JP2010025621A - Micro inspection chip, and liquid mixing sending method of micro inspection chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a micro inspection chip and a liquid mixing sending method of the micro inspection chip, stably removing gas between a plurality of liquids, mixing easily the plurality of liquids, and sending the liquids downstream. <P>SOLUTION: This micro inspection chip is equipped with a channel for sending liquid therethrough, and a storage part for storing the liquid sent from the channel. The micro inspection chip capable of stably removing gas among the plurality of liquids, and mixing easily the plurality of liquids can be provided by forming irregular structure on the wall surface of the storage part. Further, the micro inspection chip capable of sending the mixed liquid to the downstream after mixing the plurality of liquids can be provided by reducing the capacity of the storage part furthermore than the total volume of the mixed liquid of the plurality of liquids. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a micro test chip and a liquid mixing and feeding method of the micro test chip, and more particularly, testing and analysis of biological materials by gene amplification reaction, antigen-antibody reaction, etc., testing and analysis of other chemical substances, organic synthesis, etc. The present invention relates to a micro test chip used for chemical synthesis of a target compound and a liquid mixing and feeding method of the micro test chip.

  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 (hereinafter referred to as a micro inspection chip) integrated on a 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 such as those found in genetic testing, skilled techniques, and operation of equipment are required, micro test chips that excel in automation, speed-up, and simplification are cost-effective and require sample volume. Because it enables analysis not only for the required time but also for any time and place, the benefits are great.

  In the micro test chip as described above, it is important to feed and mix a plurality of liquids such as specimens and reagents used for the test accurately as necessary. If a plurality of liquids such as specimens and reagents cannot be accurately fed and mixed, the reaction and the detection result are greatly affected. In order to mix a plurality of liquids such as specimens and reagents, it is necessary to remove gas such as air and inert gas between the plurality of liquids.

  Therefore, as a method often used conventionally, there is a method of removing gas at the timing of merging in a Y-shaped flow path. In this case, it is necessary to arrange a plurality of liquid storage portions in parallel, which is a direction in which the micro inspection chip becomes larger. In addition, a lot of pumps for liquid feeding are required. Furthermore, in the case of mixing in the Y-shaped flow path, since the liquid flow in the flow path after the merge is mainly laminar flow, a long flow path for mixing is necessary. It is a direction to become larger.

  On the other hand, when a plurality of liquid reservoirs are arranged in series, only one pump for liquid feeding is required, but it is difficult to remove the gas between the liquids.

Therefore, in FIG. 4 of Patent Document 2, a plurality of thin tubes are provided between the two conduits, and the liquid is prevented from entering by the flow resistance difference between the thin tubes, so that the gas between the plurality of liquids is removed through the thin tubes. A method of mixing a plurality of liquids is disclosed. According to this method, it is possible to remove and mix the gas between a plurality of liquid masses.
JP 2004-28589 A JP 2000-27813 A

  However, in the method proposed in Patent Document 2, in order to send the mixed liquid further downstream, a valve for switching the liquid feeding direction is essential for the configuration, and the configuration of the micro inspection chip becomes complicated. It will be expensive. In addition, liquid feeding control is complicated, which causes the inspection system itself to become complicated and expensive.

  The present invention has been made in view of the above circumstances, and by simply devising the configuration of the flow path, the gas between the plurality of liquids can be stably removed, the plurality of liquids can be easily mixed, and the liquid can be sent downstream. It is an object of the present invention to provide a micro test chip and a liquid mixing and feeding method for the micro test chip.

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

1. A flow path for feeding liquid;
In a micro inspection chip comprising a reservoir that communicates with the flow path and stores the liquid fed from the flow path.
The micro inspection chip, wherein the storage portion has a concavo-convex structure formed on a wall surface thereof.

  2. 2. The micro inspection chip according to 1 above, wherein the concavo-convex structure has a size and a shape that allows only the gas to enter without allowing the liquid to enter inside due to the action of surface tension.

