JP2009042148A - Micro inspection chip and inspection apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a micro inspection chip and inspection apparatus that efficiently mix a plurality of kinds of liquids and make them react with each other, can detect a target material from the produced liquid obtained by the reaction, and are suitable for miniaturization or cost reduction. <P>SOLUTION: Mixture of the plurality of kinds of liquids is made to flow into an amplification section from the tip of a projection projecting like a beak into the amplification section, thereby efficiently mixing the plurality of kinds of liquids. The surface of the mixture is prevented from coming into contact with a wall surface of the amplification part, thereby efficiently mixing the plurality of kinds of liquids. The reaction is amplified by heating in the amplification section to obtain the produced liquid and the target material in the produced liquid is detected in the amplification section, so that the micro inspection chip and inspection apparatus can be provided that can make the plurality of kinds of liquids efficiently react with each other, can detect the target material from the obtained produced liquid, and are suitable for miniaturization or cost reduction. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a micro test chip and a test apparatus, and more particularly to biological substance inspection / analysis by gene amplification reaction, antigen-antibody reaction, etc., inspection / analysis of other chemical substances, chemical synthesis of target compounds by organic synthesis, etc. The present invention relates to a micro inspection chip and an inspection apparatus used.

  In recent years, by making full use of micromachine technology and ultrafine processing technology, devices and means (for example, pumps, valves, flow paths, sensors, etc.) for performing conventional sample preparation, chemical analysis, chemical synthesis, etc. have been miniaturized. An analysis chip integrated on the chip has been developed (see, for example, Patent Document 1).

  This is also called μ-TAS (Micro Total Analysis System), bioreactor, Lab-on-chip, biochip, and it is used in the medical examination / diagnosis field, environmental measurement field, and agricultural production field. Application is expected. In particular, when complicated processes, skilled techniques, and equipment operations are required as seen in genetic testing, an analytical chip with excellent automation, high speed, and simplification is cost-effective and requires a small amount of sample. Because it enables analysis not only for the required time but also for any time and place, the benefits are great.

  In various types of analysis and inspection, importance is attached to the quantitativeness of analysis, the accuracy of analysis, and the economy of these analysis chips. For that purpose, it is a problem to establish a highly reliable liquid feeding system with a simple configuration, and there is a demand for a microfluidic control element having high accuracy and excellent reliability. The inventors of the present invention have already proposed a micropump system suitable for this and a control method thereof (for example, see Patent Documents 2 to 4).

  In the analysis chip as described above (hereinafter referred to as a micro test chip), it is desirable that a mixed reagent obtained by mixing a plurality of reagents and a sample can be reacted. Therefore, in the micro test chip, various mixing operations such as mixing of reagents and mixing of a reagent and a sample are required in one chip. In view of this, a method has been proposed in which two types of liquids are mixed from two liquid reservoirs through a Y-shaped channel and mixed into a long mixing channel, and the target substance is detected in the detection unit (for example, , See Patent Document 5).

In addition, the mixture of the reagent and sample is poured into the reaction chamber and reacted by circulating temperature in the reaction chamber, and then sent to the detection chamber and the presence of the target substance through the window provided in the detection chamber. A method of performing a test has been proposed (see, for example, Patent Document 6).
JP 2004-28589 A JP 2001-322099 A JP 2004-108285 A JP 2004-270537 A US Pat. No. 6,743,399 Japanese Patent No. 3558294

  However, in the method proposed in Patent Document 5, the two types of liquids that flow into the mixing channel via the Y-shaped channel do not mix easily because they flow in a laminar flow in the mixing channel. Therefore, it is not mixed unless the length of the mixing channel is very long. For this reason, the mixing channel occupies a large area on the micro test chip, which is an obstacle to miniaturization and cost reduction of the micro test chip. Moreover, since it is necessary to send the liquid over a long distance, the load on the liquid-feeding micropump is also large.

  Further, even in the method proposed in Patent Document 6, since the reaction chamber and the detection chamber are separately provided, a large space is required on the micro inspection chip, which becomes an obstacle to downsizing and cost reduction of the micro inspection chip. .

