Inspection Chip

The test chip simplifies flow path switching by using a rotary valve with integrated flow paths, enabling efficient sample handling and nucleic acid recovery while minimizing contamination.

JP7765394B2Active Publication Date: 2025-11-06SEKISUI CHEMICAL CO LTD +1
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Patent Information

Application Number
JP2022551897
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2020-09-28
Filing Date
2021-09-14
Publication Date
2025-11-06
Estimated Expiration
2041-09-14

AI Technical Summary

Technical Problem

Existing test chips with flow path switching structures become overly complex when handling multiple reagents and samples, complicating the analysis process.

Method used

A test chip design featuring a chip body with integrated flow paths and a rotary valve that allows for multiple connection states, enabling simple switching between different flow paths for specimen introduction, adsorption, waste liquid management, and detection, using a rotary valve with connection flow paths that can rotate around a central axis to facilitate seamless transitions between states.

Benefits of technology

The design simplifies the flow channel switching structure, allowing for efficient sample introduction, washing, recovery, and detection processes, enhancing the recovery rate of nucleic acids and reducing contamination risks.

✦ Generated by Eureka AI based on patent content.

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Abstract

Provided is an inspection chip with which it is possible to simplify a complex channel switching structure. An inspection chip 1 comprising: a chip body 2 having a specimen introduction channel, an adsorption channel including an adsorption part, a first waste liquid channel, a recovered liquid introduction channel, and a detection channel including a detection part; and a rotary valve 3 attached to the chip body 2 so as to enable rotation about a rotary axis. The rotary valve 3 has a plurality of connection channels. The plurality of connection channels are positioned so that when the rotary valve 3 rotates about the rotary axis, the rotary valve 3 can assume at least: a first state in which the specimen introduction channel, the adsorption channel, and the first waste liquid channel connect so as to be provided in the stated order from the upstream side; and a second state in which the recovered liquid introduction channel, the adsorption channel, and the detection channel connect so as to be provided in the stated order from the upstream side.
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Description

[Technical Field]

[0001] The present invention relates to a test chip provided with a flow channel switching structure. [Background technology]

[0002] BACKGROUND ART Tests such as blood tests and genetic tests have been attempted by using test chips provided with flow paths through which fluids are delivered, and controlling the delivery and reactions of various specimens or samples.

[0003] For example, Patent Document 1 below discloses a test chip in which a microchannel is provided within a plate-like substrate. The plate-like substrate is provided with a through-hole connected to the microchannel. An external channel means capable of moving on the outer surface of the plate-like substrate is provided. The external channel means has a channel. By moving this external channel means on the surface of the substrate, the connection state between the channel of the external channel means and the through-hole is changed. This switches the channel. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2005-214741 Summary of the Invention [Problem to be solved by the invention]

[0005] In a test chip such as that disclosed in Patent Document 1, when analysis is performed using a plurality of reagents and samples, switching of flow paths becomes even more complicated.

[0006] An object of the present invention is to provide a test chip that can simplify a complicated flow channel switching structure. [Means for solving the problem]

[0007] The test chip of the present invention comprises a chip body having a specimen introduction flow path, an adsorption flow path including an adsorption section, a first waste liquid flow path, a recovery liquid introduction flow path, and a detection flow path including a detection section, and a rotary valve attached to the chip body so as to be rotatable around a rotation axis, wherein the rotary valve has a plurality of connection flow paths, and the plurality of connection flow paths are arranged so that when the rotary valve rotates around the rotation axis, it can assume at least a first state in which the specimen introduction flow path, the adsorption flow path, and the first waste liquid flow path are connected so as to be arranged in this order from the upstream side, and a second state in which the recovery liquid introduction flow path, the adsorption flow path, and the detection flow path are connected so as to be arranged in this order from the upstream side.

[0008] In a specific aspect of the test chip according to the present invention, in the second state, one of the plurality of connecting channels connects the downstream end of the adsorption channel and the upstream end of the detection channel.

[0009] In another specific aspect of the test chip of the present invention, the chip body further has a mixing flow path, and in the second state, the recovery liquid introduction flow path, the adsorption flow path, the mixing flow path, and the detection flow path are connected so as to be arranged in this order from the upstream side.

[0010] In yet another specific aspect of the test chip of the present invention, the chip body further has a second waste liquid flow path, and in the second state, the recovery liquid introduction flow path, the adsorption flow path, the detection flow path, and the second waste liquid flow path are connected so as to be arranged in this order from the upstream side.

