JP2017151035A - Microchip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a microchip that can be adapted for even a sample having a risk of secondary contamination or secondary infection.SOLUTION: The microchip comprises a flow channel in which a liquid in contact with a sample flows, and a closed-system waste liquid tank that expands upon inflow of a liquid from the flow channel. It is preferable that the closed-system waste liquid tank in the microchip to be formed with a stretchable elastic sheet. It is also preferable that the flow channel and the closed-system waste liquid tank in the microchip to be formed by providing a non-bonded portion in a plurality of elastic sheets that are laminated by bonding.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a microchip. In particular, the present invention relates to an inspection microchip.

  In recent years, a technique for automatically performing analysis on a microchip by a chemical / biochemical approach such as DNA (deoxyribonucleic acid) inspection has been developed. For example, Patent Document 1 discloses a microchip for performing sample reaction and analysis and a flow path control mechanism on the microchip.

International Publication No. 2009/119698

  The following analysis has been made from the viewpoint of the present invention. The disclosure of the above prior art document is incorporated herein by reference.

  In the microchip disclosed in Patent Document 1, waste liquid generated during sample extraction, purification, and reaction is discharged to the outside from a disposal hole provided on the microchip. In such a configuration, there is a problem that the user may come into contact with the waste liquid discharged to the outside, which is not suitable for analysis using a sample having a risk of secondary contamination or secondary infection. .

  Therefore, an object of the present invention is to provide a microchip that can be applied to a sample having a risk of secondary contamination or secondary infection.

  According to a first aspect of the present invention, there is provided a microchip including a flow path through which a liquid in contact with a sample flows and a closed waste liquid tank that expands when the liquid flows in from the flow path.

  ADVANTAGE OF THE INVENTION According to this invention, the microchip which can be applied also to the sample with the risk of a secondary contamination or a secondary infection is provided.

It is a figure for demonstrating the outline | summary of the microchip which concerns on one Embodiment. 2 is a diagram illustrating a specific example of a microchip control device 10. FIG. 4 is a diagram for explaining an example of a flow path control mechanism on the microchip 100. FIG. 1 is a perspective view showing an example of the overall configuration of a microchip 100. FIG. FIG. 3 is a diagram illustrating an example of a cross-sectional view of a microchip 100 including a swab receiving unit 112. 2 is a view showing the arrangement of solution tanks and the like in the chip body 111 of the microchip 100. FIG. It is a figure which shows a specific example of the waste liquid tank 122 and the non-return valve structure 123. FIG. It is a figure which shows a specific example of the waste liquid tank 122 and the non-return valve structure 123. FIG. It is a figure which shows a specific example of the waste liquid tank 122 and the non-return valve structure 123. FIG. 6 is a diagram illustrating a specific example of an electrophoresis unit 126. FIG. 4 is a flowchart of processing by the microchip control device 10. It is a figure which shows another example of the waste liquid tank 122 and the non-return valve structure 123. FIG. It is a figure which shows another example of the waste liquid tank 122 and the non-return valve structure 123. FIG.

  DESCRIPTION OF EXEMPLARY EMBODIMENTS Preferred embodiments of the invention will be described in detail with reference to the drawings. Note that the reference numerals of the drawings attached to the following description are added for convenience to each element as an example for facilitating understanding, and are not intended to limit the present invention to the illustrated embodiment.

  FIG. 1 is a diagram for explaining an outline of a microchip according to an embodiment. As shown in FIG. 1, the microchip 100 includes a flow path 113 through which a liquid in contact with a sample flows, and a waste liquid tank 122 that expands when the liquid flows in from the flow path 113. The sample is, for example, biological tissue / cell, body fluid, soil, river water, manure, mixed substance / mixed solution with unknown chemical components, and the like. The liquid in contact with the sample is, for example, a cell lysate or a DNA extract.

