JP4939108B2 - Microchip - Google Patents

Description

  The present invention relates to a microchip.

  In recent years, Labs that separate, react, mix, measure, and detect biological materials such as enzymes, proteins, viruses, and cells on substrates of several millimeters and several centimeters in the fields of medicine, food, drug discovery, etc. A technology called “on a Chip” has attracted attention in recent years. Chips used in Lab on a Chip are generally called microchips. For example, clinical analysis chips, environmental analysis chips, gene analysis chips (DNA chips), protein analysis chips (proteome chips), sugar chain chips, chromatographs There are chips, cell analysis chips, pharmaceutical screening chips and the like.

  One of the sample quantification methods using a microchip is a quantification method using a light transmission amount. In such a microchip, in addition to the processing unit for performing the above-described separation, reaction, mixing, and measurement, there is a cuvette unit having an end portion that emits light and an end portion that emits transmitted light. Is provided. Then, the microchip is installed in a measuring device that measures the amount of transmitted light, and the transmitted light transmitted through the cuvette portion is measured to quantify the sample. The measuring device is provided with a slit for limiting the transmitted light passing through the cuvette part, and the microchip is installed by aligning the cuvette part and the slit. However, if the slit for limiting the transmitted light is provided on the measuring device side in this way, if the microchip and the measuring device cannot be accurately aligned, the positional deviation between the cuvette portion and the slit occurs. . Therefore, the transmitted light passing through the cuvette portion cannot be accurately controlled, that is, the transmitted light cannot be accurately restricted, and the sample cannot be accurately quantified.

Therefore, Patent Document 1 discloses a configuration in which a slit is provided on the microchip side to prevent positional displacement between the cuvette part and the slit and the transmitted light passing through the cuvette part is accurately controlled. The slit of patent document 1 is formed by covering parts other than a cuvette part with a metal chromium film.
JP 2004-53345 A

  However, in Patent Document 1, a metal chromium film is formed on a quartz glass plate by sputtering, and a slit is formed by removing a portion of the metal chromium film corresponding to the cuvette portion by etching. Thus, in the method of Patent Document 1, it is necessary to go through steps such as sputtering and etching, and the manufacturing process is complicated. In addition, since it is necessary to use an expensive device such as a vacuum device for these steps, it is difficult to reduce the cost of the microchip.

Furthermore, it is difficult to apply such an etching process to a plus chip substrate generally used in a microchip. This is because in order to pattern the photoresist used in the etching process, a chemical treatment process using a heat treatment or an alkaline solution is required, and deformation and cracks occur when applied to a plastic substrate.
Moreover, in patent document 1, since the metal chromium film | membrane which comprises a slit, and the quartz glass substrate which makes a cover part differ, when it bonds together by methods, such as welding, the intensity | strength of a microchip will become weak, In the first place, bonding is difficult. Therefore, it is necessary to make the same material by sputtering quartz glass on the metal chromium film and to improve the adhesion between the two substrates. Such a separate film formation further increases the manufacturing cost.

  Accordingly, an object of the present invention is to provide a microchip capable of accurately controlling the transmitted light passing through the cuvette portion and simplifying the manufacturing process and reducing the manufacturing cost.

  In order to solve the above problems, the first invention of the present application is formed of a detection path formed inside the substrate and into which a sample to be quantified is introduced, and a substrate at one end of the detection path, and light is incident on the detection path. And an emission end that emits light that has passed through the detection path to the outside of the substrate. The emission end of the light that is emitted from the detection path In order to limit the area, at least one of a notch portion of the substrate outer wall corresponding to one end of the detection path of the emission end portion and a chamfered portion of the detection path inner wall of the incident end portion is formed. I will provide a.

  The amount of transmitted light should depend on the nature of the sample introduced into the detection path, but the amount of transmitted light varies depending on the exit area from which it is emitted. In the present invention, the above-described configuration limits the emission area of the light emitted from the emission end to a desired area. This eliminates an error in the amount of transmitted light due to the difference in the light emission area, and allows the sample to be accurately quantified. In addition, since the incident end and the emission end that limit the light emission area are formed from the substrate integrally with the detection path, the notch or the incident end of the emission end that restricts the light emission area is formed. There is no positional deviation between the chamfered portion and the optical axis of the light passing through the detection path. This also makes it possible to accurately quantify the sample by limiting the emission area of the transmitted light to a desired area. As described above, according to the configuration of the present invention, even a very small amount of sample can be accurately quantified with less error.

The notch at the exit end and / or the chamfered portion at the entrance end that limit the light exit area are formed by notching the same substrate as the detection path, and therefore in the same process as the detection path using injection molding. Can be formed at once. Therefore, it is possible to prevent the displacement of the detection path from the cut-out portion of the emission end portion and / or the chamfered portion of the incident end portion that limits the light emission area from the manufacturing surface.
Also, since the formation of the cut-out portion of the exit end and the chamfered portion of the entrance end and the formation of the detection path are the same process, a special for forming the cut-out portion of the exit end and the chamfer of the entrance end. An unnecessary process is unnecessary, and the manufacturing cost can be reduced. Furthermore, the manufacturing of microchips by injection molding does not require an etching process such as heat treatment for patterning a photoresist, wet etching using an alkaline solution, or dry etching. Therefore, the cuvette portion can be formed even with a material having a relatively low resistance to etching. For example, application to a glass substrate other than a glass substrate can be considered. In addition, since injection molding is less expensive than the etching process as described above, a microchip can be manufactured at low cost.

According to a second invention of the present application, in the first invention, the notched portion of the emission end portion and / or the chamfered portion of the incident end portion selectively emits light that has passed through a central portion in the cross-sectional direction of the detection path. Thus, a microchip for controlling the light emission direction is provided.
Bubbles may be generated on the inner wall of the detection path when a sample is introduced into the detection path. Due to the bubbles adhering to the inner wall of the detection path, the light passing near the inner wall of the detection path is scattered, and there is a possibility that the amount of transmission of the light detected from the emission end will vary. The cutout portion of the exit end and the chamfered portion of the entrance end of the present invention prevent light that has been affected by passing through the vicinity of the inner wall of the detection path and being diffusely reflected by bubbles from being emitted from the exit end. Only the light that has passed through the central portion of the detection path is emitted. Thereby, the fluctuation | variation of the permeation | transmission amount of the light resulting from the bubble adhering to the inner wall of a detection path can be eliminated, and a sample can be quantified correctly.

  According to a third aspect of the present invention, in the first aspect of the present invention, a cutout portion is formed in the outer wall of the substrate corresponding to one end of the detection path, and the cutout portion of the emission end portion is the detection end portion. A recess is formed that includes a bottom surface substantially perpendicular to the optical axis of light passing through the path and a side surface including at least one inclined surface surrounding the bottom surface, and the recess has an opening toward the bottom surface. Provided is a microchip formed so as to be narrowed.

  The fact that the opening of the recessed portion becomes narrower toward the bottom surface on the outer wall of the emitting end portion means that the opening of the recessed portion is formed so as to gradually spread in the light emitting direction. That is, the inclined surface of the recess that forms the cutout portion of the emission end is inclined so as to be away from the optical axis with respect to the bottom surface of the recess as it goes in the light emission direction. Therefore, of the light that has passed through the detection path, the light that is incident on the inclined surface of the cutout portion of the emission end is reflected by the inclined surface and is not emitted outside the substrate from the emission end. On the other hand, of the light that has passed through the detection path, the light incident on the bottom surface that is substantially perpendicular to the optical axis passes through the bottom surface of the cutout portion of the emission end and is emitted to the outside of the substrate. Therefore, the emission area of the light emitted from the emission end to the outside of the substrate can be limited to the area of the bottom surface of the recess that forms the notch of the emission end. This eliminates an error in the amount of transmitted light due to the difference in the light emission area, and allows the sample to be accurately quantified.

  In addition, light that has been affected by being reflected near the inner wall of the detection path and being diffusely reflected from the bubble is reflected by the inclined surface of the cutout portion of the exit end, so that fluctuations in the amount of transmitted light due to the bubble are reduced. Can be eliminated. Furthermore, since the inclined surface of the notch at the exit end is inclined away from the optical axis in the direction of light emission, the light incident on the inclined surface is reflected outward from the detection path and detected. Do not head inside the road. For this reason, it is possible to prevent the light reflected by the inclined surface from affecting the light incident on the bottom surface of the concave portion and changing the light transmission amount.

In a fourth invention of the present application, in the third invention, the angle θ ₁ (θ ₁ <90 °) formed by the bottom surface of the notch at the exit end and the inclined surface is a critical angle represented by the following formula (1): A microchip larger than θ _x is provided.

ここで、ｎ₀は基板が載置されている雰囲気の屈折率、
ｎ₁は前記基板の屈折率。
出射端部の切り欠き部の底面と傾斜面とがなす角θ₁が関係式（１）を満たす臨界角θ_xよりも大きい場合、出射端部の切り欠き部の傾斜面に入射された光は全反射される。よって、出射端部の切り欠き部がこのような傾斜面を有する場合には、検出路を通過した光のうち出射端部の切り欠き部の傾斜面に入射された光は検出路の外側に全反射され、切り欠き部の底面に入射された光は出射端部から基板外部に出射される。このようにして、出射端部から出射される光の出射面積を所定面積に制限することで、試料を正確に定量することができる。

Where n ₀ is the refractive index of the atmosphere in which the substrate is placed,
n ₁ is the refractive index of the substrate.
When the angle θ ₁ formed by the bottom surface of the notch at the exit end and the inclined surface is larger than the critical angle θ _x satisfying the relational expression (1), the light incident on the inclined surface of the notch at the exit end Is totally reflected. Therefore, when the notch at the exit end has such an inclined surface, the light incident on the inclined surface of the notch at the exit end of the light that has passed through the detection path is outside the detection path. The light that is totally reflected and incident on the bottom surface of the notch is emitted from the emission end to the outside of the substrate. In this way, the sample can be accurately quantified by limiting the emission area of the light emitted from the emission end to a predetermined area.

  According to a fifth aspect of the present invention, in the third aspect of the present invention, a chamfered portion is further formed on the inner wall of the detection path at the emission end, and the chamfered portion of the emission end is a light beam that passes through the detection path. Forming a recess composed of a bottom surface substantially perpendicular to the axis and a side surface including at least one inclined surface surrounding the bottom surface, the recess being formed such that the opening of the recess becomes narrower toward the bottom surface. Provide a microchip.

The fact that the opening of the concave portion narrows toward the bottom surface on the inner wall of the detection path on the emission end side means that the opening of the concave portion gradually narrows along the light emission direction. In other words, the inclined surface of the recess that forms the chamfered portion of the emission end portion is inclined so as to approach the optical axis with respect to the bottom surface of the recess as it goes in the light emission direction. Therefore, of the light that has passed through the detection path, the light incident on the inclined surface of the chamfered portion of the exit end is refracted away from the optical axis, travels through the exit end, and is incident on the inclined surface of the notch. The Eventually, on the exit end side, the light incident on the inclined surface of the chamfered portion and refracted is reflected by the inclined surface of the notch portion and is not emitted from the exit end portion to the outside of the substrate. In this way, after the light is refracted away from the optical axis at the inclined surface of the chamfered portion of the emission end portion, the light is incident on the inclined surface of the cutout portion of the emission end portion, and thereby the bottom surface and the inclined surface of the cutout portion. The angle θ ₂ formed by (θ ₂ <90 °) can be reduced. This is because light refracted by the inclined surface of the chamfered portion is incident on the inclined surface of the notched portion, so that the incident angle of the light to the inclined surface of the notched portion is increased and the angle θ ₂ is decreased. This is because the light reflection condition on the inclined surface of the notch can be maintained. As a result, the distance between the emission end and the transmitted light detector can be made closer, and the removal of noise due to dust or the like can be expected.

According to a sixth invention of the present application, in the fifth invention, the angle θ ₂ (θ ₂ <90 °) formed by the bottom surface and the inclined surface of the cutout portion at the emission end portion is the bottom surface and the inclined surface of the chamfered portion at the emission end portion. A microchip having a relationship with an angle θ ₃ formed by (θ ₃ <90 °) larger than each critical θ _x represented by the following formula (2) is provided.

