JP2008134152A - Chemical analyzer - Google Patents

Abstract

Provided is a chemical analyzer that can reliably inject a sample and a reagent into a gap in a substrate tube and can easily discharge bubbles in the gap in the substrate tube.
A plurality of substrates arranged in parallel to each other are arranged vertically or inclined with respect to the vertical direction. The gap between the substrate tubes is filled with oil, and a sample and a reagent are injected into the oil. When the oil is heavier than the sample, reagent, and reaction product, the liquid is moved using electrowetting and gravity. In this case, a probe insertion guide is arranged at the upper end of the gap between the substrates. When the oil is lighter than the sample, reagent, and reaction product, the liquid is moved using electrowetting and buoyancy. In this case, a probe insertion guide is disposed at the lower end of the gap between the substrates.
[Selection] Figure 1

Description

  The present invention relates to a chemical analysis apparatus for analyzing a trace amount substance contained in a living body, and more particularly to a chemical analysis apparatus using droplets using dielectrophoresis or electrowetting.

  It is known that a fine particle or a droplet moves to a strong or weak electric field by an electrostatic field. This is called dielectrophoresis and is used as a technique for transporting droplets, fine particles, cells, and the like on a substrate (Non-patent Document 1). In addition, it is known that when an electric potential difference is applied between a droplet and a substrate, the apparent wettability of the droplet with respect to the substrate changes. This is called electrowetting and is used as a technique for transporting droplets along an electrode array (Patent Document 1, Patent Document 2, and Non-Patent Document 2).

  These techniques are characterized in that the volume of droplets that can be manipulated is as small as a few nanoliters to a few microliters. Therefore, if these techniques are used in a chemical analyzer that handles expensive reagents, the running cost can be reduced, and it is considered promising as an elemental technique. Further, if the amount of liquid that can be manipulated can be reduced, there is a secondary advantage that the size of the chemical analyzer can be reduced.

  As a configuration of an apparatus using such a transport technology, there are a system for transporting droplets on one substrate and a system for sandwiching droplets between two substrates and transporting the droplets between them. From the viewpoint of reducing the amount of droplets, a method using two substrates is preferable.

  There are also a horizontal type in which the substrates are arranged horizontally and a vertical type in which the substrates are arranged vertically. The vertical type has advantages such that gravity and buoyancy can be used for the movement of droplets, and that bubbles can be easily discharged.

  Further, in order to prevent evaporation of the droplets and reduce friction with the substrate, a method of filling a medium such as oil that does not mix with the droplets around the droplets is also used.

JP 2005-30987 A US Pat. No. 6565727 The Electrostatic Society, New Electrostatic Handbook, 1998, Ohmsha, Tokyo, pp.850-867. Lab on a Chip, vol.2, 2002, pp.96-101.

  As described above, in the technique of using droplets using dielectrophoresis or electrowetting, a method of moving the droplets between two vertically arranged substrates is preferable. However, a technique for injecting a sample, a reagent and the like between the substrates and a technique for discharging the waste liquid between the substrates have not been established. For example, Patent Document 2 describes the concept of introducing droplets between two substrates, but does not describe a specific method for realizing the concept.

  It is an object of the present invention to reliably inject a sample and a reagent into a gap between substrates, to easily discharge a waste liquid from the gap between substrates, to have high analysis accuracy, and high analysis throughput. It is to provide a chemical analyzer.

  According to the present invention, the plurality of substrates arranged parallel to each other are arranged vertically or inclined with respect to the vertical direction. The gap between the substrates is filled with oil. Samples and reagents are injected into this oil. Samples and reagents are moved using dielectrophoresis or electrowetting to produce reaction products. The reaction product is detected by a detector.

  By adjusting the tilt angle of the substrate, it is possible to adjust the moving speed of the droplets, bubbles, and waste liquid that move through the gaps between the substrates.

  When the oil is heavier than the sample, reagent, and reaction product, the liquid is moved using dielectrophoresis or electrowetting and gravity. In this case, a probe insertion guide is disposed at the upper end of the gap between the substrates, and the waste liquid discharge pipe is connected to the bottom of the gap between the substrates.

  When the oil is lighter than the sample, reagent, and reaction product, the liquid is moved using dielectrophoresis or electrowetting and buoyancy. In this case, a probe insertion guide is disposed at the lower end of the gap between the substrates, and a waste liquid discharge pipe is connected to the upper end of the gap between the substrates.

  According to the present invention, the sample and the reagent can be reliably injected into the gap between the substrates, the waste liquid and the bubbles can be easily discharged from the gap between the substrates, the analysis accuracy is high, and the analysis throughput is high. It is to provide a high chemical analyzer.