  The present invention has been made in view of the above circumstances, and can mix and react a plurality of types of liquids efficiently, detect a target substance from a product liquid obtained by the reaction, and reduce the size and cost. It is an object to provide a suitable micro inspection chip and inspection apparatus.

  The object of the present invention can be achieved by the following constitution.

1. A liquid mixture flow path for sending a liquid mixture of a plurality of types of liquids downstream;
In a micro test chip including an amplification unit that communicates with the downstream of the mixed liquid channel and amplifies a reaction of the mixed liquid by heating to obtain a product liquid.
The communication part between the mixed liquid channel and the amplification part is a narrow channel whose channel width is narrower than the mixed liquid channel,
The micro-inspection chip, wherein the most downstream portion of the narrow channel opens at a tip portion of a protruding portion protruding in a beak shape from an inner wall of the amplification unit.

  2. 2. The micro test chip according to 1, wherein the amplification unit has a gap between a side surface and an upper surface of an inner wall of the amplification unit and the mixed solution even when the entire amount of the mixed solution is fed.

  3. 3. The micro test chip according to 1 or 2, wherein an inner wall of the amplification unit is hydrophobic.

  4). 4. The micro test chip according to claim 1, wherein the amplification unit has a detection region for detecting a target substance contained in the product solution.

  5). The micro test chip according to any one of 1 to 4, further comprising a plurality of liquid storage portions that quantitate and store a plurality of the liquids upstream of the mixed liquid channel.

6.1 to 5 micro inspection chip according to any one of,
A micropump for feeding the liquid mixture;
A heating unit for heating the mixed solution;
An inspection apparatus comprising: a detection unit that detects a target substance contained in the product liquid.

  According to the present invention, it is possible to efficiently mix a plurality of types of liquids by allowing a mixture of a plurality of types of liquid to flow into the amplifying unit from the tip of the protrusion protruding into the amplifying unit. Moreover, a plurality of types of liquids can be mixed efficiently by preventing the surface of the mixed liquid from coming into contact with the wall surface of the amplification unit. Furthermore, the reaction is amplified by heating in the amplification unit to obtain a product solution, and the target substance in the living liquid is detected in the amplification unit, so that multiple types of liquids can be reacted efficiently and the target product can be obtained from the resulting product solution. A substance can be detected, and a micro inspection chip and an inspection apparatus suitable for downsizing and cost reduction can be provided.

  Hereinafter, the present invention will be described based on the illustrated embodiment, but the present invention is not limited to the embodiment. In the drawings, the same or equivalent parts are denoted by the same reference numerals, and redundant description is omitted.

  First, an inspection apparatus according to the present invention will be described with reference to FIG. FIG. 1 is a schematic diagram showing an example of an inspection apparatus according to the present invention.

  In FIG. 1, the inspection apparatus 1 includes a micro inspection chip 100, a micro pump unit 210, a heating / cooling unit 230, a detection unit 250, a drive control unit 270, and the like. The micro pump unit 210 performs liquid feeding in the micro test chip 100. The heating / cooling unit 230 heats and cools a specimen, a reagent, a mixed solution thereof, and the like in order to promote and suppress a reaction in the micro test chip 100. The detection unit 250 detects a target substance contained in a product solution obtained by a reaction in the micro test chip 100. The drive control unit 270 performs driving, control, detection, and the like of each unit in the inspection apparatus 1.

  The micropump unit 210 includes a micropump 211, a chip connection unit 213, a driving liquid tank 215, a driving liquid supply unit 217, and the like. The micro pump 211 feeds the driving liquid 216. The chip connection unit 213 connects the micropump 211 and the micro inspection chip 100. The driving liquid tank 215 supplies a driving liquid 216 for liquid feeding. The driving liquid supply unit 217 supplies the driving liquid 216 from the driving liquid tank 215 to the micropump 211. The driving liquid tank 215 can be removed and replaced from the driving liquid supply unit 217 to replenish the driving liquid 216. One or a plurality of pumps are formed on the micropump 211, and the plurality of pumps can be driven independently or in conjunction with each other.