ここで、ｎ₀は基板が載置されている雰囲気の屈折率、
ｎ₁は前記基板の屈折率、
ｎ₂は前記検出路に導入される試料の屈折率。

Where n ₀ is the refractive index of the atmosphere in which the substrate is placed,
n ₁ is the refractive index of the substrate,
n ₂ is the refractive index of the sample introduced into the detection path.

The light exit area is limited to a predetermined area by designing the angle θ ₂ formed by the bottom surface of the notch at the exit end and the inclined surface to be larger than the critical angle θ _x satisfying the relational expression (2). Thus, the sample can be accurately quantified, and the removal of noise due to dust or the like can be expected by reducing the distance between the exit end and the transmitted light detector.
According to a seventh aspect of the present invention, in the first aspect, a chamfered portion is formed on the inner wall of the detection path at the incident end, and the chamfered portion of the incident end is an optical axis of light passing through the detection path. And a side surface including at least one inclined surface surrounding the bottom surface. The concave portion is formed so that the opening of the concave portion becomes narrower toward the bottom surface. Provide a microchip.

  The fact that the opening of the recessed portion becomes narrower toward the bottom surface on the inner wall of the detection path on the incident end side means that the opening of the recessed portion is formed so as to gradually expand along the light emission direction. That is, the inclined surface of the concave portion forming the chamfered portion of the incident end portion is inclined so as to be away from the optical axis with respect to the bottom surface of the concave portion as it goes in the light emitting direction. Therefore, among the light incident on the incident end, the light incident on the inclined surface of the chamfered portion of the incident end is reflected by the inclined surface and does not enter the detection path. On the other hand, of the light incident on the incident end, the light incident on the bottom surface substantially perpendicular to the optical axis passes through the bottom surface of the chamfered portion of the incident end and enters the detection path. Therefore, the emission area of the light emitted from the emission end can be limited to the area of the bottom surface of the recess that forms the chamfered portion of the incidence end. This eliminates an error in the amount of transmitted light due to the difference in the light emission area, and allows the sample to be accurately quantified.

Further, since the light incident on the bottom surface of the concave portion forming the chamfered portion of the incident end portion enters the detection path, the light passes through the central portion of the detection path. Therefore, it is possible to eliminate fluctuations in the amount of transmission due to the bubbles, such as passing near the inner wall of the detection path and being irregularly reflected by the bubbles.
Further, since the inclined surface of the incident end is inclined so as to be away from the optical axis as it goes in the light emitting direction, the light incident on the inclined surface is reflected outward of the detection path and is directed toward the inside of the detection path. Absent. For this reason, it is possible to prevent the light reflected by the inclined surface from affecting the light incident on the bottom surface of the concave portion and changing the light transmission amount.

In an eighth invention of the present application, in the seventh invention, an angle θ ₄ (θ ₄ <90 °) formed by the bottom surface of the chamfered portion of the incident end portion and the inclined surface is a critical angle θ represented by the following formula (3): Provide a microchip larger than _x .

ここで、ｎ₁は前記基板の屈折率、
ｎ₂は前記検出路に導入される試料の屈折率である。
入射端部の面取り部の底面と傾斜面とがなす角θ₄が関係式（３）を満たす臨界角θ_xよりも大きい場合、入射端部の面取り部の傾斜面に入射された光は全反射される。よって、入射端部の面取り部がこのような傾斜面を有する場合には、入射端部に入射された光のうち入射端部の面取り部の傾斜面に入射された光は検出路の外側方向に全反射され、面取り部の底面に入射された光は検出路に入射される。このようにして、出射端部から出射される光の出射面積を所定面積に制限することで、試料を正確に定量することができる。

Where n ₁ is the refractive index of the substrate,
n ₂ is the refractive index of the sample introduced into the detection path.
When the angle θ ₄ formed between the bottom surface of the chamfered portion at the incident end and the inclined surface is larger than the critical angle θ _x satisfying the relational expression (3), all the light incident on the inclined surface of the chamfered portion at the incident end portion Reflected. Therefore, when the chamfered portion of the incident end portion has such an inclined surface, the light incident on the inclined surface of the chamfered portion of the incident end portion of the light incident on the incident end portion is directed outward of the detection path. The light that is totally reflected by the light and incident on the bottom surface of the chamfered portion enters the detection path. In this way, the sample can be accurately quantified by limiting the emission area of the light emitted from the emission end to a predetermined area.

  A ninth invention of the present application is the seventh invention, wherein the incident end further includes a notch on the substrate outer wall corresponding to the other end of the detection path, and the notch of the incident end is A recess is formed that includes a bottom surface that is substantially perpendicular to the optical axis of the light passing through the detection path, and a side surface that includes at least one inclined surface that surrounds the bottom surface. Provided is a microchip formed so as to become narrower toward the surface.

The fact that the opening of the concave portion becomes narrower toward the bottom surface on the outer wall of the incident end portion means that the opening of the concave portion is gradually narrowed in the light emitting direction. That is, the inclined surface of the recess that forms the cutout portion of the incident end portion is inclined so as to approach the optical axis with respect to the bottom surface of the recess as it goes in the light emitting direction. Therefore, of the light incident on the outer wall of the incident end, the light incident on the inclined surface of the notch at the incident end is refracted away from the optical axis and travels through the incident end, Incident on the inclined surface. Eventually, on the incident end side, the light refracted by being incident on the inclined surface of the notch is reflected by the inclined surface of the chamfered portion and does not enter the detection path. Thus, after the light is refracted away from the optical axis at the inclined surface of the notch portion of the incident end portion, it is incident on the inclined surface of the chamfered portion of the incident end portion so that the bottom surface and the inclined surface of the chamfered portion are The formed angle θ ₅ (θ ₅ <90 °) can be reduced. This is because light refracted by the inclined surface of the notch is incident on the inclined surface of the chamfered portion, so that the incident angle of the light to the inclined surface of the chamfered portion increases, and even if the angle θ ₅ is decreased, the chamfering is performed. This is because the light reflection condition on the inclined surface of the portion can be maintained. Thereby, it can be suppressed that light incident on the detection path from the bottom surface of the chamfered portion of the incident end portion is irregularly reflected by the bubbles attached to the inclined surface of the chamfered portion.

According to a tenth aspect of the present invention, in the ninth aspect, the angle θ ₅ (θ ₅ <90 °) formed by the bottom surface and the inclined surface of the chamfered portion at the incident end portion is the bottom surface and the inclined surface of the notched portion at the incident end portion. A microchip having a relationship with an angle θ ₆ formed by (θ ₆ <90 °) larger than each critical θ _x represented by the following formula (4) is provided.

ここで、ｎ₀は基板が載置されている雰囲気の屈折率、
ｎ₁は前記基板の屈折率、
ｎ₂は前記検出路に導入される試料の屈折率である。

Where n ₀ is the refractive index of the atmosphere in which the substrate is placed,
n ₁ is the refractive index of the substrate,
n ₂ is the refractive index of the sample introduced into the detection path.

By designing the angle θ ₅ formed by the bottom surface of the chamfered portion at the incident end and the inclined surface to be larger than the critical angle θ _x satisfying the relational expression (4), the light emission area is limited to a predetermined area. The sample can be accurately quantified, and light incident on the detection path from the bottom surface of the chamfered portion at the incident end can be prevented from being irregularly reflected by bubbles adhering to the inclined surface of the chamfered portion. .

  ADVANTAGE OF THE INVENTION According to this invention, the microchip which can control the transmitted light which passes a cuvette part accurately, can aim at the simplification of a manufacturing process and the reduction of manufacturing cost can be provided.

<Outline of the invention>
The cuvette portion according to the present invention formed in the microchip is formed by a detection path, an incident end portion, and an exit end portion. The detection path is formed inside the substrate, and a sample to be quantified is introduced. The incident end is formed by a substrate at one end of the detection path, and light is incident on the detection path. The emission end is formed by a substrate at the other end of the detection path, and emits light that has passed through the detection path to the outside of the substrate. Here, the cuvette portion is formed to have at least one of a cutout portion at the exit end portion and a chamfered portion at the entrance end portion. The cutout portion at the exit end and the chamfered portion at the entrance end limit the exit area of light exiting from the detection path.

  Here, the amount of transmitted light should depend on the property of the sample introduced into the detection path, but the amount of transmitted light varies depending on the exit area from which the light is emitted. In the present invention, the above-described configuration limits the emission area of the light emitted from the emission end to a desired area. This eliminates an error in the amount of transmitted light due to the difference in the light emission area, and allows the sample to be accurately quantified. In addition, since the incident end and the emission end that limit the light emission area are formed from the substrate integrally with the detection path, the notch or the incident end of the emission end that restricts the light emission area is formed. There is no positional deviation between the chamfered portion and the optical axis of the light passing through the detection path. This also makes it possible to accurately quantify the sample by limiting the emission area of the transmitted light to a desired area. As described above, according to the configuration of the present invention, even a very small amount of sample can be accurately quantified with less error.

The notch at the exit end and / or the chamfered portion at the entrance end that limit the light exit area are formed by notching the same substrate as the detection path, and therefore in the same process as the detection path using injection molding. Can be formed at once. Therefore, it is possible to prevent the displacement of the detection path from the cut-out portion of the emission end portion and / or the chamfered portion of the incident end portion that limits the light emission area from the manufacturing surface.
Also, since the formation of the cut-out portion of the exit end and the chamfered portion of the entrance end and the formation of the detection path are the same process, a special for forming the cut-out portion of the exit end and the chamfer of the entrance end. An unnecessary process is unnecessary, and the manufacturing cost can be reduced. Furthermore, the manufacturing of microchips by injection molding does not require an etching process such as heat treatment for patterning a photoresist, wet etching using an alkaline solution, or dry etching. Therefore, the cuvette portion can be formed even with a material having a relatively low resistance to etching. For example, application to a glass substrate other than a glass substrate can be considered. In addition, since injection molding is less expensive than the etching process as described above, a microchip can be manufactured at low cost.

As described above, by using the microchip of the present invention, the microchip can be easily manufactured while accurately quantifying the sample.
Note that the cut-out portion of the emission end portion and the chamfered portion of the incident end portion can also control the light emission direction so that the light that has passed through the central portion in the cross-sectional direction of the detection path is selectively emitted. . Bubbles may be generated on the inner wall of the detection path when a sample is introduced into the detection path. Due to the bubbles adhering to the inner wall of the detection path, the light passing near the inner wall of the detection path is scattered, and there is a possibility that the amount of transmission of the light detected from the emission end will vary. The cutout portion of the exit end and the chamfered portion of the entrance end of the present invention prevent light that has been affected by passing through the vicinity of the inner wall of the detection path and being diffusely reflected by bubbles from being emitted from the exit end. Only the light that has passed through the central portion of the detection path is emitted. Thereby, the fluctuation | variation of the permeation | transmission amount of the light resulting from the bubble adhering to the inner wall of a detection path can be eliminated, and a sample can be quantified correctly.

<First embodiment>
(1) Overall Configuration of Microchip FIG. 1 is an overall perspective view of a microchip including a cuvette portion according to a first embodiment of the present invention.
The microchip 100 is formed of an upper substrate 100a and a lower substrate 100b which are substrates. The lower substrate 100b of the microchip 100 includes a sample intake port 1, a centrifuge tube 3, a holding unit 5, a measuring unit 7, a waste liquid reservoir 9, a reagent reservoir (11a, 11b) 11 in which a reagent is stored. It has a primary mixing section 13, a secondary mixing section 15 comprising a mixer section, an outlet 17, a cuvette section 20 including a detection path 19, and a micro flow path connecting these sections. Further, the upper substrate 100a of the microchip 100 covers the lower substrate 100b and has an opening penetrating outside the substrate, such as the sample inlet 1 and the outlet 17. As shown in FIG. 1, the microchip 100 separates target components by rotation around the center 1 and the center 2, and performs weighing and mixing with a reagent. Hereinafter, each part will be described on the assumption that the sample to be introduced into the microchip 100 is blood and the plasma contains a component to be quantified.