  3. 3. The micro test chip according to 1 or 2, wherein the uneven structure is a plurality of columnar protrusions arranged on the wall surface.

  4). 4. The micro inspection chip according to 3 above, wherein the columnar protrusion is a columnar protrusion having a polygonal or circular cross section.

5). The storage section has an upstream communication section communicating with the upstream flow path and a downstream communication section communicating with the downstream flow path,
3. The micro inspection chip according to 1 or 2, wherein the concavo-convex structure is one or a plurality of grooves provided on the wall surface connecting the upstream communication portion and the downstream communication portion. .

  6). 6. The micro inspection chip according to any one of 3 to 5, wherein a tip of the concavo-convex structure is a sharp edge.

7). A flow path substrate in which grooves constituting the flow path and the reservoir are formed on the surface;
1 to 6 characterized in that the concave-convex structure is formed on a wall surface of the groove, and is provided with a top plate functioning as a lid for the flow path and the storage section by being bonded to the flow path substrate. The micro inspection chip according to any one of the above.

  8). 8. The micro inspection chip according to any one of 1 to 7, wherein the concavo-convex structure has liquid repellency.

9. From the first liquid that is partitioned by gas to the nth liquid (n is a positive integer) is sequentially sent to the reservoir,
The volume of the reservoir is greater than or equal to the volume of the liquid mixture of the (n-1) th liquid from the first liquid, and smaller than the volume of the liquid mixture of the first liquid to the nth liquid. 9. The micro test chip according to any one of 1 to 8, wherein the micro test chip is characterized in that:

  10. 10. The micro test chip according to any one of 1 to 9, wherein the storage unit is a mixing unit that mixes a plurality of the liquids.

  11. The micro inspection according to any one of 1 to 9, wherein the storage unit is a reaction detection unit that mixes a plurality of the liquids and detects a reaction result of the plurality of mixed liquids. Chip.

12 10. A liquid mixing and feeding method for a micro inspection chip according to 9 above,
A mixing step in which first to nth liquids (n is a positive integer) separated from each other by gas are sequentially sent from the flow path to the storage unit and mixed in the storage unit;
A liquid mixture feeding method for a micro inspection chip, comprising: a downstream liquid feeding step in which the mixed liquid mixed in the mixing step is fed downstream.

  According to the present invention, it is provided with a flow path for feeding liquid and a storage section for storing the liquid sent from the flow path, and by forming an uneven structure on the wall surface of the storage section, It is possible to provide a micro inspection chip capable of stably removing gas and easily mixing a plurality of liquids. Furthermore, the micro test | inspection chip which can send a liquid mixture downstream after mixing a some liquid can be provided by making the volume of a storage part smaller than the total volume of the liquid mixture of a some liquid.

  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 using the micro inspection chip of the present invention will be described with reference to FIG. FIG. 1 is a schematic view showing an example of an inspection apparatus using the micro inspection chip of 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 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.

  Here, the micro test chip 100 has a channel substrate 101 on the surface of which a groove-like channel for feeding or storing a liquid such as a specimen or a reagent is formed, and a channel of the channel substrate 101 is formed. The top plate 103 is bonded to the surface and functions as a groove-shaped channel lid of the channel substrate 101. Further, the top plate 103 is provided with a communication port between the micro pump unit 210 and the micro test chip 100.

  The micro pump unit 210 is a pump unit for performing liquid feeding in the micro test chip 100, and includes a micro pump 211, a chip connection unit 213, a driving liquid tank 215, a driving liquid supply unit 217, and the like. The micropump unit 210 includes one or a plurality of micropumps 211. The micropump 211 feeds the liquid in the micro test chip 100 by injecting or sucking the driving liquid 216 into the micro test chip 100. The chip connection unit 213 connects the micropump 211 and the micro inspection chip 100.