[0011] In yet another specific aspect of the test chip of the present invention, the chip body further has an air vent flow path, and in the second state, the recovery liquid introduction flow path, the adsorption flow path, the detection flow path, the second waste liquid flow path, and the air vent flow path are connected so as to be arranged in this order from the upstream side.

[0012] In yet another specific aspect of the test chip of the present invention, the chip body further has a cleaning liquid introduction flow path, and when the rotary valve rotates around the rotation axis, it further has a third state in which the cleaning liquid introduction flow path, the adsorption flow path, and the first waste liquid flow path are connected so that they are arranged in this order from the upstream side, and the multiple connecting flow paths are arranged so that the rotary valve can take at least the first state, the second state, and the third state.

[0013] In yet another specific aspect of the test chip of the present invention, the multiple connection flow paths are arranged so that the rotary valve can take the first state, the third state, and the second state in this order when rotating around the rotation axis.

[0014] In yet another specific aspect of the test chip of the present invention, the rotary valve further has a fourth state in which it seals the upstream and downstream ends of the detection flow path when rotating around the rotation axis, and the multiple connecting flow paths are arranged so that the rotary valve can take the fourth state after the second state.

[0015] In yet another specific aspect of the test chip of the present invention, the rotary valve further has a fifth state in which, when rotating around the rotation axis, it seals the upstream and downstream ends of the detection flow path and seals the upstream and downstream ends of the second waste flow path, and the multiple connecting flow paths are arranged so that the rotary valve can take the fifth state after the second state.

[0016] In yet another specific aspect of the test chip according to the present invention, the adsorption channel is provided at a position overlapping the rotary valve in plan view.

[0017] In yet another specific aspect of the test chip according to the present invention, a hydrophobic filter is connected to a downstream end of at least one of the first waste liquid flow path and the second waste liquid flow path.

[0018] In yet another specific aspect of the test chip according to the present invention, the test chip includes a light-activated gas generating tape that generates gas when irradiated with light, and the liquid is transported by the gas generated from the light-activated gas generating tape. [Effects of the Invention]

[0019] According to the present invention, it is possible to provide a test chip that can simplify a complicated flow channel switching structure. [Brief explanation of the drawings]

[0020] [Figure 1] FIG. 1 is a schematic perspective view showing the appearance of a test chip according to a first embodiment of the present invention. [Figure 2] FIG. 2 is a schematic cross-sectional view of a portion taken along line AA in FIG. [Figure 3] FIG. 3 is a schematic plan view illustrating a flow path in a rotary valve in the test chip according to the first embodiment of the present invention. [Figure 4] FIG. 4 is a schematic perspective view for explaining a flow channel provided in the chip body of the test chip according to the first embodiment of the present invention. [Figure 5] FIG. 5 is a schematic plan view for explaining details of a flow channel provided in the chip body of the test chip according to the first embodiment of the present invention. [Figure 6] FIG. 6 is a schematic plan view for explaining a channel connection state in a first state of the test chip according to the first embodiment of the present invention. [Figure 7] FIG. 7 is a schematic plan view for explaining the channel connection state in the third state of the test chip according to the first embodiment of the present invention. [Figure 8] FIG. 8 is a schematic plan view illustrating a channel connection state in a second state of the test chip according to the first embodiment of the present invention. [Figure 9] FIG. 9 is a schematic plan view for explaining the channel connection state in the fourth state of the test chip according to the first embodiment of the present invention. [Figure 10]FIG. 10 is a schematic cross-sectional view for explaining a liquid delivery method using a light-generating gas tape. [Figure 11] FIG. 11 is a schematic plan view for explaining the first mixing channel used in the test chip according to the first embodiment of the present invention. [Figure 12] FIG. 12 is a schematic plan view illustrating the second mixing channel used in the test chip according to the first embodiment of the present invention. [Figure 13] FIG. 13 is a schematic plan view for explaining the detection channel used in the test chip according to the first embodiment of the present invention. [Figure 14] FIG. 14 is a schematic plan view illustrating a flow path in a rotary valve in a test chip according to a second embodiment of the present invention. [Figure 15] FIG. 15 is a schematic plan view illustrating a flow path in a chip body of a test chip according to a second embodiment of the present invention. [Figure 16] FIG. 16 is a schematic plan view for explaining the channel connection state in the first state of the test chip according to the second embodiment of the present invention. [Figure 17] FIG. 17 is a schematic plan view for explaining the channel connection state in the third state of the test chip according to the second embodiment of the present invention. [Figure 18] FIG. 18 is a schematic plan view illustrating a channel connection state in a second state of the test chip according to the second embodiment of the present invention. [Figure 19] FIG. 19 is a schematic plan view for explaining the channel connection state in the fourth state of the test chip according to the second embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0021] The present invention will be clarified below by describing specific embodiments of the present invention with reference to the drawings.