  The waste liquid tank 122 is enclosed in the microchip 100, is in a closed system (so-called watertight or closed) in which the liquid in the waste liquid tank 122 is isolated from the outside, and is connected only to the flow path 113. In the waste liquid tank 122, sample residue and liquid in contact with the sample are stored. In this way, after the sample is sealed in the microchip 100, the residue of the sample and the liquid / gas in contact with the sample are not discharged to the outside of the microchip 100 but can be retained inside the microchip 100. . Therefore, it is possible to safely perform analysis of a sample having a risk of secondary contamination or secondary infection using the microchip 100.

[First Embodiment]
In the following embodiments, an example of a microchip 100 for DNA testing and a microchip control device 10 that performs flow path control on the microchip for DNA testing will be described. As shown in FIG. 2, in the microchip control apparatus 10, a table 12 is disposed on a pedestal 11, and a cell lysis unit 13, a PCR (polymerase chain reaction) unit 14, and an electrophoresis unit 15 are disposed on the table 12. . Further, the base 11 and the lid 16 are connected via a hinge, and the lid 16 can be opened and closed.

  The microchip 100 is placed at a predetermined position on the table 12 by fitting the pins provided on the table 12 into the pin holes provided on the microchip 100. The lid 16 is provided with a plurality of pressure holes 17. The region of the lid 16 corresponding to these pressurizing holes 17 penetrates, and the pressurizing hole 17 is connected to the electromagnetic valve 19 via a tube 18. Further, the pressure hole 17 and various control holes on the microchip 100 are connected by closing the lid 16. The pressure hole 17 and the control hole are preferably in close contact with each other through a sealing mechanism such as an O-ring 20.

  The pressure accumulator 21 is filled with a pressurized medium such as compressed air, and the controller 22 controls the electromagnetic valve 19 so that the pressurized medium is taken into and out of the control hole on the microchip 100 through the pressurized hole 17. . The internal pressure of the pressure accumulator 21 is controlled to maintain a predetermined pressure by a pressure sensor and a pump (not shown).

  The lid 16 is provided with a DNA extraction unit 23 for extracting DNA from the lysed cells. The DNA extraction unit 23 is, for example, an electromagnet or a neodymium magnet. The DNA extraction unit 23 moves the magnet closer to the DNA extraction tank 121 or moves the magnet away from the DNA extraction tank 121 under the control of the controller 22.

  The cell lysis unit 13 and the PCR unit 14 include a temperature sensor, a heat transfer material, a Peltier element (thermoelectric element), a heat sink, and the like. The cell lysis unit 13 performs a lysis reaction by heating a solution containing cells, and the PCR unit 14 executes PCR.

  The electrophoresis unit 15 is a mechanism for executing capillary electrophoresis and detection of a fluorescent label. The fluorescent label detection mechanism includes an excitation device such as a halogen lamp, a mercury lamp, and laser light, a filter, a camera, and the like. When a DC voltage is applied to the electrode via the power supply unit 24 and capillary electrophoresis starts, the electrophoresis unit 15 monitors the fluorescent label flowing through the capillary and detects the change in fluorescence luminance over time in a graph. The result is output via the display unit 25.

  The controller 22 can also be realized by a computer program that causes a computer mounted on the microchip control apparatus 10 to execute processing of the microchip control apparatus 10 described in detail later using its hardware.

  As shown in FIG. 3, the microchip 100 is formed by laminating elastic sheets 211 to 214 and a resin plate 215. Desirably, the elastic sheets 211 to 214 are mainly made of silicon rubber or the like having heat resistance, acid resistance and alkali resistance, and stretchability, and the resin plate 215 can control expansion of the elastic sheets 211 to 214. It is desirable to be as hard as possible. A part of the elastic sheets 211 to 214 is non-adhered, and a liquid tank, a flow path, a valve mechanism, and the like are formed by the non-adhered portions. In addition, the broken line in drawing after FIG. 3 shows a non-adhesion location.

  Here, an example of the flow path control mechanism on the microchip 100 will be described with reference to FIGS. As shown in FIGS. 3A to 3C, in the microchip 100, a liquid tank 240A is formed between the elastic sheet 211 and the elastic sheet 212 and connected to the flow paths 250X and 250Y. A portion of the resin plate 215 corresponding to the liquid tank 240A penetrates to form a control hole, and a pressurized medium can be taken in and out of the upper part of the liquid tank 240A through a pressure hole 17A provided in the lid 16. Similarly, the liquid tank 240B is connected to the flow paths 250Y and 250Z, and a pressurized medium can be taken in and out of the upper part of the liquid tank 240B through the pressure hole 17B. The flow paths 250X and Y are closed.