  The heating / cooling unit 230 includes a cooling unit 231 and a heating unit 233. The cooling unit 231 includes a Peltier element or the like. The heating unit 233 includes a heater or the like. Of course, the heating unit 233 may also be formed of a Peltier element. The detection unit 250 includes a light source 251 such as a light emitting diode (LED) or a laser, a light receiving element 253 such as a photodiode (PD), and the like, and a target substance contained in a generated liquid obtained by a reaction in the micro inspection chip 100. Is detected optically at the position of the detection region 255 on the micro inspection chip 100.

  The micro inspection chip 100 is equivalent to what is generally called an analysis chip, a microreactor chip, and the like. For example, the micro inspection chip 100 is made of resin, glass, silicon, ceramics, and the like. Is formed with a fine flow path having a level of several μm to several hundred μm. The size and shape of the micro inspection chip 100 is usually a plate shape having a length and width of several tens of mm and a thickness of several mm.

  The micro test chip 100 and the micro pump 211 are connected to and communicated with each other through a chip connection unit 213, and the micro pump 211 is driven to drive various reagents and samples stored in a plurality of storage units in the micro test chip 100. However, the liquid is fed by the driving liquid 216 flowing into the micro test chip 100 from the micro pump 211 via the chip connection part 213.

  Next, the configuration of the main part of the micro test chip 100 according to the present invention will be described with reference to FIG. FIG. 2 is a schematic diagram showing a configuration of a main part of the micro inspection chip 100 according to the present invention. Here, the case where the plurality of types of liquids in the present invention are one type of reagent and one type of sample is illustrated, but the present invention is not limited thereto, and may be a reagent and a reagent or a plurality of types of reagent and a sample.

  In FIG. 2, the micro test chip 100 includes flow paths such as a reagent storage part 121, a specimen storage part 131, a mixed liquid flow path 141, an amplification part 111, and an exhaust valve 151. Each flow path is preferably made of a hydrophobic material such as plastic, or made hydrophobic by applying a hydrophobic coating to the inner surface of the flow path.

  The reagent storage unit 121 is provided with water repellent valves 125a and 125b on the upstream side and the downstream side, respectively. In addition, a reagent inlet 127 is provided in the reagent reservoir 121. By injecting an appropriate amount of the reagent 123 from the reagent injection port 127, the reagent 123 is quantified from the water repellent valves 125a to 125b and fully filled. After completion of filling of the reagent 123, the reagent inlet 127 is sealed with a sealing member 129 made of an adhesive sheet or the like.

  Similarly, in the sample reservoir 131, the sample 133 is quantified from the water-repellent valves 135a to 135b and is fully filled by injecting an appropriate amount of the sample 133 from the sample inlet 137. After completion of the filling of the specimen 133, the specimen injection port 137 is sealed with a sealing member 139 made of an adhesive sheet or the like.

  The reagent 123 and the sample 133 stored in the reagent storage unit 121 and the sample storage unit 131 are moved downstream by the driving liquid 216 sent from the micropump 211 located upstream of the reagent storage unit 121 and the sample storage unit 131. The liquid is sent. The reagent reservoir 121 and the specimen reservoir 131 function as a plurality of liquid reservoirs in the present invention.

  FIG. 2 shows a state in which the reagent 123 and the specimen 133 are fed halfway through the mixed liquid channel 141. Since the reagent 123 and the specimen 133 are sent as a laminar flow, they are not so mixed in the mixed liquid channel 141. Thereafter, the reagent 123 and the specimen 133 are sent from the mixed solution channel 141 to the amplification unit 111, mixed and heated in the amplification unit 111, and the reaction is promoted to become a product solution.

  A narrow channel 113 communicates downstream of the mixed solution channel 141, and the tip of the narrow channel 113 opens to the tip of the projection 115 protruding from the inner wall 111 a of the amplifier 111 into the inside of the amplifier 111. is doing. The reagent 123 and the specimen 133 flow from the mixed solution channel 141 through the narrow channel 113 into the amplification unit 111 from the tip of the projection 115.