The intake port 1 takes in blood from the outside of the microchip 100.
The centrifuge tube 3 is generally U-shaped so as to have an opening with respect to the center 1, one open end is connected to the measuring part 7, and the other open end is connected to the intake 1. ing. The centrifuge tube 3 takes in blood from the intake port 1 by rotation around the center 1 and centrifuges plasma containing the target component from the blood. Here, the rotation around the center 1 means that the microchip 100 is rotated around the center 1 and a centrifugal force in a predetermined direction is applied to the liquid inside the microchip 100. The same applies to the center 2 and the center 3.

The holding unit 5 is provided at the bottom of the U-shape of the centrifuge tube 3, and separates and holds blood cells that are components other than the target component from the blood by centrifugation with the center 1. By providing the holding unit 5, it is possible to efficiently separate plasma containing the target component and blood cells that are non-target components.
The measuring unit 7 is connected to the centrifuge tube 3, and blood plasma is introduced from the centrifuge tube 3. The measuring unit 7 is connected to the waste liquid reservoir 9 and has a predetermined volume. Therefore, when an excessive amount of plasma exceeding a predetermined volume is introduced, it is discharged into the waste liquid reservoir 9.

The waste liquid reservoir 9 is connected to the measuring unit 7 and holds an excessive amount of plasma as described above.
The reagent reservoirs 11 a and 11 b are connected to the primary mixing unit 13, and the reagent is introduced in advance before using the microchip 100. Reagents in the reagent reservoirs 11a and 11b are introduced into the primary mixing unit 13 by rotation around the center 1 during centrifugation.
The primary mixing unit 13 is connected to the measuring unit 7 through a micro flow channel, and plasma is introduced from the measuring unit 7. Further, the primary mixing unit 13 is connected to the reagent reservoir 11 in which the reagent is accumulated, and the reagent is introduced. Therefore, in the primary mixing unit 13, the plasma and the reagent are merged and mixed.

The secondary mixing unit 15 is connected to the primary mixing unit 13 and the mixed sample mixed in the primary mixing unit 13 is introduced. The secondary mixing unit 15 is formed by connecting a plurality of H-shaped mixer units in series, and the mixed sample introduced from the primary mixing unit 13 passes through the mixer unit and changes its flow direction. To be further mixed.
The detection path 19 is formed in the cuvette unit 20 and is connected to the secondary mixing unit 15 to introduce a mixed sample of reagent and plasma. When the mixed sample is optically quantified, light is introduced into the detection path 19 from one end of the cuvette portion 20 and light after passing through the detection path 19 is taken out from the other end. Then, the blood component is quantified by measuring the amount of transmitted light.

The outlet 17 takes out the mixed sample in the detection path 19 to the outside of the microchip 100.
(2) Various configurations of the cuvette unit The configuration of the cuvette unit 20 will be described below with various examples.
(2-1) Pattern A
(I) Configuration FIG. 2 is a configuration diagram illustrating an example of the cuvette portion of the pattern A. Here, FIG. 2A is a perspective view of the cuvette portion 20A of the pattern A, FIG. 2B is a cross-sectional view taken along the line A1-A1 ′ of FIG. 2A, and FIG. It is A2-A2 'sectional drawing of (b).

  The cuvette portion 20A is formed of an upper substrate 21a and a lower substrate 21b. The cuvette unit 20A includes a detection path 23, an introduction path 25 for introducing a mixed sample of plasma and reagent into the detection path 23, a discharge path 27 for discharging the mixed sample from the detection path 23, and an incident light incident from outside the substrate. It includes an end portion 29 and an emission end portion 31 that emits light after passing through the detection path 23 to the outside of the substrate.

  The detection path 23 is formed by being surrounded by a groove inside the lower substrate 21b and a lower surface of the upper substrate 21a. Further, the incident end portion 29 is formed by a substrate at one end of the detection path 23, and the emission end portion 31 is formed by a substrate at the other end of the detection path 23. The incident end portion 29 has an incident end outer wall surface 29a that is irradiated with light from the outside of the substrate, and the emission end portion 31 has an emission end outer wall surface that emits light to the outside of the substrate. Here, the incident surface 23 a on which light is incident on the detection path 23 also serves as the inner wall surface of the incident end portion 29, and the exit surface 23 b from which the light passing through the detection path 23 is emitted is emitted from the exit end portion 31. Also serves as the inner wall surface of the end.

  A notch 33 is formed on the outer wall of the emission end 31 of the emission end 31. The notch 33 includes a bottom surface 33-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 23, three inclined surfaces 33-1 that surround the bottom surface 33-2, and a lower surface of the one upper substrate 21a. A side surface including the concave portion. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 33-2. In other words, the inclined surface 33-1 of the recess that forms the notch 33 is inclined away from the optical axis with respect to the bottom surface 33-2 of the recess as it goes in the light emitting direction.

(Ii) Behavior of light in the cuvette part After introducing the mixed sample of plasma and reagent into the detection path 23, the incident end part 29 is irradiated with light and the incident end part 29 is irradiated with light. The The light passes through the incident end portion 29, is introduced from the incident surface 23a into the detection path 23, and passes through the detection path 23 filled with the mixed sample. And the light which passed the inside of the detection path 23 is introduce | transduced into the output end part 31 from the output surface 23b. Next, the light that has passed through the emission end 31 is introduced into the notch 33 on the outer wall of the emission end 31. Here, the bottom surface 33-2 of the recess forming the notch 33 is perpendicular to the optical axis of the light passing through the detection path 23, and the inclined surface 33-1 surrounding the bottom surface 33-2 is relative to the bottom surface 33-2. Tilted away from the optical axis. Therefore, light that has entered the inclined surface 33-1 among the light that has passed through the detection path 23 is reflected and is not emitted from the emission end 31 to the outside of the substrate. On the other hand, of the light that has passed through the detection path 23, the light that has entered the bottom surface 33-2 that is substantially perpendicular to the optical axis passes through the bottom surface 33-2 and is emitted to the outside of the substrate. Therefore, the emission area of the light emitted from the emission end portion 31 to the outside of the substrate can be limited to the area of the bottom surface 33-2 of the recess in the emission end portion 31. Thereby, it is possible to eliminate the error of the light transmission amount due to the difference in the light emission area, and to accurately quantify the blood component to be quantified.

Further, bubbles may be formed on the inner wall of the detection path 23 when a sample is introduced into the detection path 23. However, light that has been affected by being passed through the inner wall of the detection path 23 and being diffusely reflected from the bubble is reflected by the inclined surface 33-1 that surrounds the bottom surface 33-2 of the recess, so that transmission of light due to the bubble is transmitted. Variations in quantity can be eliminated.
Furthermore, since the inclined surface 33-1 of the notch 33 is inclined so as to be away from the optical axis as it goes in the light emitting direction, the light incident on the inclined surface 33-1 is directed outward of the detection path 23. It is reflected and does not go inside the detection path 23. Therefore, it is possible to prevent the light reflected by the inclined surface 33-1 from affecting the light incident on the bottom surface 33-2 of the concave portion and changing the amount of transmitted light.

(Iii) Conditions for total reflection FIG. 3 is an explanatory diagram showing conditions for total reflection of light.
The angle θ _a (θ _a <90 °) formed by the bottom surface 33-2 and the inclined surface 33-1 of the notch 33 is larger than the critical angle θ _x expressed by the following formula (5) (θ _a > θ _x ).

ここで、ｎ₀はキュベット部２０Ａが載置されている雰囲気の屈折率、
ｎ₁は下部基板２１ｂの屈折率である。
出射端部３１の切り欠き部３３における底面３３−２と傾斜面３３−１とがなす角θ_aが関係式（５）を満たす臨界角θ_xよりも大きい場合、切り欠き部３３の傾斜面３３−１に入射された光は全反射される。よって、出射端部３１の切り欠き部３３がこのような傾斜面３３−１を有する場合には、検出路２３を通過した光のうち切り欠き部３３の傾斜面３３−１に入射された光は検出路２３の外側に全反射され、切り欠き部３３の底面３３−２に入射された光は出射端部３１から基板外部に出射される。このようにして、出射端部３１から出射される光の出射面積を所定面積に制限することで、試料を正確に定量することができる。

Here, n ₀ is the refractive index of the atmosphere in which the cuvette portion 20A is placed,
n ₁ is the refractive index of the lower substrate 21b.
When the angle θ _a formed by the bottom surface 33-2 and the inclined surface 33-1 in the notch 33 of the emission end 31 is larger than the critical angle θ _x satisfying the relational expression (5), the inclined surface of the notch 33 The light incident on 33-1 is totally reflected. Therefore, when the cutout portion 33 of the emission end portion 31 has such an inclined surface 33-1, the light incident on the inclined surface 33-1 of the cutout portion 33 among the light that has passed through the detection path 23. Is totally reflected outside the detection path 23, and light incident on the bottom surface 33-2 of the notch 33 is emitted from the emission end 31 to the outside of the substrate. In this way, the sample can be accurately quantified by limiting the emission area of the light emitted from the emission end 31 to a predetermined area.

Here, when the cuvette portion 20A is placed in the air (refractive index n ₀ = 1), the relationship between the refractive index of the substrate forming the cuvette portion 20A and the angle θ _a is as shown in Table 1, for example. .

なお、角θ_aが小さい場合には、キュベット部２０Ａの出射端部３１と、出射端部３１に対応するように配置される透過光の検出器（図示せず）との距離を、より近づけることができ埃等によるノイズを除去することができる。これは、同じ出射面積の場合には角θ_aが小さくなることで、底面３３−２から基板外壁までの距離が短くなるためである。

Note that when the angular theta _a is small, and the emission end 31 of the cuvette portion 20A, the distance between the detector of the transmitted light (not shown) which is disposed so as to correspond to the emission end unit 31, closer and more And noise due to dust or the like can be removed. This is for the same emission area than the corner theta _a decrease is because the distance from the bottom surface 33-2 to the substrate outer wall is shortened.

(2-2) Pattern B
(I) Configuration FIG. 4 is a configuration diagram illustrating an example of the cuvette portion of the pattern B. 4A is a perspective view of the cuvette portion 20B of the pattern B, FIG. 4B is a cross-sectional view along B1-B1 ′ of FIG. 4A, and FIG. It is B2-B2 'sectional drawing of (b).

  The cuvette portion 20B is formed of an upper substrate 41a and a lower substrate 41b. The cuvette unit 20B includes a detection path 43, an introduction path 45 for introducing a mixed sample of plasma and reagent into the detection path 43, a discharge path 47 for discharging the mixed sample from the detection path 43, and an incident light incident from the outside of the substrate. It includes an end portion 49 and an emission end portion 51 that emits light after passing through the detection path 43 to the outside of the substrate.

  The detection path 43 is formed by being surrounded by a groove inside the lower substrate 41b and a lower surface of the upper substrate 41a. The incident end 49 is formed by a substrate at one end of the detection path 43, and the emission end 51 is formed by a substrate at the other end of the detection path 43. The incident end portion 49 has an incident end outer wall surface 49a that is irradiated with light from outside the substrate, and the emission end portion 51 has an emission end outer wall surface that emits light to the outside of the substrate. Here, the incident surface 43 a for entering the light into the detection path 43 also serves as the inner wall surface of the incident end portion of the incident end portion 49, and the exit surface from which the light that has passed through the detection path 43 is emitted is the exit end of the exit end portion 51. It also serves as the internal wall.

  A chamfer 43 b is formed on the inner wall surface of the emission end 51. The chamfered portion 43b includes a bottom surface 43b-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 43, three inclined surfaces 43b-1 that surround the bottom surface 43b-2, and a single lower surface of the upper substrate 41a. It is formed so as to have a side surface and a concave portion. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 43b-2. In other words, the inclined surface 43b-1 of the recess that forms the chamfered portion 43b of the emission end 51 is inclined so as to approach the optical axis with respect to the bottom surface 43b-2 of the recess as it goes in the light emission direction.

  A notch 53 is formed in the outer wall of the emission end 51 of the emission end 51. The notch 53 includes a bottom surface 53-2 substantially perpendicular to the optical axis of the light passing through the detection path 43, three inclined surfaces 53-1 surrounding the bottom surface 53-2, and a lower surface of the one upper substrate 41a. A side surface including the concave portion. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 53-2. In other words, the inclined surface 53-1 of the recess that forms the notch 53 is inclined away from the optical axis with respect to the bottom surface 53-2 of the recess as it goes in the light emitting direction.