  With reference to FIG. 1, the example of the chemical analyzer of this invention is demonstrated. Here, a biological sample, that is, a specimen will be described as an example of an analysis target. However, the chemical analyzer of the present invention can analyze not only biological samples but also various chemical substances and pharmaceutical substances. Furthermore, although the case where a droplet is used using electrowetting is described here, the chemical analyzer of the present invention can also use a droplet using dielectrophoresis.

  The chemical analysis apparatus of the present example holds an analysis device 100 having a plurality of droplet transfer substrates 1000, an oil injection mechanism 200 for injecting oil into the analysis device 100, and a sample cup 310 containing a sample sample such as serum. A rotatable specimen disk 311, a specimen injection mechanism 300 that collects a specimen from the specimen cup 310 and injects it into the gap between the substrates, a rotatable reagent disk 411 that holds a reagent bottle 410 containing a reagent, and a reagent bottle 410 A reagent injection mechanism 400 that collects the reagent from the substrate and injects it into the gap between the substrates, an oil recovery mechanism 500 that recovers oil from the waste liquid discharged from the analysis device 100, and a controller 600 that controls these mechanisms.

  In the example of FIG. 1, the substrate 1000 is arranged vertically. However, according to the present invention, the substrate may be arranged inclined at a predetermined angle with respect to the vertical direction. Hereinafter, the drawings show a state in which the substrate is arranged along the vertical direction, but it is assumed that the substrate includes a case where the substrate is inclined at a predetermined angle with respect to the vertical direction even if not specifically described. To do.

  The oil injection mechanism 200 includes a probe 201, a tube 202 connected to the probe, a pump 203 connected to the tube, an arm 204 that supports the probe, and a probe moving mechanism 205 that moves the probe 201 in the vertical direction and the rotation direction.

  The sample injection mechanism 300 includes a probe 301, a tube 302 connected to the probe, a pump 303 connected to the tube, an arm 304 that supports the probe, and a probe moving mechanism 305 that moves the probe 301 in the vertical direction and the rotation direction.

  The sample injection mechanism 400 includes a probe 401, a tube 402 connected to the probe, a pump 403 connected to the tube, an arm 404 that supports the probe, and a probe moving mechanism 405 that moves the probe 401 in the vertical direction and the rotation direction.

  The oil recovery mechanism 500 includes a waste liquid discharge pipe 502, a waste liquid discharge valve 503, a waste liquid container 504, an oil recovery device 505, and an oil container 506 provided at the bottom of the analysis device 100.

  The analysis device 100 has an oil tank 102 that contains oil 101. In the oil tank 102, a plurality of droplet transfer substrates 1000 are arranged in parallel to each other at a predetermined interval. Spacers 103 are disposed on both sides of these substrates. The spacer 103 has a function of holding the substrate at a predetermined interval and simultaneously holding the liquid between the substrates. The lower end of the substrate is supported by a substrate support portion (not shown). The liquid is held in a space formed by the substrate, the spacer, and the substrate support portion. A waste liquid discharge pipe 502 is connected to the substrate support portion.

  The substrate 1000 is immersed in the oil 101 accommodated in the oil tank 102. The oil 101 may be any oil that does not react with the liquid between the substrates and does not mix, and is, for example, fluorine oil.

  At the upper end of the analysis device 100, a probe insertion guide 104 for guiding a probe to be inserted into the gap between the substrates is provided. On both sides of the analysis device 100, detectors 105 are provided for detecting reaction products generated in the gaps between the substrates. The detector 105 measures, for example, absorbance. The analysis device 100 is disposed on the analysis device stage 110.

  The operation of the chemical analyzer of this example will be briefly described. First, the oil tank 102 is filled with the oil 101. The arm 204 is moved by the probe moving mechanism 205, and the tip of the probe 201 is inserted into the oil tank 102. At this time, the relative position between the probe 201 and the oil tank 102 can be accurately adjusted by moving the analysis device stage 110. The pump 203 is operated, and the oil in the oil container 506 is injected into the oil tank 102 from the probe 201. Oil is also injected into the gap between the substrates. In this case, the tip of the probe 201 is inserted into the probe insertion guide 104. When the oil filling is completed, the pump 203 is stopped, the arm 204 is moved by the probe moving mechanism 205, and the probe 201 is returned to the original standby position.

  Next, the specimen to be analyzed is injected into the gap between the substrates. The sample disk 311 is rotated, and the sample cup 310 containing the sample to be analyzed is placed at the sample collection position. The arm 304 is moved by the probe moving mechanism 305, and the tip of the probe 301 is inserted into the sample cup 310 arranged at the sample collection position. The pump 303 is operated to suck the sample in the sample cup 310 from the probe 301.