  Next, an embodiment of the present invention will be described with reference to FIGS. FIG. 3 is a schematic diagram showing the configuration of the main flow path of the embodiment of the present invention centering on the amplifying unit 111, and FIG. 3A shows the surface on which the flow path of the micro test chip 100 is formed ( FIG. 3B is a view showing the AA ′ cross section of FIG. 3A with the flow path face down. For convenience of description with reference to cross-sectional views, the view from the flow path surface side of FIG. 3 and subsequent figures shows that the portion downstream from the mixed liquid flow path 141 in FIG. It is shown with a degree of rotation.

  In FIG. 3A, as described above, the protrusion 115 protruded from the inner wall 111 a of the amplifying unit 111 into the inside of the amplifying unit 111 at the tip of the narrow channel 113 communicating with the downstream of the mixed liquid channel 141. Open at the tip of the. The amplifying unit 111 has a substantially quadrangular shape with rounded corners, and an exhaust valve 151 is provided on the wall surface 111 b facing the protruding portion 115.

  Near the center of the amplification unit 111, a detection region 255 for optically detecting a target substance contained in a product solution obtained by the reaction in the amplification unit 111 is provided. At least a portion of the detection region 255 of the amplification unit 111 and a sealing sheet 191 to be described later can transmit light. Further, a heating unit 233 configured by a heater or the like is provided on the channel surface side of the amplification unit 111 so as to avoid the detection region 255.

  In FIG. 3B, the A-A ′ cross section of the amplifying unit 111 is a substantially quadrangular shape with rounded corners, and the tip of the narrow channel 113 is open to the tip of the protrusion 115. On the other hand, an exhaust valve 151 is provided on the wall surface 111 b facing the protrusion 115. Each flow path formed on the micro test chip 100 is sealed from the flow path surface side of the micro test chip 100 by a sealing sheet 191.

  As described above with reference to FIG. 3A, the detection region 255 is provided near the center of the amplification unit 111, and both surfaces of the micro inspection chip 100 are obtained by a reaction in the amplification unit 111 across the detection region 255. A detection unit 250 is provided for optically detecting a target substance contained in the produced solution. The detection unit 250 includes, for example, a light source 251 disposed on the back surface side of the micro inspection chip 100 and a light receiving element 253 disposed on the flow path surface side. This is a so-called transmission type configuration. Of course, a so-called reflective configuration in which the light source 251 and the light receiving element 253 are disposed on the same side of the micro inspection chip 100 may be used.

  Further, a heating unit 233 configured by a heater or the like is provided on the channel surface side of the amplification unit 111 so as to avoid the detection region 255. Any transparent heater that does not affect detection by the detection unit 250 may be disposed on the entire flow path surface side of the amplification unit 111. The heating unit 233 is driven and controlled by the drive control unit 270 shown in FIG.

  Next, a state where the reagent 123 and the sample 133 flow into the amplification unit 111 from the narrow channel 113 will be described with reference to FIGS. 4 and 5. FIG. 4 is a schematic diagram showing a state in which the reagent 123 and the sample 133 flow into the amplification unit 111 from the narrow channel 113. FIG. 4A is a diagram seen from the channel surface side of the micro test chip 100. FIG. FIG. 4B is a view showing the AA ′ cross section of FIG.

  4 (a) and 4 (b), the reagent 123 and the sample 133 sent as a laminar flow in the mixed liquid channel 141 and the narrow channel 113 discharge the air in the amplification unit 111 from the exhaust valve 151. While flowing into the amplifying unit 111 from the narrow channel 113 opened at the tip of the projection 115. Since the inner wall surface of the amplification unit 111 is hydrophobic and the tip of the projection 115 is also hydrophobic, the mixture 161 is hemispherical from the tip of the projection 115 due to the surface tension of the mixture 161 of the reagent 123 and the sample 133. It spreads in a shape.

