. The same applies hereinafter) is less than λ / 2 (λ is the wavelength of the light beam 30).
On the other hand, the surfaces on which the side surface 11p and the side surface 11q are molded have a surface roughness Rq extremely larger than λ / 2.

Therefore, the injection-molded dielectric block 11 is used.
(See FIG. 3), the light incident surface 11b and the light emitting surface 11
c is a surface having a surface roughness Rq of less than λ / 2 and high transparency, while the side surfaces 11p and 11q between them have a surface roughness Rq of much greater than λ / 2 and a low transparency, such as a ground glass. Will be things. Due to the difference in transparency, the user can easily distinguish the light incident surface 11b and the light emitting surface 11c from the side surfaces 11p and 11q. Therefore, when the user sets the measuring chip 10 including the dielectric block 11 in the through hole 20H (see FIG. 2) of the turntable 20, the light incident surface 11b and the light emitting surface
It is possible to easily set 11c at a correct position, that is, a position where the light beam 30 enters and exits.

Specifically, in this embodiment, as an example, λ
= 980 nm, the light incident surface 11b and the light emitting surface 11c
Surface roughness Rq of 0.272 μm less than λ / 2, side surface 11
The surface roughness Rq of p and 11q is 3.306 μm, which is sufficiently larger than λ / 2.

In the present embodiment, as described above, the light incident surface 11
Since b and the light emitting surface 11c are surfaces having a surface roughness Rq of less than λ / 2, it is possible to effectively prevent the light beam 30 from interfering with each other due to the effect of the unevenness of the surfaces 11b and 11c. A light amount detection signal S having a high / N can be obtained.

In addition, when the dielectric block 11 having a shape in which a part of the approximately quadrangular pyramid is cut out is injection-molded, the two surfaces facing each other have high flatness, and the other two surfaces are different from each other. Is less likely to have poor flatness. However, by applying the present invention to the measuring chip 10 including the dielectric block 11 having such a shape, two surfaces having poor flatness are a light incident surface and a light receiving surface. It can be reliably prevented from being used as the emitting surface.

As shown in FIG. 5, the dielectric block 11 having a shape obtained by cutting out a part of an approximately quadrangular pyramid has a cross-sectional shape parallel to one surface 11a (see FIG. 2) on which a thin film layer is formed.
It may be a rectangle whose vertical and horizontal lengths are different from each other. At the same time, if the shape of the through hole 20H of the turntable 20 (see also FIG. 2) is rectangular according to the cross-sectional shape of the dielectric block 11, the dielectric block 11 is correct as shown in FIG. It only goes through when it is oriented 20
When the dielectric block 11 is fitted and held in H and is placed in the wrong direction as shown in FIG.
Since it is completely impossible to fit the dielectric block 11 to the turntable 20, it is completely prevented that the dielectric block 11 is supported by the turntable 20 in the wrong direction.

Further, when the dielectric block is in the shape of a substantially quadrangular prism, the cross-sectional shape may be the above-mentioned shape, and in that case, the same operation and effect as above can be obtained.

Next, another embodiment of the present invention will be described with reference to FIG. FIG. 6 shows a side view of a leaky mode measuring apparatus using the measuring chip 700 according to the second embodiment of the present invention. 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 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 above-mentioned 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).

Also in the leaky mode measuring apparatus of this embodiment, the dielectric block 11 constituting the measuring chip 700 is
The light incident surface 11b and the light emitting surface 11c are formed so that the surface roughness is relatively small, and the surface between them is relatively large. As a result, also in this embodiment, it is possible to easily discriminate between the light incident surface 11b and the light emitting surface 11c, and it is possible to reliably prevent the measurement chip 700 from being set on the turntable 20 in the wrong direction. To be done.

The present invention is not limited to the case where the dielectric block is formed into a shape obtained by cutting out a part of the approximate quadrangular pyramid or the approximate quadrangular prism, but is also applicable to the case where the dielectric block is formed into, for example, an approximate hexagonal prism. Can also be applied in the same manner, and in that case, the desired effect can be similarly obtained.

[Brief description of drawings]

FIG. 1 is an overall view of a surface plasmon resonance measuring apparatus using a measuring chip 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 resonance measurement apparatus of FIG.

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

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 schematic view showing another example of the shape of the measuring chip of the present invention.

FIG. 6 is a partially cutaway side view showing a leaky mode measuring apparatus using a measuring chip according to a second embodiment of the present invention.

[Explanation of symbols]

10 Surface Plasmon Resonance Measurement Chip 11 Dielectric Block 11a Dielectric Block One Surface 11b Dielectric Block Light Incident Surface 11c Dielectric Block Light Emitting Surface 11p, 11q Sides Other than Dielectric Block Light In and Out Surface 12 Metal Film 13 Specimen holding frame 14 Sensing medium 15 Specimen 700 Leakage mode measuring device measuring tip 701 Cladding layer 702 Optical waveguide layer

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 2G057 AA02 AB04 AB07 AC01 BA01                       BB01 BB06 HA04                 2G058 AA09 CC17 CD04 CF12 EA02                       ED03 GA02                 2G059 AA01 AA02 DD12 DD13 EE02                       GG01 JJ11 JJ12 KK01 MM01                       MM14 PP04

Claims (5)

[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 reduce the total reflection attenuation. 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 measuring chip which is formed as 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 the dielectric block. A measuring chip, wherein the surface roughness of a surface of the lock between the incident surface and the emission surface is larger than the surface roughness of the incident surface and the emission surface. 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. In the measurement chip comprising Te, measurement tip the incident surface and the surface roughness of the surface lying between the exit surface of the dielectric block, being larger than the surface roughness of the incident surface and the exit surface. 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. In the measuring chip formed by integrating the thin film layer with the dielectric block, the surface roughness of the surface between the entrance surface and the exit surface of the dielectric block is A measuring tip characterized by being larger than the surface roughness of the surface. 4. The dielectric block has a shape obtained by cutting out a part of an approximately quadrangular pyramid or an approximately quadrangular prism, and a shape of a cross section parallel to one surface of the dielectric block on which the thin film layer is formed. Is a quadrangle whose vertical and horizontal lengths are different from each other, and the measuring chip according to any one of claims 1 to 3. 5. 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 reduce the total reflection attenuation. A measuring device using attenuated total reflection, comprising: a light detecting means for detecting a state, wherein the measuring chip according to claim 4 is used, and a portion for receiving the measuring chip has the vertical and horizontal directions. Attenuation utilizing total reflection is characterized in that the quadrilateral has a shape matching the quadrangular cross section only when the measuring tip is placed in a state where the quadrilateral cross sections having different lengths are in a predetermined direction. measuring device.