  The arm 304 is moved by the probe moving mechanism 305, and the tip of the probe 301 is inserted into the probe insertion guide 104 at the upper end of the substrate. At this time, the position of the probe 301 is accurately adjusted by moving the analysis device stage 110. The analysis pump 303 is operated to inject the sample in the probe 301 into the gap between the substrates. The arm 304 is moved by the probe moving mechanism 305 to return the probe 301 to the original standby position.

  Next, the reagent is injected into the gap between the substrates. The reagent disk 411 is rotated, and the reagent bottle 410 containing a predetermined reagent is arranged at the reagent dispensing position. The arm 404 is moved by the probe moving mechanism 405, and the tip of the probe 401 is inserted into the reagent bottle 410 arranged at the reagent dispensing position. The pump 403 is operated to suck the reagent in the reagent bottle 410 from the probe 401. The arm 404 is moved by the probe moving mechanism 405, and the tip of the probe 401 is inserted into the probe insertion guide 104 disposed in the gap between the substrates into which the specimen is injected. At this time, the position of the probe 401 is accurately adjusted by moving the analysis device stage 110. The pump 403 is operated to inject the reagent in the probe 401 into the gap between the substrates. The arm 404 is moved by the probe moving mechanism 405 to return the probe 401 to the original standby position.

  The specimen and the reagent arranged in the gap between the substrates each move in the gap. The sample and reagent mix and react. The reaction product is detected by the detector 105. The detector 105 performs, for example, absorbance analysis. An output signal from the detector 105 is transmitted to a computer (not shown).

  Next, the oil recovery mechanism will be described. When the analysis in the analysis device is completed, the waste liquid discharge valve 503 is opened. The waste liquid containing the reaction product held between the substrates flows out to the waste liquid container 504 through the waste liquid discharge pipe 502. The waste liquid 501 accommodated in the waste liquid container 504 is sent to the oil recovery device 505 by a pump (not shown). The oil recovery device 505 separates waste liquid and oil. As the separation method, for example, a specific gravity difference is used. The separated oil is sent to the oil container 506 by a pump (not shown). On the other hand, the separated waste liquid is disposed of.

  A first example of the analysis device 100 of the present invention will be described with reference to FIG. In the analysis device of this example, the oil 101 having a specific gravity smaller than the specific gravity of the specimen, the reagent, and the reaction product is used.

  FIG. 2A shows a cross-sectional configuration of the analysis device 100 cut along a vertical plane orthogonal to the substrate 1000. The analysis device of this example includes an oil tank 102 and a pair of substrates 1001 and 1002. Oil 101 is filled on the outside of the substrate. Oil 101 and droplet 150 are disposed in the gap between the two substrates. That is, the periphery of the droplet 150 is held by the oil 101. The droplet 150 is a specimen, a reagent, or a reaction product. A pair of detectors 105 is provided outside the two substrates and sandwiching the two substrates. The detector 105 detects the absorbance of the droplet 150 and the like. Details of the structure and function of the detector 105 will be described later.

  A probe insertion guide 104 is attached to the upper ends of the substrates 1001 and 1002. The lower ends of the substrates 1001 and 1002 are supported by the substrate support unit 106. A tube connector 107 is attached to the substrate support portion 106. A waste liquid discharge pipe 502 is connected to the tube connector 107. A gap 108 between the substrates is connected to a waste liquid discharge pipe 502.

  The left substrate 1001 has a glass plate 1001a, an electrode 1001b formed on the inner surface thereof, an insulating film 1001c formed so as to cover the electrode, and an innermost water repellent film 1001d. The electrode 1001b is composed of an electrode array in which electrodes each having several millimeters are arranged side by side. The right substrate 1002 includes a glass plate 1002a, a common electrode 1002b formed on the inner surface thereof, and a water repellent film 1002c formed so as to cover the common electrode. The common electrode 1002b is formed so as to cover the glass plate 1002a.

  The electrode 1001b and the common electrode 1002b are in contact with contacts formed on the substrate support unit 106. The contact point of the substrate support unit 106 is connected to an external power source. By applying a voltage between one of the electrodes constituting the electrode 1001b and the common electrode 1002b, the wettability of the inner surfaces of the two substrates changes, and the droplet 150 moves.

  With reference to FIG. 2B, a method for inserting a sample into the analysis device 100 via the probe 301 will be described. FIG. 2B shows details of the upper end of the analytical device shown in FIG. 2A. A gap 108 between the two substrates 1001 and 1002 is filled with oil 101. Oil 101 is also filled outside the two substrates. The probe 301 is inserted into the probe insertion guide 104. The probe insertion guide 104 has a conical tapered opening 104a. On the other hand, the probe 301 is formed of a flexible material such as resin. When the tip of the probe 301 comes into contact with the tapered opening 104a of the probe insertion guide 104, the tip of the probe 301 is deformed along the conical surface of the tapered opening. Therefore, even if the center axis of the probe 301 does not coincide with the center axis of the probe insertion guide 104, that is, even if there is an error in the position of the probe 301, the tip of the probe 301 is connected to the probe insertion guide 104. Via, it can be surely inserted into the gap between the substrates.