(Ii) Behavior of light in the cuvette part The light that has passed through the detection path 43 filled with the mixed sample of plasma and reagent enters the chamfered part 43 b of the emission end part 51. Here, the bottom surface 43b-2 of the concave portion forming the chamfered portion 43b is perpendicular to the optical axis of the light passing through the detection path 43, and the inclined surface 43b-1 surrounding the bottom surface 43b-2 is relative to the bottom surface 43b-2. It is inclined to approach the optical axis. Therefore, of the light that has passed through the detection path 43, the light incident on the inclined surface 43b-1 of the chamfered portion 43b of the emission end 51 is refracted away from the optical axis, travels through the emission end, and is cut out. 53 is incident on the inclined surface 53-1. Eventually, the light incident and refracted on the inclined surface 43b-1 of the chamfered portion 43b on the emission end side is reflected by the inclined surface 53-1 of the notch 53 and is not emitted from the emission end 51 to the outside of the substrate. . In this way, after the light is refracted away from the optical axis by the inclined surface 43 b-1 of the chamfered portion 43 b of the emission end 51, the light is incident on the inclined surface 53-1 of the notch 53 of the emission end 51. Thus, the angle θ _b (θ _b <90 °) formed by the bottom surface 53-2 and the inclined surface 53-1 of the notch 53 can be reduced. This is because the light refracted by the inclined surface 43 b-1 of the chamfered portion 43 b is incident on the inclined surface 53-1 of the notched portion 53, so that the incident angle of the light to the inclined surface 53-1 of the notched portion 53. increases, because by reducing the angle theta _b can maintain the reflection conditions of light at the inclined surface 53-1 also notches 53. As a result, the distance between the emission end 51 and the transmitted light detector (not shown) can be made closer, and the removal of noise due to dust or the like can be expected.

  The light incident on the bottom surface 43b-2 of the chamfered portion 43b is incident on the exit end portion 51 without being refracted. Of the light incident on the exit end 51, the light incident on the inclined surface 53-1 of the notch 53 is reflected outside the detection path 43 and is incident on the bottom surface 53-2 of the notch 53. The emitted light is emitted from the emission end 51 to the outside of the substrate. In this way, since the emission area of the light emitted from the emission end 51 is limited to the area of the bottom surface 53-2 of the recess of the notch 53, the amount of transmitted light due to the different light emission areas. Thus, the sample can be accurately quantified.

Further, bubbles may adhere to the inner wall of the detection path 43 when the sample is introduced into the detection path 43. However, light that has been affected by, for example, being reflected near the inner wall of the detection path 43 and being diffusely reflected from the bubble is reflected by the inclined surface 53-1 of the notch 53, so that the amount of transmitted light due to the bubble varies. Can be eliminated.
Furthermore, since the inclined surface 53-1 of the notch 53 is inclined so as to be away from the optical axis as it goes in the light emitting direction, the light incident on the inclined surface 53-1 is directed outward of the detection path 43. It is reflected and does not go inside the detection path 43. Therefore, it is possible to prevent the light reflected by the inclined surface 53-1 from affecting the light incident on the bottom surface 53-2 of the concave portion and changing the light transmission amount.

Note that the area of the bottom surface 43b-2 of the chamfered portion 43b and the area of the bottom surface 53-2 of the cutout portion 53 are preferably the same in order to make the light emission area constant.
(Iii) Conditions for Total Reflection FIG. 5 (a) is an explanatory diagram showing conditions for the total reflection of light, and FIG. 5 (b) is an enlarged view of FIG. 5 (a).

In FIG. 5A, the angle θ _b (θ _b <90 °) formed by the bottom surface 53-2 of the notch 53 and the inclined surface 53-1 at the emission end 51 is equal to the chamfered portion 43 b at the emission end 51. The relationship between the angle θ _c (θ _c <90 °) formed by the bottom surface 43b-2 and the inclined surface 43b-1 is larger than each critical θ _x expressed by the following formula (6) (θ _b > θ _x ).

ここで、ｎ₀はキュベット部２０Ｂが載置されている雰囲気の屈折率、
ｎ₁は下部基板４１ｂの屈折率、
ｎ₂は検出路４３に導入される試料の屈折率である。

Here, n ₀ is the refractive index of the atmosphere in which the cuvette portion 20B is placed,
n ₁ is the refractive index of the lower substrate 41b,
n ₂ is the refractive index of the sample introduced into the detection path 43.

When the angle θ _b formed by the bottom surface 53-2 of the notch 53 and the inclined surface 53-1 is larger than the critical angle θ _x satisfying the relational expression (6), the light enters the inclined surface 53-1 of the notch 53. The reflected light is totally reflected outside the detection path 43. Therefore, the sample can be accurately quantified by limiting the light emission area to a predetermined area.
Specifically, this will be described with reference to FIG.

  The relationship between the refractive indices of the light incident on the interface between the detection path 43 and the emission end 51 and the light incident on the emission end 51 from the interface is expressed by the following equation (7).

ここで、角θ_cは、検出路４３と出射端部５１との界面に入射される光が界面の垂直線となす角であり、前述の面取り部４３ｂの底面４３ｂ−２及び傾斜面４３ｂ−１がなす角θ_cと同じである。また、角θ_dは、界面から出射端部５１に入射された光が界面の垂直線となす角である。

Here, the angle θ _c is an angle formed by light incident on the interface between the detection path 43 and the emission end 51 and a vertical line of the interface, and the bottom surface 43b-2 and the inclined surface 43b− of the chamfered portion 43b described above. It is the same as the angle θ _c formed by 1. Further, the angle θ _d is an angle formed by the light incident on the emission end portion 51 from the interface with the vertical line of the interface.

  Further, the relationship between the refractive indexes of the light incident on the interface between the emission end 51 and the outside of the substrate and the light emitted from the interface to the outside of the substrate is expressed by the following equation (8).

ここで、角θ_b＋θ_c−θ_dは、出射端部５１と基板外部との界面に入射される光が界面の垂直線となす角である。また、角θ_eは、界面から基板外部に出射された光が界面の垂直線となす角である。

Here, the angle θ _b + θ _c −θ _d is an angle formed by light incident on the interface between the emission end portion 51 and the outside of the substrate and a vertical line of the interface. The angle θ _e is an angle formed by light emitted from the interface to the outside of the substrate and a vertical line of the interface.

For light is totally reflected by the inclined surface 53-1, angle theta _e in the formula (8) must be 90 ° or more. Therefore, in the equation (8), the angle θ _b when the angle θ _e = 90 ° is the critical angle θ _x , and the above equation (6) is obtained.
Here, when the cuvette portion 20B is placed in the air (refractive index n ₀ = 1), the refractive index of the sample is n ₂ = 1.33, and the angle θ _c = 45 °, the cuvette portion 20B is formed. The relationship between the refractive index n _{1 of the} substrate and the angle θ _b is as shown in Table 2, for example.

なお、角θ_bが小さい場合には、キュベット部２０Ｂの出射端部５１と、出射端部５１に対応するように配置される透過光の検出器（図示せず）との距離を、より近づけることができ埃等によるノイズを除去することができる。これは、同じ出射面積の場合には角θ_bが小さくなることで、底面５３−２から基板外壁までの距離が短くなるためである。

When the angle θ _b is small, the distance between the emission end 51 of the cuvette portion 20B and the transmitted light detector (not shown) arranged so as to correspond to the emission end 51 is made closer. And noise due to dust or the like can be removed. This is for the same emission area than the corner theta _b becomes smaller is because the distance from the bottom surface 53-2 to the substrate outer wall is shortened.

As described above, when the angle θ _b formed by the bottom surface 53-2 of the notch 53 and the inclined surface 53-1 is larger than the critical angle θ _x satisfying the relational expression (6), the light emission area is limited to a predetermined area. Thus, the sample can be accurately quantified, and the removal of noise due to dust or the like can be expected by reducing the distance between the emission end 51 and the transmitted light detector (not shown).
As described above, the configuration of the pattern B in which the cutout portion and the chamfered portion are provided at the emission end portion can be expected to remove noise than the configuration of the pattern A in which only the cutout portion is provided at the emission end portion. There is a possibility that light in the detection path is irregularly reflected by bubbles adhering to the inclined surface of the chamfered portion of the pattern B. However, if the liquid introduced into the detection path has high wettability and bubbles are unlikely to be generated, or if the generation of bubbles is suppressed by mixing a surfactant, etc., noise can be obtained by adopting pattern B. The effect of removal can be utilized more.

(2-3) Pattern C
(I) Configuration FIG. 6 is a configuration diagram illustrating an example of the cuvette portion of the pattern C. Here, FIG. 6A is a perspective view of the cuvette portion 20C of the pattern C, FIG. 6B is a cross-sectional view taken along the line C1-C1 ′ of FIG. 6A, and FIG. It is C2-C2 'sectional drawing of (b).

  The cuvette portion 20C is formed of an upper substrate 61a and a lower substrate 61b. The cuvette portion 20C includes a detection path 63, an introduction path 65 for introducing a mixed sample of plasma and reagent into the detection path 63, a discharge path 67 for discharging the mixed sample from the detection path 63, and an incident light incident from outside the substrate. It includes an end portion 69 and an emission end portion 71 that emits light after passing through the detection path 63 to the outside of the substrate.

  The detection path 63 is formed by being surrounded by a groove inside the lower substrate 61b and a lower surface of the upper substrate 61a. The incident end portion 69 is formed by a substrate at one end of the detection path 63, and the emission end portion 71 is formed by a substrate at the other end of the detection path 63. The incident end portion 69 has an incident end outer wall surface 69a that is irradiated with light from outside the substrate, and the emission end portion 71 has an emission end outer wall surface 71a that emits light to the outside of the substrate. Here, the incident surface on which light is incident on the detection path 63 also serves as the inner wall surface of the incident end portion of the incident end portion 69, and the exit surface 63 b from which the light that has passed through the detection path 63 is emitted is the exit end of the exit end portion 71. It also serves as the internal wall.

  A chamfered portion 63 a is formed on the inner wall surface of the incident end portion 69. The chamfered portion 63a includes a bottom surface 63a-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 63, three inclined surfaces 63a-1 that surround the bottom surface 63a-2, and a single lower surface of the upper substrate 61a. It is formed so as to have a side surface and a concave portion. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 63a-2. In other words, the inclined surface 63a-1 of the recess that forms the chamfered portion 63a is inclined so as to be away from the optical axis with respect to the bottom surface 63a-2 of the recess as it goes in the light emitting direction.

(Ii) Behavior of light in the cuvette part After introducing the mixed sample of plasma and reagent into the detection path 63, the incident end part outer wall surface 69 a of the incident end part 69 is irradiated with light, and the incident light is incident on the incident end part 69. The The light passes through the incident end portion 69 and enters the detection path 63. Here, the bottom surface 63a-2 of the concave portion forming the chamfered portion 63a is perpendicular to the optical axis of the light passing through the detection path 63, and the inclined surface 63a-1 surrounding the bottom surface 63a-2 is relative to the bottom surface 63a-2. Inclined away from the optical axis. Therefore, light incident on the inclined surface 63 a-1 among light incident on the incident end portion 69 is reflected and does not enter the detection path 63. Of the light incident on the incident end 69, the light incident on the bottom surface substantially perpendicular to the optical axis passes through the bottom surface 63 a-2 and enters the detection path 63. Therefore, the emission area of the light emitted from the emission end portion 71 can be limited to the area of the bottom surface 63a-2 of the chamfered portion 63a of the incidence end portion 69. This eliminates an error in the amount of transmitted light due to the difference in the light emission area, and allows the sample to be accurately quantified.