  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 micro test chip 100 and the micropump 211 are connected by a chip connection part 213 and communicated with each other. Samples stored in a plurality of storage units in the micro test chip 100 are driven by the driving liquid 216 that is driven into the micro test chip 100 from the micro pump 211 via the chip connection unit 213 by the micro pump 211 being driven. A liquid such as a reagent is fed in the micro test chip 100. Alternatively, liquids such as specimens and reagents stored in a plurality of storage units in the micro test chip 100 are sent in the micro test chip 100 by a gas such as air pushed by the driving liquid 216.

  The heating / cooling unit 230 includes a cooling unit 231, a heating unit 233, and the like, and 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 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 composed of Peltier elements.

  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. Here, a transmitted light type detection unit in which the light source 251 and the light receiving element 253 face each other with the micro inspection chip 100 interposed therebetween is illustrated, but the present invention is not limited to this, and the light source 251 and the light receiving element 253 are juxtaposed. It may be a reflected light type.

  The drive control unit 270 includes a microcomputer, a memory, and the like (not shown), and drives, controls, and detects each unit in the inspection apparatus 1.

  Here, an example in which the micropump 211 that injects or sucks the driving liquid 216 is used as a liquid-feeding pump in the micro test chip 100. However, air that injects or sucks a gas such as air as necessary is shown. It may be replaced with another type of pump such as a pump.

  Next, an example of the entire configuration of the micro inspection chip according to the present invention will be described with reference to FIG. FIG. 2 is a schematic diagram showing an example of the overall configuration of the micro test chip according to the present invention. As described above, the micro test chip 100 includes the flow path substrate 101 having a groove-shaped flow path formed on the surface thereof for feeding or storing a liquid such as a specimen or a reagent, and the flow path of the flow path substrate 101. It is assumed that it is composed of a top plate 103 that is bonded to the formed surface and functions as a groove-shaped channel lid of the channel substrate 101.

  FIG. 2A is a schematic diagram showing an example of the configuration of the flow channel 900 of the micro test chip 100, and is a plan view of the flow channel 900 viewed from the top plate 103 side, that is, from the direction of arrow B in FIG. FIG. The channel 900 includes a reagent storage unit 901, a sample storage unit 903, a mixing reaction unit 905, a pump communication port 907, an exhaust port 909, and a fine channel that connects the above-described units.

  The reagent container 901 is provided with a reagent injection port 901a. After the reagent is injected, the reagent injection port 901a is sealed with a sealing member 901b. Similarly, the sample storage portion 903 is provided with a sample injection port 903a. After sample injection, the sample injection port 903a is sealed with a sealing member 903b.

  The reagent stored in the reagent storage unit 901 and the sample stored in the sample storage unit 903 are pushed by the driving liquid injected from the pump communication port 907 by a micropump (not shown) and sequentially sent to the mixing reaction unit 905. To be mixed. The mixed solution in which the reagent and the sample are mixed reacts, and the target substance obtained by the reaction is detected by the mixing reaction unit 905. Here, the mixing reaction unit 905 functions as a storage unit, a mixing unit, and a reaction detection unit in the present invention.

  FIG. 2B is a cross-sectional view taken along the line A-A ′ of FIG. The channel substrate 101 is formed with grooves that form narrow and shallow fine channels and channels such as a reagent container 901, a sample container 903, and a mixture reaction unit 905 that are wide and deep. Each of the flow paths is formed by being covered with a top plate 103. The top plate 103 is provided with a pump communication port 907 and is connected to a micro pump (not shown) via a chip connection portion 213.

  Similarly, the top plate 103 is provided with an exhaust port 909, and air in the flow path is exhausted from the exhaust port 909 to the outside when the reagent and the specimen are sent. Further, a detection unit 250 is provided at a position facing the mixing reaction unit 905 with the top plate 103 interposed therebetween. In FIG. 1, the detection unit 250 is an example of a transmitted light type, but here, a reflected light type in which a light source 251 and a light receiving element 253 are juxtaposed on the top plate 103 side is illustrated.