  The amplification unit 111 is configured so that the surface of the mixed solution 161 remains on the amplification unit 111 even when the mixture 161 of the reagent 123 and the sample 133 quantified in the reagent storage unit 121 and the sample storage unit 131 is fed into the amplification unit 111. The inner wall surfaces 111a and 111b and the top surface 111c of the amplifying unit 111 are not touched. As a result, convection is generated in the mixed solution 161 due to the surface tension of the mixed solution 161, and mixing is promoted.

  FIG. 5 is a schematic diagram showing a state in which the entire amount of the liquid mixture 161 has been fed into the amplifying unit 111. FIG. 5A is a view seen from the flow path surface side of the micro test chip 100, and FIG. It is the figure which showed the AA 'cross section of Fig.5 (a) with the flow-path surface down.

  5 (a) and 5 (b), the entire amount of the mixed solution 161 is fed into the amplifying unit 111 and heated by the heating unit 233 while maintaining the hemispherical shape, thereby amplifying the reaction. As a result, the product liquid 161 is obtained. The target substance in the product solution 161 generated by the reaction is optically detected by the detection unit 250.

  As described above, the amplification unit 111 does not touch the inner wall surfaces 111a and 111b of the amplification unit 111 or the top surface 111c of the amplification unit 111 even when the entire amount of the mixture solution 161 is fed. Since it has a volume, the reaction of the liquid mixture 161 is promoted by the surface tension of the liquid mixture 161 even when the reaction in the liquid mixture 161 is amplified by heating by the heating unit 233.

  In the present embodiment, the specimen and the reagent are fed by feeding the driving liquid by the micropump. However, it is not always necessary to use the liquid pump such as the micropump, and the air pump The sample or reagent may be directly fed using

  As described above, according to the embodiment of the present invention, the protruding portion 115 that protrudes the mixed solution 161 of the reagent 123 and the specimen 133 from the inner wall 111 a of the amplification unit 111 to the inside of the amplification unit 111 in a beak shape. The mixed solution 161 can be quickly mixed by flowing into the amplifying unit 111 from the narrow channel 113 opened at the tip of the liquid crystal so that the mixed solution 161 does not touch the wall surface of the amplifying unit.

  In addition, by heating the mixed solution 161 using the heating unit 233 in the amplification unit 111, the mixed solution 161 can be efficiently reacted to obtain the product solution 161. Furthermore, since the target substance in the product solution 161 is detected using the detection unit 250 in the amplification unit 111, the target substance can be efficiently detected from the product solution 161 obtained by the reaction. In addition, since all of the mixing, heating, reaction, and detection described above are performed in the amplifying unit 111, it is excellent in space saving and suitable for downsizing and cost reduction of the micro inspection chip.

  Next, an example of the micropump 211 used in the above-described embodiment will be described with reference to FIG. As the micro pump 211, various types such as a check valve type pump provided with a check valve in an inflow / outflow hole of a valve chamber provided with an actuator can be used, but a piezoelectric pump using a piezoelectric element as a drive source is used. Is preferred. 6 is a schematic diagram showing an example of the configuration of the micropump 211. FIG. 6A is a cross-sectional view showing an example of a piezo pump, FIG. 6B is a top view thereof, and FIG. 6C. FIG. 6 is a cross-sectional view showing another example of a piezo pump.

  6A and 6B, the micropump 211 includes a substrate 402 on which a first liquid chamber 408, a first channel 406, a pressurizing chamber 405, a second channel 407, and a second liquid chamber 409 are formed. The upper substrate 401 stacked on the substrate 402, the vibration plate 403 stacked on the upper substrate 401, the piezoelectric element 404 stacked on the side of the vibration plate 403 facing the pressurizing chamber 405, and the driving of the piezoelectric element 404 A drive unit (not shown) is provided. The drive unit and the two electrodes on both surfaces of the piezoelectric element 404 are connected by wiring using a flexible cable or the like, and a drive voltage is applied to the piezoelectric element 404 by the drive circuit of the drive unit through the wiring. .