  When the sample is released from the probe 301, the specific gravity of the sample is larger than the specific gravity of the oil 101, so that the sample receives a downward force due to gravity. The specimen sinks into the oil 101 and forms a droplet 150. At this time, the bubbles 151 mixed in the oil together with the specimen move upward and are released to the outside of the oil 101.

  The inner surfaces of the substrates 1001 and 1002 are covered with water-repellent films 1001d and 1002c, respectively. Since the water repellent film is hydrophobic, the contact angle of the oil 101 with respect to the water repellent films 1001d and 1002c is very small, or the oil 101 can completely spread on the water repellent film. Therefore, the adhesion force of the bubbles 151 to the water repellent film is sufficiently smaller than the buoyancy, and the bubbles 151 are surely discharged by the buoyancy.

  The same applies when a reagent is injected into the gap 108 between the substrates. A reagent droplet 150 is generated.

  Next, a method for moving droplets in the gap between the substrates will be described. In this example, the specific gravity of the droplet 150 is greater than the specific gravity of the oil. Accordingly, a downward force corresponding to the difference between gravity and buoyancy acts on the droplet 150. Thereby, the droplet 150 descends in the gap between the substrates. Since the downward force acting on the droplet is small and the viscosity of the oil is sufficiently large, the droplet 150 descends slowly. On the other hand, when a voltage is applied between one electrode of the left substrate and the common electrode of the right substrate, the droplet is attracted to the electrode of the left substrate by electrostatic force. When the electrostatic force acting on the droplet overcomes the downward force, the droplet is held by the electrostatic force. In this way, the droplet can be moved in the gap between the substrates by utilizing the gravity and electrostatic force acting on the droplet 150.

  According to the present invention, the downward force caused by gravity acting on the droplet is reduced by tilting the substrate at a predetermined angle with respect to the vertical direction. When the substrate is tilted, the droplets move along the substrate. Therefore, the path along which the droplet moves is not the vertical direction but the maximum tilt direction of the substrate. At this time, the downward force acting on the droplet is in a direction along the droplet path. This force is less than the value of gravity. By changing the tilt angle of the substrate, the downward moving force acting on the droplet can be adjusted.

  As described above, the electrode 1001b of the left substrate 1001 is composed of a plurality of electrodes arranged in a line. Initially, an electrode is applied between the first electrode and the common electrode. The droplet 150 is held by the first electrode. The voltage applied to the first electrode is cut off, and a voltage is applied between the second electrode and the common voltage. Thereby, the droplet moves from the position of the first electrode to the position of the second electrode. By repeating such an operation, the droplet can be moved along the electrode example.

  Not only when the electrode rows are arranged along the vertical direction, but also when the electrode rows are arranged along the horizontal direction, the droplets can be moved along the electrode rows.

  A reaction part is provided in the electrode array. The reaction part is an electrode provided at a position crossing the optical path of the detector 105. First, the specimen is moved to the reaction unit, and then the reagent is moved to the reaction unit. In the reaction unit, the specimen and the reagent are mixed to generate a reaction product. In order to promote mixing of the specimen and the reagent, the mixture may be reciprocated along a predetermined electrode array. When the reaction in the reaction section has sufficiently progressed, the reaction product is detected by the detector 105. For example, the detector 105 may include a light emitting device provided on one side of the substrate and a light receiving device provided on the opposite side of the substrate. Light of a predetermined wavelength from the light emitting device passes through the reaction product generated in the reaction part and is detected by the light receiving device. Absorbance is detected from the detection signal detected by the light receiving device.

  When the analysis of the reaction product is completed, the voltage applied to all the electrodes is cut off. The reaction product falls through the oil and accumulates at the bottom of the analytical device.

  A method for discharging the waste liquid 501 from the bottom of the analysis device will be described with reference to FIG. 2C. FIG. 2C shows details of the lower end of the analytical device shown in FIG. 2A.

  The inner surface of the lower part of the spacer 103 is tapered. A tube connector 107 is provided at the lower end of the spacer 103. A waste liquid discharge pipe 502 is attached to the tube connector 107. In the waste liquid discharge pipe 502, the tip of the waste liquid discharge pipe 502 provided with the waste liquid discharge valve 503 is connected to the waste liquid container 504.