  Under such a premise, as shown in FIG. 3A, the microchip control device 10 first injects a pressurized medium into the valve mechanism 270Z to close the flow path 250Z, and then from the valve mechanism 260Y. The flow path 250Y is opened by releasing the pressurized medium. Then, the microchip control device 10 applies a pressurized medium to the liquid tank 240A through the pressurized hole 17A. As a result, as shown in FIG. 3B, the liquid pushed out from the liquid tank 240A reaches the liquid tank 240B through the flow path 250Y, pushes up the elastic sheet 211, and accumulates in the liquid tank 240B. When the microchip control device 10 determines that the pressure applied to the liquid tank 240A exceeds the predetermined value and has discharged the liquid from the liquid tank 240A, as shown in FIG. A pressurized medium is injected into the valve mechanism 260Y from the upstream side of the path 250Y (that is, the liquid tank 240A side). As a result, the liquid in the flow path 250Y is pushed out to the liquid tank 240B, and the liquid transport is completed. Thereafter, since it is no longer necessary to close the flow path 250X, the microchip control device 10 releases the pressurized medium from the valve mechanism 270X.

  FIG. 4 is a diagram showing a specific example of the microchip 100. As shown in FIG. 4, the microchip 100 includes a chip body 111 and a swab receiving part 112. The chip body 111 and the swab receiving part 112 are connected via an opening 117 and a flow path 113, and the flow path 113 is opened and closed by a valve mechanism 114. The flow path 113 and the valve mechanism 114 will be described later.

  As shown in FIG. 5, the swab receiving portion 112 has a cylindrical shape, and a swab (cotton swab) 115 to which cells are attached is inserted from the upper opening. The inner space of the swab receiving part 112 corresponds to the cell lysis tank 116, and the cell lysis buffer flows into the cell lysis tank 116 from the chip body 111 side through the lower opening. The flow path 113 is formed by a non-adhered portion between the elastic sheets. In the cell lysis tank 116 of FIG. 5, the same flow path control as the flow path control described with reference to FIG. 3 is performed. That is, when the cell lysate is moved to the DNA extraction tank 121 described later, the pressurized medium flows into the cell lysis tank 116 with the valve mechanism 114 opened, and the cell lysis in the cell lysis tank 116 is performed. The liquid is pushed out into the flow path 113. It should be noted that it is desirable to attach a lid, a seal, or the like that prevents the swab 115 from jumping out of the cell lysis tank 116 or scattering of the sample immediately after use of the microchip 100.

  FIG. 6 is a diagram showing the arrangement of solution tanks and the like in the chip body 111 of FIG. In FIG. 6, the flow path 113 and the like are omitted except for a part. As shown in FIG. 6, the chip body 111 has an opening 117 connected to the cell lysis tank 116 (swab receiving portion 112) shown in FIG. The chip body 111 is provided with a buffer / reagent tank 120, a DNA extraction tank 121, a waste liquid tank 122, a check valve structure 123, a PCR tank 124, a weighing tank 125, and an electrophoresis unit 126.

  A cell lysis buffer, a washing buffer, a DNA elution buffer, and the like are injected into the buffer / reagent tank 120. The cell lysis buffer is, for example, an alkaline lysis buffer, and is moved to the cell lysis tank 116 via the opening 117. When a heat treatment or the like is required when lysing cells, the microchip control device 10 or the swab receiving unit 112 is provided with a mechanism necessary for the treatment, such as a heater or a heat transfer plate.