[0022] [First embodiment] (Configuration of the test chip) Fig. 1 is a schematic perspective view showing the appearance of a test chip according to a first embodiment of the present invention, and Fig. 2 is a schematic cross-sectional view of a portion taken along line AA in Fig. 1.

[0023] The test chip 1 comprises a chip body 2 and a rotary valve 3. The chip body 2 has a rectangular plate-like shape, although this is not particularly limited. The chip body 2 has a first surface 2a and a second surface 2b facing the first surface 2a. On the first surface 2a side, the rotary valve 3 is attached to the chip body 2 so as to be rotatable around a central axis which is the axis of rotation.

[0024] Chip body 2 has substrate 4 and sealing sheet 5 laminated on substrate 4. Substrate 4 is made of an appropriate material such as synthetic resin. The surface of substrate 4 opposite sealing sheet 5 is first surface 2a of chip body 2. The outer surface of sealing sheet 5 is second surface 2b of chip body 2. Sealing sheet 5 is made of an appropriate sheet such as a synthetic resin sheet.

[0025] A first flow path 6, a second flow path 7, and a third flow path 8 are provided in the substrate 4. The first flow path 6, the second flow path 7, and the third flow path 8 are open to the first surface 2a. The first flow path 6, the second flow path 7, and the third flow path 8 extend in a direction connecting the first surface 2a and the second surface 2b.

[0026] A groove provided on the lower surface of the substrate 4 is sealed to provide an adsorption section 9. Inside the adsorption section 9, an adsorption body 9A is housed.

[0027] An end of the first flow path 6 opposite to the end that opens to the first surface 2a is connected to the adsorption unit 9. An end of the second flow path 7 opposite to the end that opens to the first surface 2a is connected to the adsorption unit 9. As a result, the adsorption unit 9 is connected between the first flow path 6 and the second flow path 7. In this embodiment, the adsorption unit 9, the first flow path 6, and the second flow path 7 form an adsorption flow path 11.

[0028] The rotary valve 3 is attached to the substrate 4 so as to be rotatable around a central axis, that is, a rotation axis B. The first flow path 6 is provided so as to include the rotation axis B. Preferably, the central axis of the first flow path 6 coincides with the rotation axis B.

[0029] Furthermore, a groove provided on the lower surface of the substrate 4 is sealed to provide a fourth flow path 10. The fourth flow path 10 is connected to the end of the third flow path 8 opposite to the end that opens to the first surface 2a of the chip body 2. The fourth flow path 10 extends away from the rotation axis B in the radial direction of the rotary valve 3. In this embodiment, the third flow path 8 and the fourth flow path 10 constitute a specimen introduction flow path, a recovery liquid introduction flow path, or a washing liquid introduction flow path. Note that in FIG. 2, the fourth flow path 10 is arranged in the same line as the adsorption unit 9 for convenience of explanation. However, in this embodiment, the fourth flow path 10 constituting the specimen introduction flow path, the recovery liquid introduction flow path, or the washing liquid introduction flow path is not arranged in the same line as the adsorption unit 9. However, the fourth flow path 10 may be arranged in the same line as the adsorption unit 9.

[0030] 3 is a schematic plan view illustrating the flow paths within the rotary valve in the test chip according to the first embodiment of the present invention. A first connection flow path 12 and a plurality of second connection flow paths 13-15 are provided on the lower surface 3a of the rotary valve 3. The first connection flow path 12 and the second connection flow paths 13-15 are configured by providing grooves of the shape shown in the figure on the lower surface 3a of the rotary valve 3. As shown in FIG. 2, these grooves are sealed by the first surface 2a of the chip body 2, thereby configuring the first connection flow path 12 and the second connection flow path 13. Note that while FIG. 2 shows only the second connection flow path 13, the other second connection flow paths 14-15 are configured in the same manner.