  The waste liquid 501 is accumulated in the tapered portion below the spacer 103. When the waste liquid discharge valve 503 is opened, the waste liquid 501 falls through the waste liquid discharge pipe 502 due to a water head difference and is discharged to the waste liquid container 504.

Next, a method for manufacturing the substrates 1001 and 1002 is described. First, a method for manufacturing the left substrate 1001 will be described. First, a glass plate is prepared, and a transparent conductive film such as ITO is formed on the surface thereof. An insulating substrate such as a quartz plate may be used instead of the glass plate. A method for forming the transparent conductive film is a vacuum deposition method, a sputtering method, a CVD method, or the like. Next, an organic insulating film such as parylene (trade name, Three Bond Co.) or an inorganic insulating film such as SiO ₂ is formed so as to cover the surface on which the electrode is formed. The insulating film forming method is a vacuum deposition method, a sputtering method, a CVD method, or the like. Next, a water repellent film made of Teflon AF1600 (trade name, DuPont), Cytop (trade name, Asahi Glass Co., Ltd.) or the like is formed on the insulating film. The water repellent film is formed by a dip coating method, a spin coating method, or the like.

  Next, a method for manufacturing the right electrode 1002 will be described. First, an insulating substrate such as a glass plate or a quartz plate is prepared, and a transparent conductive film such as ITO is formed so as to cover the surface. The method for forming the transparent conductive film is the same as that for the left substrate 1001. However, in the case of the right electrode 1002, the common electrode is formed over the entire surface. Next, a water repellent film is formed. The method for forming the water repellent film is the same as that for the left substrate 1001.

  A second example of the analysis device according to the present invention will be described with reference to FIG. In the analysis device of this example, the oil 101 having a specific gravity smaller than the specific gravity of the specimen, the reagent, and the reaction product is used. FIG. 3 shows a cross-sectional configuration obtained by cutting the analysis device 100 of this example along a vertical plane orthogonal to the substrate 1000. In this example, a plurality of substrates are arranged in the oil tank 102. Out of these substrates, the two outer substrates 1001 and 1002 are the same as the substrates 1001 and 1002 used in the analysis device of FIG. 2A. Among these substrates, the inner substrates 1003, 1004, and 1005 are different from the outer substrates 1001 and 1002. Each of these substrates 1003, 1004, and 1005 has a structure in which two substrates 1001 and 1002 used in the analysis device of FIG. 2A are bonded together. For example, the substrate 1005 includes a glass substrate 1005a, a common electrode 1005b formed on one surface thereof, a water repellent film 1005c formed so as to cover the common electrode, and an electrode formed on the other surface of the glass substrate. 1005d, an insulating film 1005e formed to cover the electrode 1005d, and a water repellent film 1005f formed to cover the insulating film. The analysis device of this example is different from the example of FIG. 2 in that three or more substrates are used, and the other structure is the same as that of the example of FIG.

  A third example of the analysis device according to the present invention will be described with reference to FIG. In the analysis device of this example, the oil 101 having a specific gravity larger than the specific gravity of the specimen, the reagent, and the reaction product is used. FIG. 4 is a diagram showing a cross-sectional configuration of the analysis device of this example cut along a vertical plane parallel to the substrate 1000.

  The analysis device of this example includes an oil tank 102 and a plurality of substrates 1000. The substrate 1000 may include a pair of substrates as illustrated in FIG. 2, but may include a plurality of substrates as illustrated in FIG. 3. The oil tank 102 is filled with oil 101. In this example, the tip 301b of the probe 301a is formed in an L shape. A probe insertion guide 104 a is provided near the lower end of the substrate 1000. A tube connector 107 a is provided at a position slightly below the surface of the oil disposed in the oil tank 102 so as to penetrate the wall surface of the oil tank 102. A waste liquid discharge pipe 502 is connected to the tube connector 107a. The upper part of the oil stored in the oil tank 102 is connected to a waste liquid discharge pipe 502. Further, a waste liquid guide 160 is provided near the upper end of the substrate 1000. The waste liquid guide 160 has an inclined surface coated with a water repellent film.

  The tip 301b of the probe 301a is inserted into the probe insertion guide 104a, and the specimen is injected from the probe 301a into the gap between the substrates. At this time, air is mixed into the oil simultaneously with the specimen. The bubbles 151 rise in the oil, move along the waste liquid guide 160, and are released from the oil into the air. Similarly, the reagent is injected into the gap between the substrates.