Further, bubbles may be formed on the inner wall of the detection path 63 when the sample is introduced, but the light incident on the bottom surface 63a-2 of the chamfered portion 63a is incident on the detection path 63. Pass through the central part of 63. Therefore, it is possible to eliminate fluctuations in the transmission amount due to the bubbles, such as passing through the vicinity of the inner wall of the detection path 63 and being irregularly reflected from the bubbles.
Furthermore, since the inclined surface 63a-2 of the incident end portion 69 is inclined so as to be separated from the optical axis as it goes in the light emitting direction, the light incident on the inclined surface 63a-1 is directed outward of the detection path 63. It is reflected and does not go inside the detection path 63. Therefore, it is possible to prevent the light reflected by the inclined surface 63a-1 from affecting the light incident on the bottom surface 63a-2 of the recess and changing the light transmission amount.

Note that when the light emission area is limited by the chamfered portion 63a of the incident end portion 69 as described above, the light emission end portion 71 and the transmission end portion are transmitted rather than the light emission area being limited by the cutout portion of the emission end portion. It is possible to expect further removal of noise by bringing the light detector closer.
(Iii) Conditions for total reflection FIG. 7 is an explanatory diagram showing conditions for total reflection of light.

An angle θ _f (θ _f <90 °) formed by the bottom surface 63a-2 of the chamfered portion 63a and the inclined surface 63a-1 is larger than each critical θ _x expressed by the following formula (9) (θ _f > θ _x ).

ここで、ｎ₁は下部基板６１ｂの屈折率、
ｎ₂は検出路６３に導入される試料の屈折率である。
面取り部６３ａの底面６３ａ−２と傾斜面６３ａ−１とがなす角θ_fが関係式（９）を満たす臨界角θ_xよりも大きい場合、面取り部６３の傾斜面６３ａ−１に入射された光は全反射される。よって、入射端部６９の面取り部６３ａがこのような傾斜面６３ａ−１を有する場合には、入射端部６９に入射された光のうち面取り部６３ａの傾斜面６３ａ−１に入射された光は検出路６３の外側方向に全反射され、面取り部６３ａの底面６３ａ−２に入射された光は検出路６３に入射される。このようにして、出射端部７１から出射される光の出射面積を所定面積に制限することで、試料を正確に定量することができる。

Here, n ₁ is the refractive index of the lower substrate 61b,
n ₂ is the refractive index of the sample introduced into the detection path 63.
When the angle θ _f formed by the bottom surface 63a-2 of the chamfered portion 63a and the inclined surface 63a-1 is larger than the critical angle θ _x satisfying the relational expression (9), the light is incident on the inclined surface 63a-1 of the chamfered portion 63. The light is totally reflected. Therefore, when the chamfered portion 63a of the incident end portion 69 has such an inclined surface 63a-1, light incident on the inclined surface 63a-1 of the chamfered portion 63a out of the light incident on the incident end portion 69. Is totally reflected in the outer direction of the detection path 63, and the light incident on the bottom surface 63 a-2 of the chamfered portion 63 a enters the detection path 63. Thus, the sample can be accurately quantified by limiting the emission area of the light emitted from the emission end 71 to a predetermined area.

Here, when the cuvette portion 20C is placed in the air (refractive index n ₀ = 1), the relationship between the refractive index of the substrate forming the cuvette portion 20C and the angle θ _f is as shown in Table 3, for example. .

なお、角θ_fが小さい場合には、検出路４３を通過する光が傾斜面６３ａ−１に付着した気泡により乱反射されるのを抑制することができる。これは、角θ_fが小さくなることで、検出路に入射された光の光軸と傾斜面６３ａ−１とのなす角が大きくなり、光軸と傾斜面６３ａ−１上の気泡との距離が大きくなり気泡の影響が小さくなるためである。

When the angle θ _f is small, it is possible to prevent light passing through the detection path 43 from being irregularly reflected by bubbles adhering to the inclined surface 63a-1. This is because the angle formed between the optical axis of the light incident on the detection path and the inclined surface 63a-1 increases as the angle θ _f decreases, and the distance between the optical axis and the bubbles on the inclined surface 63a-1. This is because the effect of bubbles is reduced.

(2-4) Pattern D
(I) Configuration FIG. 8 is a configuration diagram illustrating an example of the cuvette portion of the pattern D. Here, FIG. 8A is a perspective view of the cuvette portion 20D of the pattern D, FIG. 8B is a cross-sectional view taken along the line D1-D1 ′ of FIG. 8A, and FIG. It is D2-D2 'sectional drawing of (b).

  The cuvette portion 20D is formed of an upper substrate 81a and a lower substrate 81b. The cuvette unit 20D includes a detection path 83, an introduction path 85 for introducing a mixed sample of plasma and reagent into the detection path 83, a discharge path 87 for discharging the mixed sample from the detection path 83, and an incident light incident from outside the substrate. It includes an end portion 89 and an emission end portion 91 that emits light after passing through the detection path 83 to the outside of the substrate.

  The detection path 83 is formed by being surrounded by a groove inside the lower substrate 81b and a lower surface of the upper substrate 81a. Further, the incident end portion 89 is formed by a substrate at one end of the detection path 83, and the emission end portion 91 is formed by a substrate at the other end of the detection path 83. The incident end 89 has an incident end outer wall surface that is irradiated with light from the outside of the substrate, and the emission end 91 has an emission end outer wall surface 91a that emits light to the outside of the substrate. Here, the incident surface on which the light is incident on the detection path 83 also serves as the inner wall surface of the incident end portion of the incident end portion 89, and the exit surface 83 b from which the light that has passed through the detection path 83 is emitted is the exit end of the exit end portion 91. It also serves as the internal wall.

  A cutout portion 93 is formed on the outer wall of the incident end portion of the incident end portion 89. The notch 93 includes a bottom surface 93-2 substantially perpendicular to the optical axis of the light passing through the detection path 83, three inclined surfaces 93-1 surrounding the bottom surface 93-2, and the lower surface of the one upper substrate 21a. A side surface including the concave portion. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 93-2. In other words, the inclined surface 93-1 of the recess that forms the notch 93 of the incident end 89 is inclined so as to approach the optical axis with respect to the bottom surface 93-2 of the recess as it goes in the light emission direction. .

  A chamfered portion 83 a is formed on the inner wall surface of the incident end portion of the incident end portion 89. The chamfered portion 83a includes a bottom surface 83a-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 83, three inclined surfaces 83a-1 that surround the bottom surface 83a-2, and a single lower surface of the upper substrate 81a. It is formed so as to have a side surface and a concave portion. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 83a-2. In other words, the inclined surface 83a-1 of the recess that forms the chamfered portion 83a is inclined away from the optical axis with respect to the bottom surface 83a-2 of the recess as it goes in the light emission direction.

(Ii) Behavior of light in the cuvette portion First, light that has passed through the incident end portion 89 is introduced into the notch 93 of the outer wall of the incident end portion 89. Here, the bottom surface 93-2 of the recess that forms the notch 83 is perpendicular to the optical axis, and the inclined surface 93-1 that surrounds the bottom surface 93-2 extends to the bottom surface 93-2 of the recess as it goes in the light emission direction. In contrast, it is inclined to approach the optical axis. Therefore, out of the light incident on the outer wall of the incident end portion 89, the light incident on the inclined surface 93-1 of the cutout portion 93 of the incident end portion 89 is refracted away from the optical axis and is incident on the inside of the incident end portion. , And enters the inclined surface 83a-1 of the chamfered portion 83a. Eventually, on the incident end side, the light refracted by being incident on the inclined surface 93-1 of the notch 93 is reflected by the inclined surface 83 a-1 of the chamfered portion 83 a and is not incident on the detection path 83. In this way, light is refracted away from the optical axis by the inclined surface 93-1 of the notch 93 of the incident end 89 and then incident on the inclined surface 83 a-1 of the chamfer 83 a of the incident end 89. Thus, the angle θ _g (θ _g <90 °) formed by the bottom surface 83a-2 and the inclined surface 83a-1 of the chamfered portion 83a can be reduced. This is because the light refracted by the inclined surface 93-1 of the notch 93 is incident on the inclined surface 83 a-1 of the chamfered portion 83 a, so that the incident angle of the light to the inclined surface 83 a-1 of the chamfered portion 83 a is increased. increased and, also to reduce the angle theta _g is because it is possible to maintain the reflection conditions of light at the inclined surface 83a-1 of the chamfered portion 83a. As a result, the light incident on the detection path 83 from the bottom surface 83a-2 of the chamfered portion 83a can be suppressed from being irregularly reflected by the bubbles attached to the inclined surface 83a-1 of the chamfered portion 83a.

  The light incident on the bottom surface 93-2 of the cutout portion 93 is incident on the incident end portion 89 without being refracted. Of the light incident on the incident end 89, the light incident on the inclined surface 83a-1 of the chamfer 83a is reflected outside the detection path 83 and is incident on the bottom surface 83a-2 of the chamfer 83a. Light enters the detection path 83. In this way, since the emission area of the light emitted from the emission end portion 91 is limited to the area of the bottom surface 83a-2 of the chamfered portion 83a, an error in the amount of transmitted light due to the difference in the light emission area. The sample can be accurately quantified.

  Further, bubbles may be formed on the inner wall of the detection path 83 when the sample is introduced into the detection path 83. However, since the light emission direction is limited by the incident end 89 having the notch 93 and the chamfer 83a, the light passes through the central portion of the optical axis of the detection path 83 and passes near the inner wall of the detection path 83. do not do. Therefore, the light is emitted from the emission end portion 91 without being influenced by being diffusely reflected by the bubbles. Thereby, the fluctuation | variation of the permeation | transmission amount of the light resulting from a bubble can be eliminated.

  Furthermore, since the inclined surface 83a-1 of the chamfered portion 83a is inclined so as to be away from the optical axis as it goes in the light emitting direction, the light incident on the inclined surface 83a-1 is reflected in the outer direction of the detection path 83. And does not go into the detection path 83. Therefore, it is possible to prevent the light reflected by the inclined surface 83a-1 from affecting the light incident on the bottom surface 83a-2 of the recess and changing the light transmission amount.

As described above, when the light emission area is limited by the chamfered portion 83a of the incident end portion 89, the light is transmitted through the emission end portion 91 and transmitted more than when the light emission area is limited by the cutout portion of the emission end portion. It is possible to expect further removal of noise by bringing the light detector closer.
In addition, it is preferable that the area of the bottom face 93-2 of the notch part 93 and the area of the bottom face 83a-2 of the chamfered part 83a are the same in order to make the light emission area constant.

(Iii) Conditions for total reflection FIG. 9 is an explanatory diagram showing conditions for the total reflection of light.
In FIG. 9, the angle θ _g (θ _g <90 °) formed by the bottom surface 83 a-2 of the chamfered portion 83 a and the inclined surface 83 a-1 at the incident end portion 93 is the bottom surface 93-of the notch portion 93 at the incident end portion 93. 2 and the angle θ _h (θ _h <90 °) formed by the inclined surface 93-1 is larger than each critical θ _x represented by the following formula (10) (θ _g > θ _x ).

ここで、ｎ₀はキュベット部２０Ｄが載置されている雰囲気の屈折率、
ｎ₁は下部基板８１ｂの屈折率、
ｎ₂は検出路８３に導入される試料の屈折率である。

Here, n ₀ is the refractive index of the atmosphere in which the cuvette portion 20D is placed,
n ₁ is the refractive index of the lower substrate 81b,
n ₂ is the refractive index of the sample introduced into the detection path 83.

When the angle θ _g formed between the bottom surface 83a-2 of the chamfered portion 83a and the inclined surface 83a-1 is larger than the critical angle θ _x satisfying the relational expression (10), the light is incident on the inclined surface 83a-1 of the chamfered portion 83a. The light is totally reflected outside the detection path 83. Therefore, the sample can be accurately quantified by limiting the light emission area to a predetermined area. Since the specific calculation method of the above formula is the same as that described above for the cuvette portion 20B of the pattern B, description thereof will be omitted.

Here, when the cuvette portion 20D is placed in the air (refractive index n ₀ = 1), the refractive index of the sample is n ₂ = 1.33, and the angle θ _h = 45 °, the cuvette portion 20D is formed. The relationship between the refractive index n _{1 of the} substrate and the angle θ _g is as shown in Table 4, for example.