[0031] As shown in FIG. 2 , one end of the first connecting flow path 12 extends to the portion where the rotation axis B is present and is connected to the first flow path 6. The first connecting flow path 12 extends from the rotation axis B of the rotary valve 3 radially outward of the rotary valve 3. In this case, the first connecting flow path 12 is linear; however, the first connecting flow path 12 may have other planar shapes, such as a curved, meandering, or L-shaped shape. Therefore, the first connecting flow path 12 is not limited to extending from the rotation axis B to the radially outward side of the rotary valve 3, as long as it extends outward from the rotation axis B. In FIG. 2 , the radially outer end of the first connecting flow path 12 is connected to the third flow path 8. However, by rotating the rotary valve 3 around the rotation axis B, the radially outer end of the first connecting flow path 12 can also be connected to other flow paths.

[0032] The second connection flow path 13 is provided at a position separated from the first connection flow path 12 and separated from the rotation axis B. In the state shown in FIG. 2 , the second connection flow path 13 is connected to the second flow path 7. By rotating the rotary valve 3 around the rotation axis B, the second flow path 7 can be connected to other second connection flow paths 14-15 within the rotary valve 3. Alternatively, instead of the second connection flow path 13, other second connection flow paths 14-15 can be connected to the second flow path 7, etc. within the chip body 2.

[0033] FIG. 4 is a schematic perspective view illustrating the flow paths provided in the chip body of the test chip according to the first embodiment of the present invention. On the first surface 2a of the chip body 2, a rotary valve 3 is attached at the position indicated by the dashed line C. Within the region where the rotary valve 3 is attached, one ends of a first flow path 6, a second flow path 7, and a third flow path 8 open on the first surface 2a. As indicated by the dashed lines, the first flow path 6, the second flow path 7, and the third flow path 8 extend from the first surface 2a of the chip body 2 toward the second surface 2b. An adsorption unit 9 is connected between the first flow path 6 and the second flow path 7. The end of the third flow path 8 opposite to the end opening on the first surface 2a is connected to the fourth flow path 10 described above.

[0034] 1, 2, and 4, the chip body 2 is provided with a specimen introduction flow path 21, a waste fluid flow path 22, a washing liquid introduction flow path 23, a recovery liquid introduction flow path 24, a mixing flow path 25, a detection flow path 26, and a vent flow path 27, as shown in FIG. 5. The chip body 2 is provided with a plurality of the fourth flow paths 10, each of which constitutes the specimen introduction flow path 21, the washing liquid introduction flow path 23, and the recovery liquid introduction flow path 24. Alternatively, the fourth flow path 10 may be connected to the specimen introduction flow path 21, the washing liquid introduction flow path 23, and the recovery liquid introduction flow path 24.

[0035] By rotating the rotary valve 3 around the rotation axis B, the first connection flow path 12 can be connected to a specimen introduction flow path 21, a cleaning liquid introduction flow path 23, and a recovery liquid introduction flow path 24. In addition, the second connection flow paths 13 to 15 can be connected to a waste liquid flow path 22 and a mixing flow path 25.

[0036] In the test chip 1, a plurality of connection channels are arranged so that when the rotary valve 3 rotates around the rotation axis B, the test chip 1 can assume at least the following first state and second state.

[0037] The first state is a state in which the specimen introduction flow path 21, the adsorption flow path 11, and the waste flow path 22 are connected in this order from the upstream side. In this embodiment, the specimen introduction flow path 21 and the adsorption flow path 11 are connected by a first connection flow path 12. Furthermore, the adsorption flow path 11 and the waste flow path 22 are connected by a second connection flow path 13.

[0038] The second state is a state in which the recovery liquid introduction flow path 24, the adsorption flow path 11, and the detection flow path 26 are connected in this order from the upstream side. In this embodiment, the recovery liquid introduction flow path 24 and the adsorption flow path 11 are connected by a first connection flow path 12. A mixing flow path 25 is provided between the adsorption flow path 11 and the detection flow path 26, and the adsorption flow path 11 and the mixing flow path 25 are connected by a second connection flow path 15. In this embodiment, a waste liquid flow path 22 is connected downstream of the detection flow path 26. Furthermore, a vent flow path 27 is connected downstream of the waste liquid flow path 22. However, the mixing flow path 25 and the vent flow path 27 do not necessarily have to be provided. The waste liquid flow path 22 does not necessarily have to be connected downstream of the detection flow path 26.