  The cell lysate in the cell lysis tank 116 is moved to the DNA extraction tank 121. In the DNA extraction tank 121, a DNA extraction process is executed. The DNA extraction process will be specifically described. In the DNA extraction tank 121, magnetic beads (silica) are encapsulated in advance. When the DNA in the cell lysate is adsorbed on the magnetic beads, the microchip control device 10 discharges the remaining sample residue in the cell lysate to the waste liquid tank 122. Then, the microchip control apparatus 10 moves the washing buffer from the buffer / reagent tank 120 to the DNA extraction tank 121 and then discharges it to the waste liquid tank 122. Subsequently, the microchip control apparatus 10 moves the DNA elution buffer from the buffer / reagent tank 120 to the DNA extraction tank 121 to elute DNA from the magnetic beads, and further moves the DNA elution buffer to the PCR tank 124. The microchip control device 10 causes the magnetic beads to be discharged together with the cell lysate and the washing buffer by adsorbing the magnetic beads to the neodymium magnet when the cell lysate or the like is discharged from the DNA extraction tank 121. To prevent.

  The DNA extraction method can be modified, for example, by increasing the number of washings with reference to various protocols. Further, the DNA extraction method is not limited to the method using magnetic beads, and for example, a method using a column may be adopted.

  As shown in FIG. 6, the waste liquid tank 122 is connected to the flow path 113 via the check valve structure 123. In addition, a valve mechanism 114 </ b> A that opens and closes the flow path 113 is provided between the waste liquid tank 122 and the flow path 113.

  Next, the waste liquid tank 122, the check valve structure 123, the flow paths 113A and B connected to the waste liquid tank 122, and the valve mechanism 114A will be specifically described with reference to FIGS.

  First, in a plan view, as shown in FIGS. 7A and 7B, the channel widths of the channels 113A and 113B (the widths of the non-adhered portions forming the channels) are different from each other. Specifically, the non-adhesive portion between the elastic sheets is provided so that the flow path width a in the connection hole 218 of the flow path 113A is narrower than the flow path width b in the connection hole 218 of the flow path 113B.

  As shown in FIG. 7B, the flow path 113B branches into two flow paths with the connection hole 218 as a base point. One of the branched flow paths is connected to the waste liquid tank 122. The other branched flow path is a dead-end flow path with no connection destination. Furthermore, the dead-end channel of the channel 113B is formed so as to cover a part of the channel 113A in plan view. Referring to FIG. 7C, a rectangle composed of the channel width a of the channel 113A and the length c of the dead-end channel is an overlapping portion of the upper and lower channels.

  Here, the channel widths of the channel 113A and the channel 113B are different. Therefore, a relationship of F1> F2 is established between the force F1 required to flow the liquid into the flow path 113A and the force F2 required to flow the liquid into the flow path 113B. This can be understood by considering the case where the channel 113A having the channel width a is expanded by the length L and the case where the channel 113B having the channel width b is expanded by the length L.

  In this case, the fluctuation amount per unit length of the flow path 113A is L / A. On the other hand, the fluctuation amount per unit length of the flow path 113B is L / B. Since the flow path width b> the flow path width a, the fluctuation amount per unit length is larger in the flow path 113A than in the flow path 113B. Therefore, if each of the flow paths 113A and 113B is to be expanded by the same length L, the repulsive force at that time is larger in the flow path 113A. That is, the channel 113B having a wider channel width is more easily expanded than the channel 113A having a narrow channel width.

  In other words, when a pressure necessary for pouring the liquid between the elastic sheets 212 and 213 forming the flow path 113A is applied to the DNA extraction tank 121, the liquid also flows between the elastic sheets 211 and 212. On the other hand, even if the liquid can be poured between the elastic sheets 211 and 212 (even if the flow path 113B can be formed), the liquid cannot be poured between the elastic sheets 212 and 213 with the pressure at that time. In some cases (the flow path 113A may not be formed).

  Next, the front view (sectional view) will be described. FIG. 8A shows a state before the waste liquid flows into the waste liquid tank 122 (before use), and FIG. 8B shows a state when the waste liquid flows into the waste liquid tank 122. FIG. 8C shows a state where the waste liquid flows into the waste liquid tank 122 and the backflow is prevented by the valve mechanism 114A. FIG. 8D shows a state after use in which the closing of the flow paths 113A, B by the valve mechanism 114A is released. A broken line shows the non-adhesion location between elastic sheets.