  The top plate 103 is provided with a reagent inlet 901a and a specimen inlet 903a. After the reagent and specimen are injected, the reagent inlet 901a and the specimen inlet 903a are sealed with a sealing member 901b and a sealing member 903b. Stopped.

  The present invention is mainly used in a storage section that is a flow path for mixing and reacting a plurality of liquids such as the specimen and reagents such as the above-described mixing reaction section 905 or detecting a reaction result.

(First embodiment)
Next, a first embodiment of the micro test chip according to the present invention will be described with reference to FIG. FIG. 3 is a schematic diagram showing the configuration of the first embodiment of the micro test chip 100, and FIG. 3A shows the configuration of the storage portion 111 formed on the surface of the flow path substrate 101. 3) is a plan view seen from the direction of arrow B, and FIG. 3B is a cross-sectional view taken along the line CC ′ of FIG. Moreover, FIG.3 (c) is the top view seen from the arrow B direction of FIG.3 (b) which shows the other structure of the storage part 111. FIG. Here, the arrow B direction is the same as the arrow B direction of FIG.

  In FIGS. 3A and 3B, the reservoir 111 communicates with the upstream channel 113 and the downstream channel 115. Then, quadrangular columnar protrusions 112r are arranged on the entire inner wall surface of the reservoir 111 on the flow path substrate 101 side. Here, the quadrangular columnar projection 112r functions as a concavo-convex structure in the present invention.

  In FIG. 3C, cylindrical projections 112c are arranged on the entire inner wall surface of the reservoir 111 on the flow path substrate 101 side, instead of the above-described square columnar projections 112r. Here, the columnar projection 112c also functions as the concavo-convex structure in the present invention. In addition, the C-C 'cross section of FIG.3 (c) is the same as FIG.3 (b).

  The cross-sectional area, length, spacing between the protrusions, etc. of the above-described quadrangular columnar protrusion 112r or cylindrical protrusion 112c (hereinafter referred to as protrusion 112 without distinction) Due to the surface tension, it is set to such a fine dimension that it cannot enter between the projections 112 and only gas can enter between the projections 112.

  In order to further increase the effect of the surface tension, it is desirable that the tip of the projection 112 has a rounded corner and is a so-called sharp edge. Moreover, it is desirable that the inner wall surface of the projection 112 itself and the storage portion 111 at the base of the projection 112 on the side of the flow path substrate 101 have water repellency.

  In order to provide water repellency, for example, the flow path substrate 101 may be formed of a water repellent resin material such as polypropylene, and when it is necessary to use a hydrophilic material for the flow path substrate 101, Water repellent treatment such as coating the whole or the above-described portion requiring water repellency with a fluorine-based material may be performed.

  It is conceivable to arrange the protrusions 112 on the inner wall surface of the storage unit 111 on the top plate 103 side. However, if the protrusions 112 are provided on the top plate 103 side, the protrusions 112 are formed due to variations in the bonding state between the flow path substrate 101 and the top plate 103. There is a possibility that the water repellency of the 112 may vary, and in the worst case, the liquid may enter between the arrangement of the protrusions 112. If arranged on the flow path substrate 101 side, the arrangement of the protrusions 112 can be formed by molding, so that stable water repellency can be obtained.

  Next, a method for mixing and feeding a plurality of liquids in the first embodiment will be described with reference to FIG. FIG. 4 is a schematic diagram for explaining a method of mixing and feeding a plurality of liquids in the first embodiment. Here, an example in which three liquids including another reagent (referred to as reagent B) in addition to the specimen and reagent (referred to as reagent A) in FIG. 2 are mixed and sent downstream will be described.

  In FIG. 4A, the reservoir 111 communicates with the upstream flow path 113 and the downstream flow path 115, and protrusions 112 are arranged on the entire inner wall surface of the reservoir 111 on the flow path substrate 101 side. Yes. Here, the first liquid 151 (for example, the specimen) is sent from the upstream flow path 113 to the storage unit 111 by being pushed by the driving liquid 216 injected from a micro pump (not shown). Here, the volume of the reservoir 111 is set to be sufficiently larger than the volume of the first liquid 151 that is fed.