[0039] By rotating the rotary valve 3 and switching between the first state and the second state in this order, for example, nucleic acid extracted from a specimen using an extraction liquid can be adsorbed onto the adsorbent 9A, recovered, and subjected to a test such as PCR (Polymerase Chain Reaction) within the test chip 1. Furthermore, the test chip 1 of this embodiment can be applied to various reaction tests and tests that require the same or similar liquid delivery steps by using an appropriate adsorbent and detection method.

[0040] In this embodiment, the rotary valve 3 is configured to rotate around the rotation axis B so as to be able to assume at least the first state and the second state. In this case, the rotary valve 3 may be configured to be able to assume a third state, a fourth state, etc. in addition to the first and second states. For example, the rotary valve 3 may be configured to implement a third state in which a cleaning liquid is allowed to flow between the first state in which a sample is allowed to flow and the second state in which a recovery liquid is allowed to flow. Furthermore, the rotary valve 3 may be configured to implement a fourth state in which at least the upstream end and downstream end of the detection flow channel 26 are sealed.

[0041] In this embodiment, a plurality of connection flow paths are formed by one first connection flow path 12 and three second connection flow paths 13 to 15. However, in the present invention, a plurality of first connection flow paths may be provided. The number of first connection flow paths may be, for example, 1 or more and 3 or less. The number of second connection flow paths may be, for example, 1 or more and 10 or less. Furthermore, the total number of all the plurality of connection flow paths may be, for example, 2 or more and 13 or less.

[0042] (How to use the test chip) An example of how to use the test chip 1 will be described with reference to FIGS.

[0043] 6 is a schematic plan view illustrating the channel connection state of the test chip according to the first embodiment of the present invention in a first state. The rotary valve 3 is rotated to connect the specimen introduction channel 21, the adsorption channel 11, and the waste channel 22 in this order, as shown in FIG. 6. In this embodiment, the specimen introduction channel 21 and the adsorption channel 11 are connected by a first connection channel 12. The adsorption channel 11 and the waste channel 22 are connected by a second connection channel 13. In addition, a vent channel 27 is connected downstream of the waste channel 22.

[0044] In the first state, a specimen can be introduced into the adsorption flow path 11 through the specimen introduction flow path 21, and the specimen can be supplied to the adsorption flow path 11. Then, waste liquid reaches the waste liquid flow path 22 and is discharged. Examples of specimens include body fluids, viruses, bacteria, cells, and extracts thereof. The adsorption flow path 11 has an adsorption unit 9 shown in FIG. 2, which contains an adsorbent 9A for adsorbing nucleic acids extracted from the specimen with an extracting liquid, for example.

[0045] Next, the rotary valve 3 is rotated clockwise to enter the third state. FIG. 7 is a schematic plan view illustrating the flow path connection state of the test chip according to the first embodiment of the present invention in the third state. Here, the cleaning liquid introduction flow path 23, the adsorption flow path 11, and the waste liquid flow path 22 are connected in this order. In particular, in this embodiment, the cleaning liquid introduction flow path 23 and the adsorption flow path 11 are connected by a first connection flow path 12. The adsorption flow path 11 and the waste liquid flow path 22 are connected by a second connection flow path 14. In addition, a vent flow path 27 is connected downstream of the waste liquid flow path 22.

[0046] In the third state, the washing liquid can be supplied to the adsorption flow path 11 by introducing the washing liquid from the washing liquid introduction flow path 23. The waste liquid then reaches the waste liquid flow path 22 and is discharged. The washing liquid supplied to the adsorption flow path 11 can wash the nucleic acid adsorbed to the adsorbent 9A.

[0047] Next, the rotary valve 3 is rotated clockwise to enter the second state. FIG. 8 is a schematic plan view illustrating the channel connection state of the test chip according to the first embodiment of the present invention in the second state. Here, the recovery liquid introduction channel 24, the adsorption channel 11, and the detection channel 26 are connected in this order. In particular, in this embodiment, the recovery liquid introduction channel 24 and the adsorption channel 11 are connected by a first connection channel 12. The adsorption channel 11 and the detection channel 26 are connected by a second connection channel 15.