  As shown in FIG. 8A, the resin plate 215 is partially cut to be provided with a waste liquid tank storage space 216 and a vent 217 that leads from the waste liquid tank storage space 216 to the outside of the microchip 100. A channel 113 </ b> A (also referred to as a first channel) connected to the DNA extraction tank 121 is formed as a non-bonded portion in the first intermediate layer between the elastic sheet 212 and the elastic sheet 213. In addition, the waste liquid tank 122 and the flow path 113B (also referred to as a second flow path) directly connected to the waste liquid tank 122 are formed as non-bonded portions in the second intermediate layer between the elastic sheet 211 and the elastic sheet 212. The The channel 113 </ b> A and the channel 113 </ b> B are connected via a connection hole 218 provided on the elastic sheet 212. Further, a valve mechanism 114 </ b> A for opening and closing the flow path 113 </ b> B is formed as a non-bonded portion in the third intermediate layer between the elastic sheet 213 and the elastic sheet 214.

  As shown in FIG. 8 (B), when the waste liquid flows into the waste liquid tank 122, the non-adhered portions between the elastic sheets are expanded and the flow paths 113A and B and the waste liquid tank 122 are formed. Next, as shown in FIG. 8C, a pressurizing medium is injected so as to spread the non-bonded portion of the elastic sheet forming the valve mechanism 114A. At this time, a part of the flow paths 113 </ b> A and B is crushed upward, and the waste liquid remaining in the flow paths 113 </ b> A and B moves to the waste liquid tank 122. Thereafter, even after the injection of the pressurized medium into the valve mechanism 114A is released after the use of the microchip 100, as shown in FIG. 8D, the portion overlapping the flow path 113A in the flow path 113B is The flow path 113A is crushed downward. This mechanism serves as a check valve that closes the flow path 113A and keeps the waste liquid in the flow path 113B.

  That is, as shown in FIG. 9A, the asymmetry that the flow channel widths of the flow channel 113A and the flow channel 113B are different is caused by the difference in force necessary to form each flow channel (difference in yield pressure). ) To prevent the pressurized liquid from flowing back. That is, the upstream channel width (for example, the channel width a of the channel 113A) when passing the liquid is narrowed, and the downstream channel width (for example, the channel width b of the channel 113B) is widened. By doing so, a backflow prevention structure can be formed inside the microchip 100.

  As described above, in the microchip 100 according to the first embodiment, the backflow of the liquid is prevented by the asymmetry of the channel width between the two channels. Therefore, when the pressure applied to the DNA extraction tank 121 is smaller than the force necessary to form the channel 113A, the pressure was applied even if there was no overlapping portion between the channel 113A and the channel 113B. Liquid backflow can be prevented. That is, by setting the flow path width a of the flow path 113A to be very narrow and the flow path width b of the flow path 113B to be very wide, the backflow of the pressurized liquid can be prevented.

  When a pressure stronger than the state shown in FIG. 9A is applied to the DNA extraction tank 121, the pressurized liquid fills the dead-end channel of the channel 113B. As a result, the area of the elastic sheet 212 corresponding to the overlapping portion of the flow path 113A and the flow path 113B is pushed downward (see FIG. 9B). In response to the elastic sheet 212 of the overlapping portion being pushed downward, the corresponding flow path 113A is also pushed downward.

  Thus, a part of the elastic sheet 212 is pushed down, and the pushed-down elastic sheet 212 functions as a backflow prevention valve. As a result, the pressurized liquid does not flow back into the flow path 113A. Since the width of the waste liquid tank 122 is larger than the flow path width b of the flow path 113B, a force for expanding the flow path 113B is required when the liquid flows from the waste liquid tank 122 to the flow path 113B. .

  Further, the positive pressure in the waste liquid tank housing space 216 generated by the expansion of the waste liquid tank 122 is released by the air in the waste liquid tank housing space 216 being discharged through the vent 217. For this reason, the internal pressure of the waste liquid tank 122 is kept low, and the risk of flowing out of the waste liquid tank 122 into the flow path 113A via the flow path 113B becomes very low. As described above, the check valve structure 123 operates even after the application of the pressurized medium to the valve mechanism 114 is released, that is, after the microchip 100 is removed from the microchip control device 10.