  In FIG. 4B, when the entire amount of the first liquid 151 flows into the storage unit 111, the first liquid 151 stops and stays in the storage unit 111. However, the first liquid 151 cannot penetrate between the arrangements of the protrusions 112 due to surface tension. Subsequently, the second liquid 155 (for example, reagent A) is pushed from the upstream flow path 113 to the reservoir 111 by being pushed by the driving liquid 216 injected from a micro pump (not shown). Between the first liquid 151 and the second liquid 155, there is a gas 153 such as air or an inert gas that exists in the flow path, but the gas 153 can enter between the arrangement of the protrusions 112. By feeding the second liquid 155, the gas 153 passes between the arrangement of the protrusions 112 as shown by the arrows, passes the first liquid 151, and flows out to the downstream flow path 115.

  In FIG. 4C, when all of the gas 153 between the first liquid 151 and the second liquid 155 flows out to the downstream flow path 115 by the feeding of the second liquid 155, the first liquid 151 and The second liquid 155 merges and is mixed to become the first mixed liquid 156. Here, the volume of the reservoir 111 is set to be sufficiently larger than the volume of the first mixed liquid 156. Therefore, the first mixed liquid 156 stops and stays in the storage unit 111. However, the first mixed liquid 156 cannot enter between the arrangement of the protrusions 112 due to surface tension.

  Subsequently, the third liquid 157 (for example, reagent B) is pushed from the upstream flow path 113 to the storage unit 111 by being pushed by the driving liquid 216 injected from a micro pump (not shown). By sending the third liquid 157, the gas 153 between the first liquid mixture 156 and the third liquid 157 also passes between the arrangements of the protrusions 112, overtakes the first liquid mixture 156, and flows downstream. It flows out to the road 115.

  In FIG. 4D, when all the gas 153 between the first mixed liquid 156 and the third liquid 157 flows out to the downstream flow path 115, the first mixed liquid 156 and the third liquid 157 The two are mixed and mixed to become the second mixed liquid 158. This is the mixing step in the present invention.

  In FIG. 4 (e), the volume of the storage unit 111 is set slightly smaller than the volume of the second mixed liquid 158. When the volume of the second liquid mixture 158 in which the first liquid mixture 156 and the third liquid 157 are mixed exceeds the volume of the reservoir 111, the gas between the second liquid mixture 158 and the driving liquid 216 153 cannot pass through the array of protrusions 112. Therefore, the second mixed liquid 158 is pushed by the driving liquid 216 injected from a micro pump (not shown) via the gas 153 in the upstream flow path 113 and starts to flow out to the downstream flow path 115, The liquid is sent to. This is the downstream liquid feeding step in the present invention.

  In the first embodiment, the projection 112 is a quadrangular columnar projection 112r or a columnar projection 112c. However, the present invention is not limited to this, and for example, a columnar projection having a polygonal cross section such as a triangular column or a hexagonal column is used. It may be a protrusion.

  As described above, according to the first embodiment, only gas passes by arranging water-repellent rectangular columnar or columnar protrusions on the entire inner wall surface of the reservoir on the flow path substrate side. Since a possible passage can be secured, it is possible to provide a micro test chip capable of stably removing gases between a plurality of liquids and easily mixing the plurality of liquids. Furthermore, the micro test | inspection chip which can send a liquid mixture downstream after mixing a some liquid can be provided by making the volume of a storage part smaller than the total volume of the liquid mixture of a some liquid.