  Next, a method of moving droplets such as specimens and reagents in the gap between the substrates will be described. In this example, the specific gravity of the droplet 150 is smaller than the specific gravity of oil. Accordingly, an upward force corresponding to the difference between buoyancy and gravity acts on the droplet 150. As a result, the droplet 150 rises in the gap between the substrates. Since the upward force acting on the droplet is small and the viscosity of the oil is sufficiently large, the droplet 150 rises slowly. On the other hand, when a voltage is applied between one electrode of the left substrate and the common electrode of the right substrate, the droplet is attracted to the electrode of the left substrate by electrostatic force. When the electrostatic force acting on the droplet overcomes the upward force, the droplet is held by the electrostatic force. In this way, the buoyancy and electrostatic force acting on the droplet 150 can be used to move the droplet in the gap between the substrates.

  The method of moving the droplet along the electrode array and the method of detecting the reaction product by the detector 105 are the same as in the example of FIG. 2A.

  When the analysis of the reaction product is completed, the voltage applied to all the electrodes is cut off. The waste liquid 501 containing the reaction product rises in the oil and reaches the waste liquid guide 160. The waste liquid 501 moves along the lower inclined surface of the waste liquid guide 160 and is guided near the wall surface of the oil tank 102. Waste liquid 501 accumulated in the vicinity of the wall surface of the oil tank 102 is discharged through a waste liquid discharge pipe 502.

  The configuration of the detector 105 will be described with reference to FIGS. Here, a case where the reaction product is analyzed by measuring absorbance will be described. The detector 105 includes a light emitting unit 105a and a light receiving unit 105b.

  A first example of the detector will be described with reference to FIG. FIG. 5A is a perspective view showing five substrates 1001 to 1005 taken out from the oil tank 102, and FIG. 5B is a top view thereof. The detector of this example includes four light emitting units 105a and four light receiving units 105b. Four gaps are formed by the five substrates. Four light emitting portions 105a are provided on one side of the four gaps, and four light receiving portions 105b are provided on the opposite side. That is, the light emitting unit 105a and the light receiving unit 105b are provided in each gap.

  As shown in FIG. 5B, the light 105 c from the light emitting unit 105 a reaches the droplet 150 made of the reaction product via the transparent spacer 103 and the oil 101. The light transmitted through the droplet 150 reaches the light receiving unit 105 b via the oil 101 and the spacer 103. The light receiving unit 105b measures the absorbance, for example.

  A second example of the detector will be described with reference to FIG. 6A is a perspective view showing five substrates 1001 to 1005 taken out from the oil tank 102, and FIG. 6B is a top view thereof. In this example, the detector of this example includes one light emitting unit 105a, a light emitting unit moving mechanism 105A, one light receiving unit 105b, and a light receiving unit moving mechanism 105B. Four gaps are formed by the five substrates. A light emitting unit 105a and a light emitting unit moving mechanism 105A are provided on one side of these gaps, and a light receiving unit 105b and a light receiving unit moving mechanism 105B are provided on the opposite side. In this example, only one light emitting unit 105a and one light receiving unit 105b are provided, but each can be moved by a moving mechanism. The light emitting unit 105a can be disposed in front of an arbitrary gap by the light emitting unit moving mechanism 105A. Similarly, the light receiving unit 105b can be arranged in front of an arbitrary gap by the light receiving unit moving mechanism 105B.

  As shown in FIG. 6B, the light emitting unit 105a and the light receiving unit 105b are arranged on both sides of the same gap. In this way, by moving the light emitting unit 105a and the light receiving unit 105b by the moving mechanism, it is possible to sequentially measure the droplets arranged in the gap.

  Another example of the analysis device will be described with reference to FIG. FIG. 7 is a top view of the five substrates 1001 to 1005 taken out from the oil tank 102, as in FIGS. 5B and 6B. As shown in the figure, in this example, a transparent droplet shaping member 155 is provided so as to sandwich the droplet 150 in the gap between the substrates. In the example shown in FIGS. 5B and 6B, since the droplet 150 is held by the oil 101, the free surface is curved by the surface tension. Therefore, part of the light from the light emitting unit 105a is reflected or scattered by the surface of the curved droplet. Therefore, the light received by the light receiving unit 105b is reduced.

  In this example, the droplet 150 is held between the droplet shaping members 155. Therefore, the surface of the droplet on which the light from the light emitting unit 105a is incident is a flat surface and perpendicular to the incident light. Therefore, the light from the light emitting unit 105a is not reflected or scattered on the incident surface of the droplet, and all the light passes through the droplet.

  A third example of the detector will be described with reference to FIG. FIG. 8A is a perspective view showing five substrates 1001 to 1005 taken out from the oil tank 102, and FIG. 8B is a bottom view thereof. As shown in the figure, in this example, the substrate is composed of a rectangular portion and a protruding portion protruding downward. These projections form gaps between the projections of adjacent substrates, and droplets 150 as reaction products are arranged in the gaps between these projections.