  Returning to FIG. 6, PCR is executed in the PCR tank 124 under the temperature control by the PCR unit 14. Specifically, the flow path from the DNA extraction tank 121 to the PCR tank 124 is branched, and the DNA elution buffer is divided into each PCR tank 124. A primer set is enclosed in the PCR tank 124 in advance, and the DNA elution buffer also contains a reagent such as a polymerase necessary for the PCR reaction. Therefore, the microchip control device 10 can execute PCR if the temperature of the PCR tank 124 is controlled via the PCR unit 14. This temperature control is a temperature control related to the hot start process and the cycle reaction (denature reaction, annealing reaction, and primer extension reaction).

  The weighing tank 125 is a mechanism for weighing the PCR solution containing the amplicon after the PCR reaction. Specifically, the capacity of the weighing tank 125 is smaller than that of the PCR tank 124, and the liquid transport is completed in a state where the PCR solution in the PCR tank 124 has not completely moved to the weighing tank 125. In other words, the microchip control device 10 weighs the PCR solution including the amplicon by leaving a part of the PCR solution in the PCR tank 124.

  As shown in FIG. 10, the electrophoresis unit 126 includes a sample channel 301, a capillary 302, and a polymer tank 303. Specifically, the sample channel 301 is connected to the weighing tank 125 via the electrode tank 304 and is connected to the reservoir 305 at the opposite end. The reservoir 305 is a mechanism for preventing an overflow of the sample flowing into the sample channel 301. The capillary 302 is connected to the polymer tank 303 via the electrode tank 304. The sample channel 301 and the capillary 302 extend in parallel and are connected by a bridge 306 orthogonal to the sample channel 301 and the capillary 302. An electrode attached to the lid 16 is inserted into the electrode tank 304.

  The microchip control apparatus 10 fills the capillary 302 and the bridge 306 with a polymer, performs sample injection, and then executes electrophoresis. At the time of the electrophoresis, the microchip control device 10 monitors the label flowing in the capillary by the electrophoresis unit 15, and displays the detection result showing the change in fluorescence luminance over time via the display unit 25. Output.

  Hereinafter, the flow of processing by the above-described microchip control apparatus 10 will be outlined. FIG. 11 is a flowchart of processing by the microchip control apparatus 10. As shown in FIG. 11, the microchip control apparatus 10 moves the cell lysis buffer to the cell lysis tank 116 to lyse the cells (step S01). Next, the microchip control apparatus 10 moves the cell lysate to the DNA extraction tank 121 and executes a DNA extraction process (step S02). Here, the microchip control device 10 moves the sample residue and the washing buffer to the waste liquid tank. Subsequently, the microchip control device 10 executes a PCR reaction (step S03), weighs the PCR solution (step S04), and executes electrophoresis (step S05).

  As described above, in the microchip 100 of the first embodiment, the residue of the sample and the liquid in contact with the sample are stored in the waste liquid tank 122. Since the waste liquid tank 122 is connected to the flow path 113 via the check valve structure 123, the waste liquid leaks from the waste liquid tank 122 even after the microchip 100 is removed from the microchip control device 10. There is nothing.

  In the first embodiment, it is assumed that direct secondary contamination or secondary infection from the swab 115 or the like when applying a sample to the microchip 100 is prevented by user's consideration. In other words, in the microchip 100 of the first embodiment, a closed system state can be realized if the application port is sealed after the sample is applied, and secondary contamination or secondary infection due to waste liquid from the used microchip 100 can be realized. Is prevented. Such a used microchip 100 can be safely discarded by performing a sterilization process such as an autoclave. Further, in the microchip 100 of the first embodiment, since the gas in contact with the sample is also enclosed in the waste liquid tank 122, it can be applied to a sample having a virus that infects air.