[0048] In the second state, the recovery liquid can be supplied to the adsorption flow path 11 by introducing the recovery liquid from the recovery liquid introduction flow path 24. The recovery liquid can recover, for example, nucleic acids adsorbed to the adsorbent 9A, and the recovered nucleic acids can be supplied to the detection flow path 26. The waste liquid then reaches the waste liquid flow path 22 and is discharged. The detection flow path 26 has a detection unit, and can perform a reaction such as PCR using the supplied nucleic acids, etc. Note that, for example, water can be used as the recovery liquid.

[0049] In this embodiment, in the second state, a mixing channel 25 is provided between the second connection channel 15 and the detection channel 26. In the mixing channel 25, for example, a recovery liquid containing nucleic acids and a reaction reagent that is sent later can be merged and mixed. Thereafter, the mixed liquid can be supplied to the detection channel 26, and testing can be performed. For example, a PCR reaction reagent can be used as the reaction reagent.

[0050] In this embodiment, the waste liquid flow path 22 is connected to the downstream side of the detection flow path 26. Furthermore, the vent flow path 27 is connected to the downstream side of the waste liquid flow path 22.

[0051] As described above, in the test chip 1, the flow path within the test chip 1 can be switched between the first state and the second state by rotating the rotary valve 3 around the rotation axis B. Therefore, with a relatively simple structure, the introduction, washing, recovery, reaction, etc. of the sample can be performed.

[0052] Furthermore, by switching and washing the flow path within the test chip 1 so that a third state can be established between the first state and the second state, the recovery rate of nucleic acids can be further increased.

[0053] The rotary valve 3 may be rotated clockwise to enter the fourth state. Fig. 9 is a schematic plan view illustrating the channel connection state of the test chip according to the first embodiment of the present invention in the fourth state. In the fourth state, the upstream and downstream ends of the detection channel 26, the upstream and downstream ends of the mixing channel 25, and the upstream and downstream ends of the waste channel 22 are sealed.

[0054] When the waste liquid flow path 22 is provided as in this embodiment, the upstream and downstream ends of the detection flow path 26 can be sealed. In this case, the outflow of the reaction product to the outside can be further suppressed. Furthermore, by sealing the upstream and downstream ends of the mixing flow path 25, contamination can be further suppressed. Furthermore, when the vent flow path 27 is provided as in this embodiment, the upstream and downstream ends of the waste liquid flow path 22 can be sealed. In this case, the outflow of the waste liquid to the outside can be more reliably suppressed.

[0055] (other details) flow path; In the present invention, the dimensions of each channel are not particularly limited, but it is preferable that the channel be a microchannel. Here, a microchannel refers to a minute channel that generates a micro effect when transporting a fluid. In such a microchannel, the fluid is strongly affected by surface tension and behaves differently from a fluid flowing through a normal large-dimensional channel.

[0056] The cross-sectional shape and size of the microchannel are not particularly limited as long as the micro-effect is generated. For example, when a pump or gravity is used to flow a fluid through the microchannel, in order to further reduce the flow channel resistance, if the cross-sectional shape of the microchannel is roughly rectangular (including square), the dimension of the smaller side is preferably 20 μm or more, more preferably 50 μm or more, and even more preferably 100 μm or more. Furthermore, in order to further miniaturize the microfluidic device, the dimension is preferably 5 mm or less, more preferably 1 mm or less, and even more preferably 500 μm or less.

[0057] Furthermore, when the cross-sectional shape of the microchannel is approximately circular, the diameter (minor axis in the case of an ellipse) is preferably 20 μm or more, more preferably 50 μm or more, and even more preferably 100 μm or more. From the viewpoint of further miniaturizing the microfluidic device, the diameter (minor axis in the case of an ellipse) is preferably 5 mm or less, more preferably 1 mm or less, and even more preferably 500 μm or less.

[0058] On the other hand, for example, when flowing a fluid through a microchannel, in order to more effectively utilize capillary action, if the cross-sectional shape of the microchannel is approximately rectangular (including square), the dimension of the smaller side is preferably 5 μm or more, more preferably 10 μm or more, and even more preferably 20 μm or more. Also, the dimension of the smaller side is preferably 200 μm or less, and more preferably 100 μm or less.

[0059] Fluid delivery; Any suitable liquid delivery device can be used to deliver the specimen, cleaning solution, or recovery solution. Among these, it is preferable to use a photo-induced gas generating tape that generates gas when irradiated with light.