なお、角θ_gが小さい場合には、検出路８３を通過する光が傾斜面８３ａ−１に付着した気泡により乱反射されるのを抑制することができる。これは、角θ_gが小さくなることで、検出路に入射された光の光軸と傾斜面８３ａ−１とのなす角が大きくなり、光軸と傾斜面８３ａ−１上の気泡との距離が大きくなり気泡の影響が小さくなるためである。

When the angle θ _g is small, it is possible to prevent light passing through the detection path 83 from being irregularly reflected by bubbles attached to the inclined surface 83a-1. This is because the angle theta _g decreases, the angle becomes larger with the optical axis of the incident on the detection path light and the inclined surface 83a-1, the distance between the optical axis and the bubbles on the inclined surface 83a-1 This is because the effect of bubbles is reduced.

  Further, the configuration of the putter D in which the cut-out portion and the chamfered portion are provided at the incident end is less likely to cause light to be diffusely reflected by the bubbles attached to the inclined surface of the chamfered portion than the configuration of the pattern C in which only the chamfered portion is provided at the incident end. Therefore, it is preferable. However, in the case of the pattern D, the distance from the device that irradiates the cuvette portion with incident light to the bottom surface of the notch becomes longer than the configuration of the pattern C by the amount of the notch. Therefore, incident light may be affected by noise due to dust or the like. When the influence of such noise is small, the effect that the light is hardly diffused can be further utilized by adopting the pattern D.

(2-5) Pattern E
(I) Configuration FIG. 10 is a configuration diagram illustrating an example of the cuvette portion of the pattern E. 10A is a perspective view of the cuvette portion 20E of the pattern E, FIG. 10B is an E1-E1 ′ sectional view of FIG. 10A, and FIG. It is E2-E2 'sectional drawing of (b).

The cuvette portion 20E of the pattern E is a combination of the cuvette portion 20A of the pattern A and the cuvette portion 20C of the pattern C, and the configuration will be briefly described below.
The cuvette portion 20E is formed of an upper substrate 101a and a lower substrate 101b. The cuvette portion 20E includes a detection path 103, an introduction path 105, a discharge path 107, an incident end 109 formed by a substrate at one end of the detection path 103, and an emission end formed by a substrate at the other end of the detection path 103. Part 111 is included.

  A notch 113 is formed in the outer wall of the emission end 111. The notch 113 includes a bottom surface 113-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 103, three inclined surfaces 113-1 that surround the bottom surface 113-2, and the bottom surface of the one upper substrate 101a. It is formed so as to have a concave portion including a side surface including the side surface. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 113-2.

  A chamfered portion 103 a is formed on the inner wall surface of the incident end portion 109. The chamfered portion 103a has a recess composed of a bottom surface 103a-2 that is substantially perpendicular to the optical axis, three inclined surfaces 103a-1 that surround the bottom surface 103a-2, and a side surface that includes the lower surface of the upper substrate 101a. It is formed as follows. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 103a-2.

In the case of the pattern E, in order to totally reflect light at the incident end and the emission end, it is necessary to satisfy the relational expressions in the patterns A and C.
(Ii) Behavior of light in the cuvette portion The behavior of light in the cuvette portion 20E is the same as that of the cuvette portion 20A of the pattern A and the cuvette C of the pattern C described above. In this cuvette portion 20E configuration, the following operational effects can be obtained in addition to the operational effects obtained by the cuvette portion 20A of the pattern A and the cuvette portion 20C of the pattern C.

  In the cuvette portion 20E, the emission area of the light emitted from the emission end portion 113 is first limited to the area of the bottom surface 103a-2 of the concave portion of the chamfered portion 103a of the incidence end portion 109, and further the notch portion of the emission end portion 111. The area of the bottom surface 113-2 of the recess 113 is limited. Therefore, even after the light exit area is limited by the chamfered portion 103a of the incident end portion 109, even when the light spreads away from the optical axis while passing through the detection path 103 and the exit end portion 111, again, The emission area is limited by the notch 113. This eliminates an error in the amount of transmitted light due to the difference in the light emission area, and allows the sample to be accurately quantified.

  Further, the light passes through the center portion of the detection path 103 by passing through the bottom surface 103 a-2 of the chamfered portion 103 a at the incident end portion 109. Here, the light may approach the inner wall of the detection path 103 while passing through the detection path 103. However, since the light approaching the inner wall of the detection path 103 is reflected by the inclined surface 113-1 of the cutout portion 113 at the emission end portion 111, fluctuations in the amount of transmitted light due to the bubbles can be eliminated.

  Further, both the opening of the concave portion forming the chamfered portion 103a and the opening of the concave portion forming the cutout portion 113 are formed so as to gradually spread in the light emitting direction. Therefore, first, the light incident on the inclined surface 103 a-1 is reflected toward the outside of the substrate and does not travel toward the detection path 103. Furthermore, even when the light spreads away from the optical axis while passing through the detection path 103 and the emission end 111, the light incident on the inclined surface 113-1 is reflected in the outer direction of the detection path 43, It does not go to the inside of the detection path 43. Therefore, it is possible to prevent the light reflected by the inclined surface 103a-1 and the inclined surface 113-1 from changing the amount of transmitted light.

(Iii) Design Example FIG. 11 is an explanatory diagram showing a design example of the cuvette portion 20E in the pattern E. Here, the dimensions of each part of the cuvette part 20E are as follows.
a (incident end outer wall surface 109a to bottom surface 103a-2) = 0.5 mm
b (distance where the inclined surface 103a-1 is inclined) = 0.7 mm
c (Length of detection path: bottom surface 103a-2 to emission end portion inner wall surface 103b) = 10.0 mm
d (outgoing end inner wall surface 103b to bottom surface 113-2) = 0.5 mm
e (bottom surface 113-2 to incident end outer wall surface) = 0.5 mm
f (width of the bottom surface 103a-2 and the bottom surface 113-2) = 0.7 mm
g (maximum width of the opening of the notch 113) = 1.9 mm
h (width of detection path 103) = 1.5 mm
i (depth of detection path 103) = 1.5 mm
W (width of incident light incident on the outer wall surface 109a of the incident end from the outside of the substrate) = 1.0 mm
Here, in order to obtain the effects of the present invention as described above, it is necessary that W> f.

In addition, the said dimension is an example to the last and is not limited to the said dimension.
(2-6) Pattern F
(I) Configuration FIG. 12 is a configuration diagram illustrating an example of the cuvette portion of the pattern F. Here, FIG. 12A is a perspective view of the cuvette portion 20F of the pattern F, FIG. 12B is a F1-F1 ′ sectional view of FIG. 12A, and FIG. It is F2-F2 'sectional drawing of (b).

The cuvette portion 20F of the pattern F is a combination of the cuvette portion 20B of the pattern B and the cuvette portion 20D of the pattern D, and the configuration will be briefly described below.
The cuvette portion 20F is formed of an upper substrate 121a and a lower substrate 121b. The cuvette portion 20E includes a detection path 123, an introduction path 125, a discharge path 127, an incident end 129 formed by a substrate at one end of the detection path 123, and an emission end formed by a substrate at the other end of the detection path 123. Part 131.

  A notch 143 is formed on the incident end outer wall of the incident end 129. The notch 143 includes a bottom surface 143-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 123, three inclined surfaces 143-1 that surround the bottom surface 143-2, and a lower surface of the one upper substrate 121a. A side surface including the concave portion. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 143-2. A chamfered portion 123 a is formed on the inner wall surface of the incident end portion 129. The chamfered portion 123a has a recess composed of a bottom surface 123a-2 that is substantially perpendicular to the optical axis, three inclined surfaces 123a-1 that surround the bottom surface 123a-2, and a side surface that includes the lower surface of one upper substrate 121a. It is formed as follows. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 123a-2.

  A chamfered portion 123 b is formed on the inner wall surface of the emission end portion 131. The chamfered portion 123b has a recess composed of a bottom surface 123b-2 that is substantially perpendicular to the optical axis, three inclined surfaces 123b-1 that surround the bottom surface 123b-2, and a side surface that includes the lower surface of the upper substrate 121a. It is formed as follows. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 123b-2. In addition, a notch 133 is formed in the outer wall of the emission end portion of the emission end portion 131. The notch 133 has a recess composed of a bottom surface 133-2 that is substantially perpendicular to the optical axis, and three inclined surfaces 133-1 that surround the bottom surface 133-2 and a side surface that includes the lower surface of the upper substrate 21a. It is formed as follows. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 133-2.

In the case of the pattern F, in order to totally reflect the light at the incident end and the emission end, it is necessary to satisfy the relational expressions in the patterns B and D.
(Ii) Behavior of light in the cuvette portion The behavior of light in the cuvette portion 20F is the same as that of the cuvette portion 20B of the pattern B and the cuvette portion 20D of the pattern D described above. In this cuvette portion 20F configuration, the following operational effects can be obtained in addition to the operational effects obtained by the pattern B cuvette portion 20B and the pattern D cuvette portion 20D.

  In the cuvette portion 20F, the emission area of the light emitted from the emission end portion 113 includes the area of the bottom surface 123a-2 of the concave portion of the chamfered portion 123a of the incident end portion 129 and the bottom surface of the concave portion of the notch portion 133 of the emission end portion 111. The area is limited to 133-2. That is, even when the light spreads away from the optical axis, the spread light is always reflected and removed, so that the light emission area at the emission end 131 is limited. This eliminates an error in the amount of transmitted light due to the difference in the light emission area, and allows the sample to be accurately quantified.

  Further, the light passes through the center portion of the detection path 123 by passing through the bottom surface 123a-2 of the chamfered portion 123a at the incident end portion 129. Here, the light may approach the inner wall of the detection path 103 while passing through the detection path 123. However, since the light approaching the inner wall of the detection path 123 is reflected by the inclined surface 133-1 of the notch 133 at the emission end 131, fluctuations in the amount of transmitted light due to the bubbles can be eliminated.

  Further, the chamfered portion 123a of the incident end portion 129 and the cutout portion 133 of the emission end portion 131 are formed so that the opening gradually widens in the light emission direction. Therefore, first, the light incident on the inclined surface 123 a-1 is reflected in the outer direction of the detection path 123 and does not go to the detection path 123. Further, even when light spreads away from the optical axis while passing through the detection path 123 and the emission end 131, the light incident on the inclined surface 133-1 is reflected in the outer direction of the detection path 123, It does not go to the inside of the detection path 123. Therefore, it is possible to prevent the light reflected by the inclined surface 123a-1 and the inclined surface 133-1 from changing the amount of transmitted light.

(Iii) Example of Design FIG. 13 is an explanatory diagram showing an example of the design of the cuvette portion 20F in the pattern F. Here, the dimension of each part of the cuvette part 20F is as follows.
a (incident end outer wall surface to bottom surface 143-2) = 0.5 mm
b (bottom surface 143-2 to bottom surface 123 a-2) = 0.5 mm
c (distance where the inclined surface 123a-1 is inclined) = 0.2 mm
d (distance where the inclined surface 123b-1 is inclined) = 0.2 mm
e (bottom surface 123b-2 to bottom surface 133-2) = 0.5 mm
f (distance where the inclined surface 133-1 is inclined) = 0.5 mm
g (maximum width of the opening of the notch 133) = 1.5 mm
h (width of bottom surface 143-2 and bottom surface 123a-2) = 0.5 mm
i (width of detection path 123) = 0.9 mm
j (width of bottom surface 123b-2 and bottom surface 133-2) = 0.5 mm
k (maximum width of the opening of the notch 133) = 1.9 mm
l (length of detection path: bottom surface 123a-2 to bottom surface 123b-2) = 10.0 mm
m (depth of detection path 123) = 0.9 mm
W (width of incident light incident on the outer wall surface of the incident end from the outside of the substrate) = 0.9 mm
Here, in order to obtain the effects of the present invention as described above, it is necessary that W> h and W> j.

In addition, the said dimension is an example to the last and is not limited to the said dimension.
(2-7) Other patterns In addition, the cuvette part 20A of the pattern A and the cuvette part 20D of the pattern D may be combined. The cuvette combining these includes an emission end portion having a cutout portion 33 shown in the cuvette portion 20A, and an incident end portion having a cutout portion 93 and a chamfered portion 83a shown in the cuvette portion 20D. In this case, it is possible to form a cuvette portion that exhibits the effects of the cuvette portion 20A and the cuvette portion 20D.