  As an example, a photosensitive glass substrate having a thickness of 500 μm is used as the substrate 402, and etching is performed until the depth reaches 100 μm, whereby the first liquid chamber 408, the first flow path 406, the pressurizing chamber 405, the second A flow path 407 and a second liquid chamber 409 are formed. The first channel 406 has a width of 25 μm and a length of 20 μm. The second channel 407 has a width of 25 μm and a length of 150 μm.

  By stacking the upper substrate 401, which is a glass substrate, on the substrate 402, the upper surfaces of the first liquid chamber 408, the first flow path 406, the second liquid chamber 409, and the second flow path 407 are formed. A portion of the upper substrate 401 that corresponds to the upper surface of the pressurizing chamber 405 is processed by etching or the like to penetrate therethrough.

  A vibration plate 403 made of thin glass having a thickness of 50 μm is laminated on the upper surface of the upper substrate 401, and a piezoelectric element 404 made of, for example, lead zirconate titanate (PZT) ceramic having a thickness of 50 μm is laminated thereon. It is affixed. Due to the drive voltage from the drive unit, the piezoelectric element 404 and the vibration plate 403 attached thereto are vibrated, whereby the volume of the pressurizing chamber 405 is increased or decreased.

  The first flow path 406 and the second flow path 407 have the same width and depth, and the length of the second flow path 407 is longer than that of the first flow path 406. Then, when the differential pressure increases, turbulent flow is generated at and around the entrance / exit of the flow path, and the flow path resistance increases. On the other hand, since the length of the flow path in the second flow path 407 is long, it tends to become a laminar flow even if the differential pressure increases, and the rate of change in flow path resistance with respect to the change in differential pressure is smaller than that in the first flow path 406. Become. That is, the relationship of the ease of liquid flow between the first channel 406 and the second channel 407 changes depending on the magnitude of the differential pressure. Utilizing this, the drive voltage waveform for the piezoelectric element 404 is controlled to perform liquid feeding.

  For example, the vibration plate 403 is quickly displaced inward of the pressurizing chamber 405 by the driving voltage for the piezoelectric element 404 to reduce the volume of the pressurizing chamber 405 while applying a large differential pressure, and then is removed from the pressurizing chamber 405. When the volume of the pressurizing chamber 405 is increased while slowly displacing the vibration plate 403 in the direction and applying a small differential pressure, the fluid moves in the direction from the pressurizing chamber 405 to the second liquid chamber 409 (B in FIG. 6A). Direction).

  Conversely, the diaphragm 403 is quickly displaced outward from the pressurizing chamber 405 to increase the volume of the pressurizing chamber 405 while giving a large differential pressure, and then the diaphragm 403 is slowly moved inward from the pressurizing chamber 405. When the volume of the pressurizing chamber 405 is decreased while being displaced to give a small differential pressure, the fluid is fed from the pressurizing chamber 405 toward the first liquid chamber 408 (A direction in FIG. 6A). .

  Note that the difference in the flow rate resistance change ratio with respect to the change in differential pressure in the first flow path 406 and the second flow path 407 is not necessarily due to the difference in the length of the flow path, but is based on other geometric differences. It may be a thing.

  According to the micropump 211 configured as described above, the liquid feeding direction and the liquid feeding speed of a desired fluid can be controlled by changing the driving voltage and frequency of the pump. Although not shown in FIGS. 6A and 6B, the first liquid chamber 408 is provided with a port connected to the driving liquid tank 215, and the first liquid chamber 408 plays the role of a “reservoir”. The driving liquid is supplied from the driving liquid tank 215 at the port. The second liquid chamber 409 forms a flow path of the micro pump unit 210, and there is a chip connection part 213 at the tip, which is connected to the micro test chip.

  In FIG. 6C, the micropump 211 includes a silicon substrate 471, a piezoelectric element 404, a substrate 474, and a flexible wiring (not shown). The silicon substrate 471 is obtained by processing a silicon wafer into a predetermined shape by a photolithography technique, and by etching, a pressurizing chamber 405, a diaphragm 403, a first channel 406, a first liquid chamber 408, a second channel 407, A second liquid chamber 409 is formed.