(Second Embodiment)
Next, a second embodiment of the micro test chip according to the present invention will be described with reference to FIG. FIG. 5 is a schematic diagram showing the configuration of the second embodiment of the micro test chip 100, and FIG. 5A shows the configuration of the reservoir 111 formed on the surface of the flow path substrate 101. ) Is a plan view seen from the direction of arrow B, FIG. 5B is a sectional view taken along the line DD ′ of FIG. 5A, and FIG. 5C is a sectional view taken along the line EE ′ of FIG. . Here, the arrow B direction is the same as the arrow B direction of FIG.

  5A, 5B, and 5C, the reservoir 111 communicates with the upstream flow path 113 and the upstream communication part 111a, and communicates with the downstream flow path 115 and the downstream communication part 111b. A single groove 112s is provided on the inner wall surface of the reservoir 111 on the flow path substrate 101 side so as to connect the upstream communication portion 111a and the downstream communication portion 111b. Here, the groove 112s functions as a concavo-convex structure in the present invention.

  The width, depth, and the like of the groove 112s described above are such that the liquid flowing into the storage part 111 cannot enter the groove 112s due to the surface tension, and only gas enters the groove 112s. Is set to such a fine dimension that can be

  In order to increase the effect of the surface tension, it is desirable that the opening portion of the groove 112s to the storage portion 111 is not rounded but has a so-called sharp edge. Further, it is desirable that the inside of the groove 112s has water repellency.

  In order to provide water repellency, for example, the flow path substrate 101 may be formed of a water repellent resin material such as polypropylene, and when it is necessary to use a hydrophilic material for the flow path substrate 101, Water repellent treatment such as coating the whole or the inside of the groove 112s with a fluorine-based material may be performed.

  It is conceivable to form the groove 112 s on the inner wall surface of the storage unit 111 on the top plate 103 side. However, if the groove 112 s is provided on the top plate 103 side, the groove 112 s There is a possibility that the water repellency of 112s may vary, and in the worst case, the liquid may enter the groove 112s. If formed on the flow path substrate 101 side, the groove 112s can be formed by molding, so that stable water repellency can be obtained.

  Next, a method for mixing and feeding a plurality of liquids in the second embodiment will be described with reference to FIG. FIG. 6 is a schematic diagram for explaining a method of mixing and feeding a plurality of liquids in the second embodiment. Here, an example in which the specimen and the reagent in FIG. 2 are mixed and sent downstream is described.

  In FIG. 6A, the reservoir 111 communicates with the upstream flow path 113 and the upstream communication section 111a, and communicates with the downstream flow path 115 and the downstream communication section 111b. A single groove 112s is provided on the inner wall surface of the reservoir 111 on the flow path substrate 101 side so as to connect the upstream communication portion 111a and the downstream communication portion 111b. Here, the first liquid 151 (for example, the specimen) is sent from the upstream flow path 113 to the storage unit 111 by being pushed by the driving liquid 216 injected from a micro pump (not shown).

  Here, the volume of the reservoir 111 is set to be sufficiently larger than the volume of the first liquid 151 that is fed. Therefore, when the entire amount of the first liquid 151 flows into the storage unit 111, the first liquid 151 stops in the storage unit 111 and stays there. However, the first liquid 151 cannot enter the groove 112s due to surface tension. Subsequently, the second liquid 155 (for example, a reagent) is pushed from the upstream flow channel 113 to the storage unit 111 by being pushed by the driving liquid 216 injected from a micro pump (not shown).

  Between the first liquid 151 and the second liquid 155, there is a gas 153 such as air or an inert gas existing in the flow path. However, since the gas 153 can enter the groove 112s, the second liquid As a result of the feeding of 155, the gas 153 passes through the groove 112s as shown by the arrow in the figure, passes the first liquid 151, and flows out to the downstream flow path 115.

  In FIG. 6B, when all of the gas 153 between the first liquid 151 and the second liquid 155 flows out to the downstream flow path 115 by sending the second liquid 155, the first liquid 151 and The second liquid 155 merges and is mixed to become a mixed liquid 156. This is the mixing step in the present invention.