[Second Embodiment]
In 1st Embodiment, the microchip 100 which provided the flow path 113, the valve mechanism 114, and the waste liquid tank 122 as the non-bonding location of the elastic sheets 211-214 was demonstrated. However, even if the microchip 100 is a type in which the resin plates 215 are bonded together, a waste liquid tank can be provided. In such a microchip 100, the flow path 113 and the like can be formed by providing an engraving on the surface of the resin plate 215. The valve mechanism 114 can be realized by providing a physical shutter on the flow path 113, and the liquid movement can be realized by directly extruding the liquid with air or the like.

  Moreover, the waste liquid tank 122 can be realized, for example, by sandwiching an elastic sheet 219 that can be expanded and contracted between resin plates 215 as shown in FIG. 12A shows a state before the waste liquid is injected into the waste liquid tank 122, and FIG. 12B shows a state after the waste liquid is injected into the waste liquid tank 122.

  As shown in FIG. 13, the waste liquid tank 122 can be realized by storing a bag-like member 220 in a waste liquid tank storage space 216. 13A shows a deflated state before the waste liquid is injected into the waste liquid tank 122, and FIG. 13B shows an expanded state after the waste liquid is injected into the waste liquid tank 122.

  Also in the example shown in FIGS. 12 and 13, it is desirable to form a vent 217 that leads from the waste liquid storage space 216 to the outside of the microchip 100.

[Third Embodiment]
In the following, various modifications related to the microchip 100 will be described as the third embodiment. Although the microchip 100 for DNA identification has been described in the first embodiment, a waste liquid tank that realizes a closed system can also be provided in the microchip 100 for other uses. For example, when examining a subject's influenza virus infection by RT-PCR (Real-Time PCR) method, RNA extraction processing, reverse transcription reaction, and RT-PCR may be performed on the microchip 100. . Further, for example, when examining cyanide contamination in river water, ion chromatography (including column operation and detection processing) may be executed on the microchip 100.

  Further, a liquid absorbent material may be enclosed in the waste liquid tank 122 to prevent the waste liquid from flowing. Further, a secondary infection / secondary contamination prevention measure may be taken according to a desired application, such as sealing a sterilizing agent or an oxidizing / reducing agent in the waste liquid tank 122.

  Further, the check valve structure 123 can be formed using a flexible member that is fitted on the flow path so as to be opened when the liquid flows into the waste liquid tank 122, for example. In particular, when forming a flow path by engraving on a plate, unlike the case of forming a flow path by laminating an elastic sheet as in the first embodiment, the flow path is about several millimeters. It may take a width. In this case, a check valve structure 123 having a known mechanism such as a swing type valve or a ball type valve can be applied.

  A part or all of the above embodiments can be described as in the following supplementary notes, but is not limited thereto.

(Appendix 1)
A flow path through which the liquid in contact with the sample flows;
A closed chip waste liquid tank that expands when liquid flows from the flow path.
(Appendix 2)
The microchip according to appendix 1, wherein the closed-system waste liquid tank is formed by an elastic sheet that can be extended.
(Appendix 3)
The microchip according to appendix 1 or 2, wherein the flow path and the closed-system waste liquid tank are formed by providing non-adhesive portions on a plurality of elastic sheets to be laminated and bonded.
(Appendix 4)
The microchip according to appendix 1, wherein the closed-system waste liquid tank is formed of a bag-shaped member.
(Appendix 5)
The closed system waste liquid tank is accommodated in a waste liquid tank storage space provided inside the microchip, and a vent for releasing the positive pressure generated in the waste liquid tank storage space when the closed system waste liquid tank expands The microchip according to any one of appendices 1 to 4, further provided.
(Appendix 6)
The microchip according to any one of supplementary notes 1 to 5, further comprising a check valve structure that prevents backflow of the liquid from the closed waste liquid tank to the flow path.
(Appendix 7)
A cell lysis tank and a DNA extraction tank;
The microchip according to any one of appendices 1 to 6, wherein a residue of a cell sample that has been dissolved in the cell lysis tank and from which DNA has been extracted in the DNA extraction tank is stored in the closed system waste liquid tank.
(Appendix 8)
The microchip according to appendix 7, wherein a washing buffer used for washing DNA in the DNA extraction tank is further stored in the closed system waste liquid tank.
(Appendix 9)
The check valve structure is
A first flow path provided as a non-adhesive spot in a first intermediate layer between a plurality of laminated elastic sheets, and directly connected to the closed waste liquid tank;
Provided as a non-adhesive spot in the second intermediate layer between a plurality of laminated elastic sheets, the channel width is narrower than the first channel, and the closed-system waste liquid passes through the first channel. A second flow path connected to the tank;
The micro of claim 6, wherein the micro is provided on an elastic sheet sandwiched between the first and second intermediate layers, and is formed by a connection hole connecting the first flow path and the second flow path. Chip.
(Appendix 10)
The first channel branches into two channels starting from the connection hole, the one branched channel is a dead-end channel, and a part of the dead-end channel is a part of the dead channel in a plan view. The microchip according to appendix 9, which overlaps with the second flow path.
(Appendix 11)
The microchip according to appendix 6, wherein the check valve structure is formed using a flexible member that is fitted onto the flow path and opens when liquid flows into the closed waste liquid tank.