  As shown in FIG. 8B, the gap between the protrusion 1001A of the first substrate 1001 and the protrusion 1002A of the second substrate 1002, the protrusion 1002A of the second substrate 1002, and the protrusion 1003A of the third substrate 1003. , A gap between the protrusion 1003A of the third substrate 1003 and the protrusion 1004A of the fourth substrate 1004, and a protrusion 1005A of the protrusion 1004A of the fourth substrate 1004 and the fifth substrate 1005. Droplets 150 are arranged in the gaps between the two. Although the dimensions of the protrusion 1001A of the first substrate 1001 and the protrusion 1005A of the fifth substrate 1005 are relatively small, the dimensions of the protrusions 1002A, 1003A, and 1004A of the second, third, and fourth substrates are as follows. Relatively small. In this example, four gaps are formed by the protrusions of the five substrates. Accordingly, four droplets 150 are respectively arranged in the four gaps. These droplets 150 are displaced along a direction parallel to the substrate so as not to overlap each other.

  A light emitting unit 105a and a light receiving unit 105b are disposed on both sides of the droplet 150, respectively. The light emitting unit 105a and the light receiving unit 105b are disposed on the protruding portion of the substrate. Therefore, the optical axes of these detectors are arranged at regular intervals and perpendicular to the substrate. The light from the light emitting unit 105a passes through the transparent substrate, passes through the droplet 150, passes through the transparent substrate again, and is received by the light receiving unit 105b.

  When the example of FIG. 6 is compared with this example, in the example of FIG. 6, the optical axis of the detector is arranged in parallel to the substrate, but in this example, the optical axis of the detector is orthogonal to the substrate. Is arranged. In the example of FIG. 6, the distance between the light emitting unit 105a and the light receiving unit 105b is equal to the dimension of one side of the substrate, but in this example, the distance between the light emitting unit 105a and the light receiving unit 105b is the distance between the two substrates. Equal to the distance between the outer surfaces. That is, in this example, the distance between the light emitting unit 105a and the light receiving unit 105b is short. In the example of FIG. 6, the light from the light emitting unit 105a is incident on the free surface of the droplet and is emitted from the free surface of the droplet on the opposite side. That is, the light incident surface and light exit surface from the light emitting unit 105a are free surfaces curved by surface tension. On the other hand, in this example, the light incident surface and light exit surface from the light emitting unit 105a are flat surfaces in contact with the transparent substrate. Accordingly, scattering or reflection of light at the entrance surface and the exit surface is avoided.

  Although the example of the present invention has been described above, the present invention is not limited to the above-described example, and it is easy for those skilled in the art that various modifications can be made within the scope of the invention described in the claims. Will be understood.

It is a figure which shows the whole structure of the chemical analyzer of this invention. It is a figure which shows the structure of the 1st example of the analysis device of this invention. It is a figure which shows the structure of the 2nd example of the analytical device of this invention. It is a figure which shows the structure of the 3rd example of the analytical device of this invention. It is a figure which shows the structure of the 1st example of the board | substrate and detector of an analysis device of this invention. It is a figure which shows the structure of the 2nd example of the board | substrate and detector of an analysis device of this invention. It is a figure which shows the structure of the 3rd example of the board | substrate and detector of the analysis device of this invention. It is a figure which shows the structure of the 4th example of the board | substrate and detector of an analysis device of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 ... Analytical device 101 ... Oil, 102 ... Oil tank, 103 ... Spacer, 104 ... Probe insertion guide, 105 ... Detector, 105a ... Light emitting part, 105b ... Light receiving part, 106 ... Substrate support part, 107 ... Tube connector , 108 ... gap, 110 ... stage for analysis device, 150 ... droplet, 151 ... bubble, 155 ... droplet shaping member, 160 ... waste liquid guide, 200 ... oil injection mechanism, 201 ... probe, 202 ... tube, 203 ... pump , 204 ... arm, 205 ... probe moving mechanism, 300 ... sample injection mechanism, 301 ... probe, 302 ... tube, 303 ... pump, 304 ... arm, 305 ... probe moving mechanism, 310 ... sample cup, 311 ... sample disk, 400 ... Sample injection mechanism, 401 ... Probe, 402 ... Tube, 403 ... Pump 404 ... arm, 405 ... probe moving mechanism, 410 ... reagent bottle, 411 ... reagent disk, 500 ... oil recovery mechanism, 501 ... waste liquid, 502 ... waste liquid discharge pipe, 503 ... waste liquid discharge valve, 504 ... waste liquid container, 505 ... oil Recovery device, 506 ... oil container, 600 ... controller

Claims (20)