  In FIG. 6C, the volume of the storage unit 111 is set slightly smaller than the volume of the mixed solution 156. When the volume of the liquid mixture 156 in which the first liquid 151 and the second liquid 155 are mixed exceeds the volume of the reservoir 111, the gas 153 between the liquid mixture 156 and the driving liquid 216 passes through the groove 112s. Can not be. Therefore, the liquid mixture 156 is pushed by the driving liquid 216 injected from a micro pump (not shown) via the gas 153 in the upstream flow path 113, starts to flow out to the downstream flow path 115, and is sent downstream. To be liquidated. This is the downstream liquid feeding step in the present invention.

  In the second embodiment, the number of grooves 112s is one. However, the number of grooves is not limited to this, and two or more grooves may be used.

  As described above, according to the second embodiment, the inner wall surface on the flow path substrate side of the reservoir has water repellency, and the groove is formed so as to connect the upstream flow path and the downstream flow path. By providing, a passage through which only gas can pass can be secured, so that it is possible to provide a micro test chip capable of stably removing gas between a plurality of liquids and easily mixing the plurality of liquids. Furthermore, the micro test | inspection chip which can send a liquid mixture downstream after mixing a some liquid can be provided by making the volume of a storage part smaller than the total volume of the liquid mixture of a some liquid.

Here, the arrangement of the projections 112 or the size of the grooves 112s into which only the gas cannot enter and the liquid cannot enter will be described. As an example, considering the groove 112s, for example, when the liquid 151 is sent to the storage unit 111 as shown in FIG. 6A, the width of the groove 112s is d, the pressure of the liquid 151 is P, and the surface tension of the liquid 151 Where γ is
P = 2 × γ / d
Given in.

As an example, assuming that a pressure of 1 kPa is applied to the wall surface of the storage unit 111 by feeding the liquid 151, when the liquid 151 is water, the surface tension of water at room temperature is 73 × 10 ⁻³ N / m. Therefore, from the above equation, d = 146 μm. That is, if the width of the groove 112s is 146 μm or less, the liquid 151 (water in this case) cannot enter the groove 112s at room temperature. Since the surface tension generally decreases as the temperature rises, it is actually necessary to determine the width of the groove 112s in consideration of the actual operating temperature range. Furthermore, it is necessary to consider the type of liquid, the water repellent condition of the groove 112s, and the like.

  The depth of the groove is not particularly limited in relation to the surface tension, but when the micro inspection chip is formed by molding, it is preferably several times the width d or less from the viewpoint of moldability.

  From the above, the width d of the groove 112s is preferably 10 μm to 200 μm, and the depth is preferably about 2 to 3 times the width d. For example, the width d = 50 μm and the depth = 100 μm.

  It is considered that almost the same concept can be applied to the arrangement of the protrusions 112, and the interval between the protrusions 112 is preferably 10 μm to 200 μm, and more preferably 10 μm to 50 μm. The thickness and height of the protrusion 112 are not particularly limited, but the thickness (the length of one side in the case of a quadrangular column, the diameter in the case of a cylinder) is 10 μm to 1 mm from the viewpoint of formability as with the groove 112s. The height is preferably about 2 to 3 times the thickness. For example, thickness = 100 μm, height = 200 μm, and spacing = 50 μm.

  As described above, according to the present invention, a flow path for feeding a liquid and a storage section for storing the liquid sent from the flow path are provided, and an uneven structure is formed on the wall surface of the storage section. Thus, it is possible to provide a micro test chip capable of stably removing gases between a plurality of liquids and easily mixing the plurality of liquids. Furthermore, the micro test | inspection chip which can send a liquid mixture downstream after mixing a some liquid can be provided by making the volume of a storage part smaller than the total volume of the liquid mixture of a some liquid.