  The disclosure of the above patent document is incorporated herein by reference. Within the scope of the entire disclosure (including claims) of the present invention, the embodiments and examples can be changed and adjusted based on the basic technical concept. Further, various combinations or selections of various disclosed elements (including each element of each claim, each element of each embodiment or example, each element of each drawing, etc.) within the scope of the claims of the present invention. Is possible. That is, the present invention of course includes various variations and modifications that could be made by those skilled in the art according to the entire disclosure including the claims and the technical idea.

DESCRIPTION OF SYMBOLS 10 Microchip control apparatus 11 Base 12 Table 13 Cell lysis unit 14 PCR unit 15 Electrophoresis unit 16 Lid 17 Pressurization hole 18 Tube 19 Solenoid valve 20 O-ring 21 Accumulator 22 Controller 23 DNA extraction unit 24 Power supply part 25 Display part 100 Microchip 111 Chip body 112 Swab receiving portion 113, 113A, 113B Flow path 114, 114A Valve mechanism 115 Swab (cotton swab)
116 Cell lysis tank 117 Opening part 120 Buffer / reagent tank 121 DNA extraction tank 122 Waste liquid tank 123 Check valve structure 124 PCR tank 125 Weighing tank 126 Electrophoresis part 211-214 Elastic sheet 215 Resin plate 216 Waste liquid tank accommodation space 217 Vent 218 Connection hole 219 Elastic sheet 220 Bag-like member 240 Liquid tank 250 Channel 260, 270 Valve mechanism 301 Sample channel 302 Capillary 303 Polymer tank 304 Electrode tank 305 Reservoir 306 Bridge

Claims (8)

A flow path through which the liquid in contact with the sample flows;
A closed chip waste liquid tank that expands when liquid flows from the flow path.   The microchip according to claim 1, wherein the closed-system waste liquid tank is formed of an elastic sheet that can be extended.   3. The microchip according to claim 1, wherein the flow path and the closed-system waste liquid tank are formed by providing non-adhesive portions on a plurality of elastic sheets to be laminated and bonded.   The microchip according to claim 1, wherein the closed-system waste liquid tank is formed of a bag-shaped member.   The closed system waste liquid tank is accommodated in a waste liquid tank storage space provided inside the microchip, and a vent for releasing the positive pressure generated in the waste liquid tank storage space when the closed system waste liquid tank expands The microchip according to claim 1, further provided.   The microchip according to any one of claims 1 to 5, further comprising a check valve structure for preventing a back flow of the liquid from the closed waste liquid tank to the flow path. A cell lysis tank and a DNA extraction tank;
The microchip according to any one of claims 1 to 6, wherein a residue of a cell sample dissolved in the cell lysis tank and extracted with DNA in the DNA extraction tank is stored in the closed waste liquid tank. .   8. The microchip according to claim 7, wherein the closed waste liquid tank further stores a used washing buffer used for washing DNA in the DNA extraction tank.

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