A plurality of substrates arranged in parallel to each other and a detector for detecting a reaction product generated in the gap between the substrates, and droplets in the gap between the substrates by dielectrophoresis or electrowetting An analysis device configured to move the sample, a sample injection mechanism including a probe for injecting a sample into the gap between the substrates, a reagent injection mechanism including a probe for injecting a reagent into the gap between the substrates, In a chemical analyzer having
The analysis device includes a spacer for holding the substrates at a constant interval, a substrate support for holding the lower end of the substrate, and a probe insertion for guiding a probe inserted into the gap between the substrates. And a waste liquid discharge pipe connected to the gap between the substrates, the gap between the substrates surrounded by the spacer and the substrate support is filled with oil, and the probe insertion guide is And the sample and the reagent are introduced into the oil in the gap between the substrates, and the waste liquid in the oil in the gap between the substrates is discharged through the waste liquid discharge pipe.   2. The chemical analyzer according to claim 1, wherein the substrate is inclined at a predetermined inclination angle with respect to a vertical direction.   The chemical analyzer according to claim 1, further comprising an oil tank for storing oil, wherein the substrate is immersed in the oil in the oil tank. The chemical analyzer according to claim 1,
The substrate includes first and second substrates facing each other, and an electrode array including a plurality of electrodes is provided on one surface of the two surfaces facing each other of the first and second substrates. A common electrode is provided on the other surface;
By applying a voltage between one electrode of the electrode array and the common electrode, the droplet is moved in the gap between the first and second substrates. Chemical analysis equipment.   5. The chemical analyzer according to claim 4, wherein a water repellent film is provided so as to cover the electrode array and the common electrode.   2. The chemical analyzer according to claim 1, wherein the oil has a specific gravity greater than that of the sample, the reagent, and the reaction product.   7. The chemical analyzer according to claim 6, wherein the probe insertion guide is disposed at an upper end between the substrates.   7. The chemical analysis apparatus according to claim 6, wherein the waste liquid discharge pipe is disposed at a lower end between the substrates.   2. The chemical analyzer according to claim 1, wherein the oil has a specific gravity smaller than that of the sample, the reagent, and the reaction product.   10. The chemical analyzer according to claim 9, wherein the probe insertion guide is disposed at a lower end between the substrates.   10. The chemical analyzer according to claim 9, wherein the waste liquid discharge pipe is arranged at an upper end of a gap between the substrates. A plurality of substrates arranged in parallel to each other, an electrode formed on the substrate, oil filled in a gap between the substrates, and a voltage applied to the electrodes in the oil in the gap between the substrates. In an analytical device configured to move an introduced sample, a reagent and a reaction product of the sample and the reagent by dielectrophoresis or electrowetting,
A detector for detecting the reaction product generated by the oil in the gap between the substrates is provided, the detector having a light emitting part for emitting light and a light receiving part for receiving light, and the light emitting part The analysis device is characterized in that the light from the light passes through the reaction product disposed in the gap between the substrates and is received by the light receiving unit.   13. The analysis device according to claim 12, wherein a light path from the light emitting unit to the light receiving unit is orthogonal to the substrate, and light from the light emitting unit is transmitted through the substrate and disposed in a gap between the substrates. An analysis device characterized in that it passes through the reaction product, passes through the substrate, and is received by the light receiving section.   The analysis device according to claim 13, wherein the substrate comprises a pair of substrates arranged in parallel to each other.   14. The analysis device according to claim 13, wherein the substrate includes at least three substrates, and each of the substrates has a rectangular portion and a protruding portion protruding from the rectangular portion, and the protruding portion includes a protruding portion of an adjacent substrate. The reaction products are arranged for each gap between the overlapping projections of adjacent substrates, and the light emitting unit and the light receiving unit are arranged for each reaction product. The light passes through the protrusions of the substrate, passes through the reaction product disposed in the gap between the protrusions of the substrate, passes through the protrusions of the substrate, and is received by the light receiving portion. Analytical device.   16. The analysis device according to claim 15, wherein the reaction products are arranged at predetermined equal intervals, and light paths from the light emitting unit to the light receiving unit are arranged at predetermined equal intervals. Analytical device.   13. The analytical device according to claim 12, wherein a light path from the light emitting unit to the light receiving unit is parallel to the substrate, and the light from the light emitting unit is a reaction product arranged in a gap between the substrates. An analysis device that transmits an object and is received by the light receiving unit.   18. The analysis device according to claim 17, wherein the light emitting unit and the light receiving unit are provided for each gap between the substrates.   18. The analysis device according to claim 17, wherein the light emitting unit and the light receiving unit can be moved by a moving mechanism and can be arranged in a gap between substrates on which a reaction product to be measured is arranged. An analysis device characterized in that it is configured.   18. The analysis device according to claim 17, wherein a droplet shaping member is provided in a gap between the substrates so as to sandwich the droplet.

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