  It should be noted that the detailed configuration and detailed operation of each component constituting the micro test chip and the liquid mixing and feeding method of the micro test chip 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 using the micro test | inspection chip of this invention. It is a schematic diagram which shows one example of the whole structure of the micro test | inspection chip in this invention. It is a schematic diagram which shows the structure of 1st Embodiment of a micro test | inspection chip. It is a schematic diagram explaining the mixing and liquid feeding method of the some liquid in 1st Embodiment. It is a schematic diagram which shows the structure of 2nd Embodiment of a micro test | inspection chip. It is a schematic diagram explaining the mixing and liquid feeding method of the some liquid in 2nd Embodiment.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Inspection apparatus 100 Micro test | inspection chip 101 Flow path board | substrate 103 Top plate 111 Storage part 111a Upstream side communication part 111b Downstream side communication part 112 Protrusion 112c Cylindrical protrusion 112r Square columnar protrusion 112s Groove 113 Upstream flow path 115 Downstream flow path 151 1st liquid 153 Gas 155 2nd liquid 156 1st liquid mixture 157 3rd liquid 158 2nd liquid mixture 210 Micro pump unit 211 Micro pump 213 Chip connection part 215 Drive liquid tank 216 Drive liquid 217 Drive liquid supply Unit 230 heating / cooling unit 231 cooling unit 233 heating unit 250 detection unit 251 light source 253 light receiving element 255 detection region 270 drive control unit 900 channel 901 reagent storage unit 901a reagent injection port 901b sealing member 903 sample storage unit 903a sample injection port 03b sealing member 905 mixed reaction unit 907 pump communication port 909 outlet

Claims (12)

A flow path for feeding liquid;
In a micro inspection chip comprising a reservoir that communicates with the flow path and stores the liquid fed from the flow path.
The micro inspection chip, wherein the storage portion has a concavo-convex structure formed on a wall surface thereof. 2. The micro test chip according to claim 1, wherein the concavo-convex structure has a size and a shape in which only the gas cannot enter the liquid due to the action of surface tension, and only the gas can enter. 3. The micro inspection chip according to claim 1, wherein the uneven structure is a plurality of columnar protrusions arranged on the wall surface. 4. The micro inspection chip according to claim 3, wherein the columnar protrusion is a columnar protrusion having a polygonal or circular cross section. The storage section has an upstream communication section communicating with the upstream flow path and a downstream communication section communicating with the downstream flow path,
The micro-inspection according to claim 1 or 2, wherein the concavo-convex structure is one or a plurality of grooves provided in the wall surface that connects the upstream communication portion and the downstream communication portion. Chip. The micro inspection chip according to claim 3, wherein a tip of the concavo-convex structure is a sharp edge. A flow path substrate in which grooves constituting the flow path and the reservoir are formed on the surface;
The concavo-convex structure is formed on a wall surface of the groove, and includes the top plate functioning as a lid of the channel and the storage unit by being bonded to the channel substrate. 7. The micro inspection chip according to any one of 6 above. The micro inspection chip according to claim 1, wherein the concavo-convex structure has liquid repellency. From the first liquid that is partitioned by gas to the nth liquid (n is a positive integer) is sequentially sent to the reservoir,
The volume of the reservoir is greater than or equal to the volume of the liquid mixture of the (n-1) th liquid from the first liquid, and smaller than the volume of the liquid mixture of the first liquid to the nth liquid. The micro test chip according to claim 1, wherein the micro test chip is a micro test chip. The micro test chip according to claim 1, wherein the storage unit is a mixing unit that mixes a plurality of the liquids. The micro reservoir according to claim 1, wherein the storage unit is a reaction detection unit that mixes a plurality of the liquids and detects a reaction result of the plurality of mixed liquids. Inspection chip. It is a liquid mixing liquid feeding method of the micro inspection chip according to claim 9,
A mixing step in which first to nth liquids (n is a positive integer) separated from each other by gas are sequentially sent from the flow path to the storage unit and mixed in the storage unit;
A liquid mixture feeding method for a micro inspection chip, comprising: a downstream liquid feeding step in which the mixed liquid mixed in the mixing step is fed downstream.

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