  Alternatively, the pattern B cuvette 20B and the pattern C cuvette 20C may be combined. The cuvette part combining these includes an emission end part having a chamfered part 43b and a notch part 53 shown in the cuvette part 20B, and an incident end part having a chamfered part 63a shown in the cuvette part 20C. In this case, it is possible to form a cuvette portion that exhibits the effects of the cuvette portion 20B and the cuvette portion 20C.

  Note that the angle obtained from the relational expressions (5) to (10) described in the patterns A to D, that is, the inclination angle for limiting the light emission area depends on the dimensions of the cuvette portions 20A to 20D. do not do. The same applies to the patterns E and F. However, in order to obtain the effect of the present invention, it is necessary that the width of the detection path is larger than the width of the bottom surface of the concave portion, and the width of the concave portion of incident light is larger than the width of the bottom surface.

(2-8) Comparison of patterns As a configuration for reliably limiting the emission area, a configuration in which a notch is provided on the outer wall surface of the emission end as in patterns A, B, E, and F is preferable. Since the emission end portion closest to the transmitted light detector is processed to limit the light emission area, the emission area can be surely limited. In particular, in the cuvette portion 20A of the pattern A, since chamfered portions are not formed at the incident end portion and the output end portion, light is not irregularly reflected by bubbles attached to the inclined surface of the chamfered portion, which is preferable. A pattern with a chamfered part is provided when the wettability of the liquid introduced into the detection path is high and bubbles are difficult to be generated, or when the generation of bubbles is suppressed by mixing a surfactant or the like. Even if it is a structure like B, E, and F, a bubble does not adhere easily to the inclined surface of a chamfer.

  In addition, the configuration of the pattern B in which the cutout portion and the chamfered portion are provided at the emission end portion can be expected to remove noise as compared with the configuration of the pattern A in which only the cutout portion is provided at the emission end portion. There is a possibility that light in the detection path is irregularly reflected by bubbles adhering to the inclined surface of the part. However, if the liquid introduced into the detection path has high wettability and bubbles are unlikely to be generated, or if the generation of bubbles is suppressed by mixing a surfactant, etc., noise can be obtained by adopting pattern B. The effect of removal can be utilized more.

  Further, the configuration of the putter D in which the cut-out portion and the chamfered portion are provided at the incident end is less likely to cause light to be diffusely reflected by the bubbles attached to the inclined surface of the chamfered portion than the configuration of the pattern C in which only the chamfered portion is provided at the incident end. Therefore, it is preferable. However, in the case of the pattern D, the distance from the device that irradiates the cuvette portion with incident light to the bottom surface of the notch becomes longer than the configuration of the pattern C by the amount of the notch. Therefore, incident light may be affected by noise due to dust or the like. Therefore, when the influence of such noise is small, by adopting the pattern D, the effect that light is hardly diffusely reflected can be further utilized.

In addition, the patterns C and D in which the chamfered portion is provided at the incident end are limited in the beam width of light traveling in the detection path by the chamfered portion than the configurations of the patterns A and B in which the chamfered portion is not present in the incident end. Therefore, it is preferable. However, since light may be irregularly reflected by bubbles on the chamfered portion, the configurations of the patterns C and D are effective when the generation of bubbles is small.
From the above, it is preferable to selectively apply the cuvette portion of each pattern according to the properties of the fluid, the measurement environment of transmitted light, and the like.

(3) Manufacturing method Next, the manufacturing method of the microchip 100 which has the said cuvette part 20 is demonstrated. The microchip 100 can be easily manufactured by using injection molding known in the art.
Each part is formed on the lower substrate 100b by injection molding, and an opening for introducing and discharging a sample from the outside of the substrate is formed on the upper substrate 100a by injection molding. Then, the microchip 100 is completed by bonding the upper substrate 100a and the lower substrate 100b together.

The injection molding is performed by preparing a mold having a shape corresponding to each part and pressing the mold against the substrate.
For example, Dianite MA521 made by Mitsubishi Rayon was used as the mold, and PET (polyethylene terephthalate) was used as the substrate. Further, PET and Mitsubishi Rayon Dyanite MA521 were dried with a hot air dryer at 150 ° C. for 5 to 10 hours for dehumidification, and injection molding was performed at a molding temperature (cylinder temperature) of 275 ° C. and a resin pressure of 15 kg / cm 2. Furthermore, thermocompression bonding is used for bonding the third substrate 25 to the first substrate 21, for example, the temperature of the metal plate to be pressed from the upper and lower sides of the substrate is set to 80 ° C., and the pressure is applied at 0.1 MPa for 3 to 5 minutes. The substrates were bonded together.

  As a substrate material, in addition to the PET substrate, PBT (polybutylene terephthalate), PMMA (polymethyl methacrylate), PC (polycarbonate), PS (polystyrene), PP (polypropylene), PE (polyethylene), PEN (polyethylene naphthalate) ), PAR (polyarylate resin), ABS (acrylic tolyl / butadiene / styrene resin), PVC (vinyl chloride resin), PMP (polymethylpentene resin), PBD (polybutadiene resin), BP (biodegradable polymer), COP (cycloolefin polymer), PDMS (polydimethylsiloxane), etc. may be used.

In addition, for bonding the substrates, an adhesive material or an adhesive may be used, or a fusion method using an ultrasonic wave or a laser method may be used.
(4) Operation of Microchip Next, a method for using the microchip and various processing procedures in the microchip will be described. FIG. 14 is an example of a flowchart showing the method of use in a microchip and the procedure of various processes in the microchip.

(A) Blood Introduction Reagents are held in advance in the reagent reservoirs 11a and 11b of the microchip 100. First, blood is introduced into the intake port 1. Next, a centrifugal force in the direction of the arrow (see FIG. 1A) is applied to the liquid in the microchip 100 by rotation about the center 1. Thereby, first, blood is introduced into the centrifuge tube 3 from the intake port 1. During the centrifugation with the center 1 and the center, the reagent held in the reagent reservoirs 11 a and 11 b is introduced into the primary mixing unit 13.

(B) Blood Cell / Plasma Separation By further rotation around the center 1, blood cells in the blood are introduced into the bottom of the holding unit 5 and plasma is separated as a supernatant (see FIG. 4B).
(C) Plasma measurement Next, centrifugal force in the direction of the arrow (see FIG. 3C) is applied by rotation about the center 2, and the plasma in the centrifuge tube 3 is introduced into the measurement unit 7. The blood cells are held in the holding unit 5 and are not introduced into the measuring unit 7. Of the plasma introduced into the measuring unit 7, an excessive amount of plasma exceeding the volume of the measuring unit 7 is discarded from the measuring unit 7 into the waste liquid reservoir 9.

(D) Primary mixing Next, centrifugal force in the direction of the arrow (see (d) in the figure) is applied by rotation about the center 1, and the plasma measured by the measuring unit 7 is introduced into the primary mixing unit 13. And the plasma and the reagent are mixed.
(E) Secondary mixing By connecting a pump to the outlet 17 and sucking, the mixed sample mixed in the primary mixing unit 13 is introduced into the secondary mixing unit 15, and the mixed sample is further mixed (see FIG. (See (e)).

(F) Colorimetric measurement Further, the mixed sample is introduced into the detection unit 20 by suction with a pump (see FIG. 5F). Then, light is transmitted through the cuvette part 20 into which the mixed sample has been introduced, and the amount of transmitted light after passing through the cuvette part 20 is measured, whereby the blood components are quantified.
In the above description, the sample and target components to be quantified are blood and blood components, but the sample introduced into the microchip is not limited to these. In addition, it is sufficient that the emission area of the light emitted from the emission end to the outside of the substrate can be limited to a desired area by the inclined surface of the cutout portion of the emission end and / or the inclined surface of the chamfered portion of the incidence end. The number of faces is not limited. For example, only a part of the surface surrounding the bottom surface may be formed with an inclined surface, or the entire surface surrounding the bottom surface may be formed with an inclined surface. Thus, as described above, the number of inclined surfaces is not limited to three, and the entire surface may be inclined.

<Second Embodiment>
(1) Overall Configuration of Microchip FIG. 15 is an overall perspective view of a microchip including a cuvette portion according to a second embodiment of the present invention.
The microchip 200 is formed of a first substrate 200a, a second substrate 200b, and a third substrate 200c that are substrates. Thus, the microchip 200 of the second embodiment is different from the first embodiment in that it is formed of three substrates. Other configurations are the same, and will be briefly described below.

  The second substrate 200b of the microchip 200 includes an inlet 201 for a sample containing a target component, a centrifuge tube 203, a holding unit 205, a measuring unit 207, a waste liquid reservoir 209, and a reagent reservoir (211a, 211b) for storing a reagent. 211, a primary mixing unit 213, a secondary mixing unit 215 including a mixer unit, an outlet 217, a cuvette unit 220 including a detection path 219, and a micro channel connecting these units. The first substrate 200a of the microchip 200 has an opening that covers one surface of the second substrate 200b and penetrates to the outside of the substrate, such as the sample inlet 201 and the outlet 217. The third substrate 200c covers the other surface of the second substrate 200b. Thus, since the third substrate 200c is formed so as to cover the other surface of the second substrate 200b, each part formed on the second substrate 200b is formed deep so as to penetrate the second substrate. May be. Therefore, when three substrates are used, each portion can be formed in the depth direction to reduce the plane area of the chip, and the microchip can be miniaturized.

(2) Various configurations of the cuvette unit The configuration of the cuvette unit 220 will be described below with various examples.
(2-1) Pattern A
(I) Configuration FIG. 16 is a perspective view showing an example of the cuvette portion of pattern A, and FIG. 17 is a cross-sectional view of the cuvette portion of pattern A in FIG. Similar to the configuration of the cuvette 20E of the pattern E of the first embodiment, the cuvette 220A of the pattern A has a notch at the exit end and a chamfer at the entrance end. Here, the cuvette portion 220A of the pattern A is the first in that the detection path is formed in the depth direction of the second substrate and the notch portion and the chamfered portion are formed in a conical shape. The rest of the configuration is the same as that of the pattern E of the embodiment E except for the cuvette portion 20E. Therefore, only a brief description will be given below.

The cuvette portion 220A is formed of a first substrate 221a, a second substrate 221b, and a third substrate 221c. The cuvette portion 220A has a detection path 223, an introduction path 225, a discharge path 227, an incident end 229 formed by a substrate at one end of the detection path 223, and an emission end formed by a substrate at the other end of the detection path 223. Part 231.
A notch 233 is formed on the outer wall of the emission end portion 231. The notch 233 has a recess formed by a bottom surface 233-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 223, and a side surface that is a conical inclined surface 233-1 surrounding the bottom surface 233-2. Is formed. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 233-2.

A chamfered portion 223 a is formed on the inner wall surface of the incident end portion 229. The chamfered portion 223a is formed so as to have a concave portion including a bottom surface 223a-2 that is substantially perpendicular to the optical axis and a side surface that is a conical inclined surface 223a-1 surrounding the bottom surface 223a-2. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 223a-2.
(Ii) Behavior of light in the cuvette portion In the cuvette portion 220A, light is emitted from the incident end portion 229 on the third substrate 221c side, and light is emitted from the emission end portion 231 on the first substrate 221a side. Since the behavior of light in the cuvette portion 220A is the same as that of the cuvette portion 20E of the pattern E in the first embodiment, description thereof is omitted.

(Iii) Example of Design FIG. 18 is an explanatory diagram showing an example of the design of the cuvette portion 220A in the pattern A. Here, the dimensions of each part of the cuvette part 220A are as follows.
a (incident end outer wall surface to bottom surface 223a-2) = 0.5 mm
b (distance where the inclined surface 223a-1 is inclined) = 0.5 mm
c (Length of detection path: bottom surface 223a-2 to inner wall surface of emission end) = 5.0 mm
d (outer end inner wall surface to bottom surface 233-2) = 0.5 mm
e (bottom surface 233-2-incident end outer wall surface) = 0.5 mm
f (width of bottom surface 223a-1 and bottom surface 233-2) = 0.5 mm
g (maximum width of opening of notch 233) = 1.6 mm
h (width of detection path 223) = 0.9 mm
W (width of incident light incident on the outer wall surface of the incident end from the outside of the substrate) = 0.7 mm
Here, in order to obtain the effect of the present invention as described above, it is necessary that W> h.