  The substrate 474 is provided with a port 472 above the first liquid chamber 408 and a port 473 above the second liquid chamber 409. For example, when the micropump 211 is separate from the micro test chip 100 Can communicate with the pump connection of the micro test chip 100 via the port 473. For example, the micro pump 211 can be connected to the micro test chip 100 by superimposing the substrate 474 in which the ports 472 and 473 are perforated and the vicinity of the pump connection part of the micro test chip 100 on each other.

  Further, as described above, since the micropump 211 is obtained by processing a silicon wafer into a predetermined shape by photolithography technology, a plurality of micropumps 211 can be formed on one silicon substrate. . In this case, it is desirable that the driving liquid tank 215 is connected to the port 472 opposite to the port 473 connected to the micro test chip 100. When there are a plurality of micropumps 211, their ports 472 may be connected to a common drive fluid tank 215.

  The above-described micropump 211 is small in size, has a small dead volume due to piping from the micropump 211 to the micro inspection chip 100, etc., has a small pressure fluctuation, and can instantaneously and accurately control discharge pressure. Accurate liquid feed control at 270 is possible.

  In the micro test chip 100 according to the embodiment of the present invention, water repellent valves are provided upstream and downstream of the reagent reservoir 121 and the specimen reservoir 131. The narrow channel 113 has the same structure as the water repellent valve. Here, the structure and operation of the water repellent valve will be described with reference to FIG. FIG. 7 is a schematic diagram for explaining the structure and operation of the water repellent valve. FIG. 7A shows a state in which liquid feeding is blocked by the water repellent valve, and FIG. Indicates that liquid is being pumped over the valve.

  In FIG. 7A, the water repellent valve 501 is configured by a small-diameter liquid feed control passage 511. The liquid feed control passage 511 has a cross sectional area S1 (a cross sectional area of a cross section perpendicular to the liquid feeding direction) smaller than a cross sectional area S2 of the upstream flow path 521 and a cross sectional area S3 of the downstream flow path 523. It is a narrow channel.

  When the flow path wall 531 is formed of a hydrophobic material such as plastic resin, the liquid 541 filled in the upstream flow path 521 flows into the liquid supply control path 511 and the liquid supply control path 511. And passage to the downstream flow path 523 are restricted by the difference in surface tension between the flow path wall 531 at the boundary between the downstream flow path 523 and the downstream flow path 523.

  In FIG. 7B, when the liquid 541 flows out to the downstream channel 523, a liquid feed pressure P equal to or higher than a predetermined pressure is applied by a micropump (not shown), thereby resisting the surface tension. 541 is pushed out from the liquid feeding control passage 511 to the downstream flow passage 523. After the liquid 541 flows out to the downstream channel 523, the liquid 541 moves to the downstream channel 523 without maintaining the liquid feeding pressure P required to push the tip of the liquid 541 to the downstream channel 523. It will flow.

  That is, until the liquid supply pressure in the positive direction from the upstream flow path 521 to the downstream flow path 523 reaches the predetermined pressure P, the passage of the liquid 541 from the liquid supply control path 511 is blocked, and the predetermined pressure The liquid 541 passes through the liquid supply control passage 511 when a liquid supply pressure equal to or higher than P is applied.

  When the flow path wall 531 is formed of a hydrophilic material such as glass, it is necessary to apply a water-repellent coating, for example, a fluorine-based coating, to at least the inner surface of the liquid feeding control passage 511.

  As described above, the sizes of the upstream flow path 521, the downstream flow path 523, and the liquid supply control passage 511 are not particularly limited as long as the passage of the liquid 541 to the upstream flow path 521 and the downstream flow path 523 can be regulated. However, as an example, the liquid supply control passage 511 is formed so that the vertical and horizontal dimensions are about 25 μm × 25 μm with respect to the upstream flow path 521 and the downstream flow path 523 whose vertical and horizontal dimensions are 150 μm × 300 μm.