In addition, the said dimension is an example to the last and is not limited to the said dimension.
(2-2) Pattern B
(I) Configuration FIG. 19 is a perspective view illustrating an example of the cuvette portion of the pattern B, and FIG. 20 is a cross-sectional view of the cuvette portion of the pattern B in FIG. The cuvette portion 220B of the pattern B has a chamfered portion and a cutout portion at both the emission end portion and the incident end portion, similarly to the cuvette portion 20F configuration of the pattern F of the first embodiment. Here, the cuvette portion 220B of the pattern B is the first in that the detection path is formed in the depth direction of the second substrate and the notch portion and the chamfered portion are formed in a conical shape. Other configurations are the same as those of the pattern F of the embodiment F except for the configuration. Therefore, only a brief description will be given below.

The cuvette unit 220B is formed of a first substrate 241a, a second substrate 241b, and a third substrate 241c. The cuvette portion 20E includes a detection path 243, an introduction path 245, a discharge path 247, an incident end 249 formed by a substrate at one end of the detection path 243, and an emission end formed by a substrate at the other end of the detection path 243. Part 251.
A notch 263 is formed on the outer wall of the incident end of the incident end 249. The cutout portion 263 has a concave portion including a bottom surface 263-2 that is substantially perpendicular to the optical axis of the light passing through the detection path 243, and a side surface that is a conical inclined surface 263-1 surrounding the bottom surface 263-2. Is formed. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 263-2. In addition, a chamfered portion 243 a is formed on the inner wall surface of the incident end portion 249. The chamfered portion 243a is formed to have a concave portion including a bottom surface 243a-2 that is substantially perpendicular to the optical axis and a side surface that is a conical inclined surface 243a-1 surrounding the bottom surface 243a-2. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 243a-2.

  A chamfered portion 243 b is formed on the inner wall surface of the emission end portion 251. The chamfered portion 243b is formed to have a concave portion including a bottom surface 243b-2 that is substantially perpendicular to the optical axis and a side surface that is a conical inclined surface 243b-1 surrounding the bottom surface 243b-2. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 243b-2. In addition, a notch 253 is formed on the outer wall of the emission end of the emission end 251. The notch 253 is formed so as to have a recess composed of a bottom surface 253-2 that is substantially perpendicular to the optical axis and a side surface that is a conical inclined surface 253-1 that surrounds the bottom surface 253-2. The recess is formed so that the opening of the recess becomes narrower toward the bottom surface 253-2.

(Ii) Behavior of light in the cuvette part In the cuvette part 220B, light is emitted from the incident end part 249 on the third substrate 241c side, and light is emitted from the emission end part 251 on the first substrate 241a side. Since the behavior of light in the cuvette part 220B is the same as that of the cuvette part 20F of the pattern F in the first embodiment, description thereof is omitted.

(Iii) Example of Design FIG. 21 is an explanatory diagram showing an example of the design of the cuvette portion 220B in the pattern B. Here, the dimensions of each part of the cuvette part 220B are as follows.
a (incident end outer wall surface to bottom surface 263-2) = 0.5 mm
b (bottom surface 263-2 to bottom surface 243 a-2) = 0.5 mm
c (distance where the inclined surface 243a-1 is inclined) = 0.2 mm
d (distance where the inclined surface 243b-1 is inclined) = 0.2 mm
e (bottom surface 243b-2 to bottom surface 253-2) = 0.5 mm
f (distance where the inclined surface 253-1 is inclined) = 0.5 mm
g (maximum width of opening of notch 253) = 1.5 mm
h (width of bottom surface 263-2 and bottom surface 243a-2) = 0.5 mm
i (width of detection path 243) = 0.9 mm
j (width of bottom surface 243b-2 and bottom surface 253-2) = 0.5 mm
k (maximum width of opening of notch 253) = 1.9 mm
l (length of detection path: bottom surface 243a-2 to bottom surface 243b-2) = 10.0 mm
W (width of incident light incident on the outer wall surface of the incident end from the outside of the substrate) = 0.9 mm
Here, in order to obtain the effects of the present invention as described above, it is necessary that W> h and W> j.

  In addition, the said dimension is an example to the last and is not limited to the said dimension.

  The present invention relates to a clinical analysis chip, an environmental analysis chip, a gene analysis chip (DNA chip), a protein analysis chip (proteome chip), a sugar chain chip, a chromatographic chip, used in the fields of medicine, food, drug discovery, etc. It can be used for various substrates that can be applied to gases and liquids called cell analysis chips and pharmaceutical screening chips.

1 is an overall perspective view of a microchip including a cuvette portion according to a first embodiment of the present invention. (A) The perspective view of 20 A of cuvette parts of the pattern A. FIG. (B) A1-A1 'sectional view of the same figure (a). (C) A2-A2 'sectional view of the same figure (b). Explanatory drawing which shows the conditions for light to be totally reflected (A) The perspective view of the cuvette part 20B of the pattern B. FIG. (B) B1-B1 'sectional drawing of the same figure (a). (C) B2-B2 'sectional drawing of the same figure (b). (A) Explanatory drawing which shows the conditions for light to be totally reflected. (B) is an enlarged view of FIG. (A) The perspective view of the cuvette part 20C of the pattern C. FIG. (B) C1-C1 'sectional drawing of the same figure (a). (C) C2-C2 'sectional drawing of the same figure (b). Explanatory drawing which shows the conditions for light to be totally reflected. (A) The perspective view of cuvette part 20D of pattern D. FIG. (B) D1-D1 'sectional drawing of the same figure (a). (C) D2-D2 'sectional drawing of the same figure (b). Explanatory drawing which shows the conditions for light to be totally reflected. (A) The perspective view of the cuvette part 20E of the pattern E. FIG. (B) E1-E1 'sectional drawing of the same figure (a). (C) E2-E2 'sectional drawing of the same figure (b). Explanatory drawing which shows an example of the design of the cuvette part 20E in the pattern E. FIG. (A) The perspective view of the cuvette part 20F of the pattern F. FIG. (B) F1-F1 'sectional drawing of the same figure (a). (C) F2-F2 'sectional drawing of the same figure (b). Explanatory drawing which shows an example of the design of the cuvette part 20F in the pattern F. FIG. An example of the flowchart which shows the usage method in a microchip, and the procedure of the various processes in a microchip. The whole perspective view of the microchip containing the cuvette part concerning the example of a 2nd embodiment of the present invention. The perspective view which shows an example of the cuvette part of the pattern A. FIG. FIG. 17 is a cross-sectional view of the cuvette portion of pattern A in FIG. 16. Explanatory drawing which shows an example of design of cuvette part 220A in pattern A. The perspective view which shows an example of the cuvette part of the pattern B. FIG. FIG. 20 is a cross-sectional view of the cuvette portion of the pattern B in FIG. 19. Explanatory drawing which shows an example of the design of the cuvette part 220B in the pattern B. FIG.

Explanation of symbols

Intake port: 1,201
Centrifuge tube: 3, 203
Holding unit: 5, 205
Weighing section: 7,207
Waste liquid reservoir: 9, 209
Reagent reservoir: 11a, 11b, 211a, 211b
Primary mixing part: 13, 213
Secondary mixing part: 15, 215
Exit: 17, 217
Detection path: 19, 219
Cuvette part: 20A, 20B, 20C, 20E, 20F, 220A, 220B
Detection path: 23, 43, 63, 83, 103, 123, 223, 243
Incident end: 29, 49, 69, 89, 109, 129, 229, 249
Output end: 31, 51, 71, 91, 111, 131, 231, 251
Notch: 33, 53, 93, 113, 133, 143, 233, 253, 263
Chamfered portion: 43, 63a, 83a, 103a, 123a, 123b, 223a, 243a
Microchip: 100, 200

Claims (8)

A detection path formed inside the substrate and into which a sample to be quantified is introduced;
An incident end formed by a substrate at one end of the detection path, and incident light on the detection path;
Formed by a substrate at the other end of the detection path, and includes an emission end that emits light after passing through the detection path to the outside of the substrate,
In order to limit the emission area of the light emitted from the detection path, at least a notch portion of the substrate outer wall corresponding to one end of the detection path of the emission end portion and a chamfered portion of the detection path inner wall of the incident end portion One is formed,
The exit end is formed with a notch on the outer wall of the substrate corresponding to one end of the detection path, and a chamfer on the inner wall of the detection path,
The cutout portion of the emission end portion forms a recess composed of a bottom surface substantially perpendicular to the optical axis of the light passing through the detection path and a side surface including at least one inclined surface surrounding the bottom surface, The recess is formed so that the opening of the recess becomes narrower toward the bottom surface,
The chamfered portion of the emission end portion forms a recess composed of a bottom surface substantially perpendicular to the optical axis of the light passing through the detection path and a side surface including at least one inclined surface surrounding the bottom surface, Is a microchip formed such that the opening of the concave portion becomes narrower toward the bottom surface.   The cutout portion of the emission end and / or the chamfered portion of the incident end controls the light emission direction so that the light that has passed through the central portion in the cross-sectional direction of the detection path is selectively emitted. The microchip according to claim 1. The angle θ ₁ (θ ₁ <90 °) formed by the bottom surface and the inclined surface of the cutout portion of the emission end is larger than the critical angle θ _x represented by the following formula (1). Microchip

Here, n ₀ is the refractive index of the atmosphere in which the substrate is placed,
n ₁ is the refractive index of the substrate. The angle θ ₂ (θ ₂ <90 °) formed by the bottom surface and the inclined surface of the notch portion at the output end portion is the angle θ ₃ (θ ₃ <90 °) formed by the bottom surface and the inclined surface of the chamfered portion at the output end portion. The microchip according to claim 1, wherein a relationship between the microchip and the critical θ _x represented by the following formula (2) is greater:

Here, n ₀ is the refractive index of the atmosphere in which the substrate is placed,
n ₁ is the refractive index of the substrate,
n ₂ is the refractive index of the sample introduced into the detection path. A detection path formed inside the substrate and into which a sample to be quantified is introduced;
An incident end formed by a substrate at one end of the detection path, and incident light on the detection path;
Formed by a substrate at the other end of the detection path, and includes an emission end that emits light after passing through the detection path to the outside of the substrate,
In order to limit the emission area of the light emitted from the detection path, at least a notch portion of the substrate outer wall corresponding to one end of the detection path of the emission end portion and a chamfered portion of the detection path inner wall of the incident end portion One is formed,
A chamfered portion is formed on the inner wall of the detection path at the incident end,
The chamfered portion of the incident end portion forms a recess composed of a bottom surface substantially perpendicular to the optical axis of light passing through the detection path, and a side surface including at least one inclined surface surrounding the bottom surface. the opening of the recess that is formed in such a manner as to narrow as it goes to the bottom, microchip. The angle θ ₄ (θ ₄ <90 °) formed by the bottom surface of the chamfered portion of the incident end portion and the inclined surface is larger than each critical θ _x represented by the following formula (3). Microchip

Where n ₁ is the refractive index of the substrate,
n ₂ is the refractive index of the sample introduced into the detection path. The entrance end is further formed with a notch on the outer wall of the substrate corresponding to the other end of the detection path,
The cutout portion of the incident end portion forms a recess composed of a bottom surface substantially perpendicular to the optical axis of the light passing through the detection path, and a side surface including at least one inclined surface surrounding the bottom surface, The microchip according to claim 5, wherein the recess is formed so that an opening of the recess becomes narrower toward the bottom surface. The angle θ ₅ (θ ₅ <90 °) formed by the bottom surface and the inclined surface of the chamfered portion at the incident end portion is the angle θ ₆ (θ ₆ <90 °) formed by the bottom surface and the inclined surface of the notch portion at the incident end portion. ) Is larger than each critical θ _x represented by the following formula (4).

Here, n ₀ is the refractive index of the atmosphere in which the substrate is placed,
n ₁ is the refractive index of the substrate,
n ₂ is the refractive index of the sample introduced into the detection path.

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