  As described above, according to the present invention, a mixture of a plurality of types of liquid is efficiently flowed into the amplifying unit from the tip of the protruding portion protruding into the amplifying unit in the form of a beak. Can be mixed. Moreover, a plurality of types of liquids can be mixed efficiently by preventing the surface of the mixed liquid from coming into contact with the wall surface of the amplification unit. Furthermore, the reaction is amplified by heating in the amplification unit to obtain a product solution, and the target substance in the living liquid is detected in the amplification unit, so that multiple types of liquids can be reacted efficiently and the target product can be obtained from the resulting product solution. A substance can be detected, and a micro inspection chip and an inspection apparatus suitable for downsizing and cost reduction can be provided.

  The detailed configuration and detailed operation of each component constituting the micro inspection chip and the inspection apparatus according to the present invention can be changed as appropriate without departing from the spirit of the present invention.

It is a schematic diagram which shows an example of the test | inspection apparatus in this invention. It is a schematic diagram which shows the structure of the principal part of the micro test | inspection chip in this invention. It is a schematic diagram which shows the structure of the main flow paths of embodiment of this invention centering on the amplification part. It is a schematic diagram which shows the state into which the reagent and the sample flowed into the amplification part from the narrow channel. It is a schematic diagram which shows the state by which the liquid mixture was sent in the whole quantity in the amplification part. It is a schematic diagram which shows one example of a structure of a micropump. It is a schematic diagram for demonstrating the structure and operation | movement of a water repellent valve.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Test | inspection apparatus 100 Micro test | inspection chip 111 Amplification part 111a Amplification part wall surface 111b Amplification part wall surface 111c Amplification part top surface 113 Narrow channel 115 Protrusion part 121 Reagent storage part 123 Reagent 125a Water repellent valve 125b Water repellent valve 127 Reagent inlet 129 Sealing Member 131 Specimen storage part 133 Specimen 135a Water repellent valve 135b Water repellent valve 137 Specimen inlet 139 Sealing member 141 Mixed liquid flow path 151 Exhaust valve 161 Mixed liquid or generated liquid 191 Sealing sheet 210 Micropump unit 211 Micropump 213 Chip Connection part 215 Drive liquid tank 216 Drive liquid 217 Drive liquid supply part 230 Heating / cooling unit 231 Cooling part 233 Heating part 250 Detection part 251 Light source 253 Light receiving element 255 Detection area 270 Drive control part 401 On Substrate 402 Substrate 403 Diaphragm 404 Piezoelectric element 405 Pressurization chamber 406 First flow path 407 Second flow path 408 First liquid chamber 409 Second liquid chamber 471 Silicon substrate 472 Port 473 Port 474 Substrate 501 Water repellent valve 511 Liquid feed control Passage 521 Upstream channel 523 Downstream channel 531 Channel wall 541 Liquid

Claims (6)

A liquid mixture flow path for sending a liquid mixture of a plurality of types of liquids downstream;
In a micro test chip including an amplification unit that communicates with the downstream of the mixed liquid channel and amplifies a reaction of the mixed liquid by heating to obtain a product liquid.
The communication part between the mixed liquid channel and the amplification part is a narrow channel whose channel width is narrower than the mixed liquid channel,
The micro-inspection chip, wherein the most downstream portion of the narrow channel opens at a tip portion of a protruding portion protruding in a beak shape from an inner wall of the amplification unit. 2. The micro test chip according to claim 1, wherein the amplification unit has a gap between a side surface and an upper surface of an inner wall of the amplification unit and the mixed solution even when the entire amount of the mixed solution is fed. The micro test chip according to claim 1, wherein an inner wall of the amplification unit is hydrophobic. 4. The micro test chip according to claim 1, wherein the amplifying unit has a detection region for detecting a target substance contained in the product solution. 5. 5. The micro test chip according to claim 1, further comprising a plurality of liquid storage portions that quantitate and store a plurality of the liquids upstream of the mixed liquid channel. The micro inspection chip according to any one of claims 1 to 5,
A micropump for feeding the liquid mixture;
A heating unit for heating the mixed solution;
An inspection apparatus comprising: a detection unit that detects a target substance contained in the product liquid.

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