[0060] FIG. 10 is a schematic cross-sectional view illustrating a liquid delivery method using a light-emitting gas generating tape. As shown in FIG. 10, in this embodiment, the fourth flow paths 10, which constitute the specimen introduction flow path 21, the cleaning liquid introduction flow path 23, and the recovery liquid introduction flow path 24, are open on the first surface 2a. A light-emitting gas generating tape 31 is attached to the first surface 2a so as to seal the openings. Therefore, the light-emitting gas generating tape 31 is disposed upstream of the fourth flow paths 10, which constitute the specimen introduction flow path 21, the cleaning liquid introduction flow path 23, and the recovery liquid introduction flow path 24. The light-emitting gas generating tape 31 generates gas when irradiated with light. The generated gas can be used to deliver the specimen, cleaning liquid, or recovery liquid. By delivering liquid using the light-emitting gas generating tape 31 provided within the test chip 1, external contamination can be further suppressed.

[0061] Adsorbents; An adsorbent 9A is housed in the adsorption section 9 in the adsorption flow path 11 shown in Fig. 2. The adsorbent 9A can be used in the form of, for example, a membrane, a filter, a plate, a fiber, a tube, particles, a porous material, or the like. The adsorbent 9A can be made of, for example, silicon compounds, phosphate minerals, silicate minerals, aluminosilicate minerals, or the like. Among these, the adsorbent 9A is preferably made of silica fiber or glass fiber.

[0062] mixing channel; The mixing channel 25 is not particularly limited, and may be, for example, the first mixing channel shown in FIG. 11 . The first mixing channel 32 is a channel for merging and mixing, for example, a recovery solution containing nucleic acids with a reaction reagent that is subsequently delivered. The first mixing channel 32 has a zigzag structure in a plan view. Furthermore, in the first mixing channel 32, the channel depth is deeper in the shaded areas. Specifically, in the first mixing channel 32, first channel sections 32a having a relatively deep channel depth and second channel sections 32b having a relatively shallow channel depth are repeatedly and alternately provided. The first channel section 32a extends in a first direction X1, bends at a first bend section 32c, and connects to the second channel section 32b. The second channel section 32b extends in a second direction X2, bends at a second bend section 32d, and connects to the first channel section 32a. The first bent portion 32c and the second bent portion 32d are bent portions that bend the flow path and also change the depth of the flow path. In this way, a first mixing flow path 32 having a planar zigzag structure with repeated height differences is configured. By providing the first mixing flow path 32 having a planar zigzag structure with repeated height differences, multiple liquids can be mixed with even greater precision.

[0063] Alternatively, a second mixing channel shown in FIG. 12 may be used.

[0064] In this embodiment, the second mixing flow path 33 has a first flow path section 33a and a second flow path section 33b. The first flow path section 33a is a recessed section in which the flow path is expanded toward one side surface of the test chip 1. The second flow path section 33b is a recessed section in which the flow path is expanded toward the other side surface of the test chip 1. Furthermore, the first flow path section 33a and the second flow path section 33b are provided alternately in order starting from the first flow path section 33a. In this way, by providing the first flow path section 33a and the second flow path section 33b alternately, multiple liquids can be mixed with even greater precision.

[0065] The first mixing channel 32 and the second mixing channel 33 may be used either alone or in combination.

[0066] detection flow channel; The detection channel 26 is a channel having a detection section for performing PCR etc. Fig. 13 is a schematic plan view showing a channel structure as an example of the detection channel.

[0067] As shown in FIG. 13, the detection flow path 41 has a main flow path 42. One ends of a plurality of branch flow paths 43 to 45 are connected to the main flow path 42. The branch flow paths 43 to 45 are provided as reaction vessels for carrying out reactions such as PCR. Flow path resistance portions 46 to 48, each having a smaller cross-sectional area than the branch flow paths 43 to 45, are provided at the ends of the branch flow paths 43 to 45 opposite to the end connected to the main flow path 42. One end of the branch flow paths 43 to 45 is an inflow end that opens to the main flow path 42. The other end of the branch flow paths 43 to 45 is an outflow end that is connected to the flow path resistance portions 46 to 48.

[0068] The downstream ends of the flow path resistance portions 46 to 48 are connected to a connecting flow path 49. The connecting flow path 49 is connected to the main flow path 42.

[0069] A sub-branch flow path 50 is connected to the main flow path 42 between adjacent branch flow paths 43, 44. A sub-branch flow path 51 is also connected to the main flow path 42 between adjacent branch flow paths 44, 45. The sub-branch flow paths 50, 51 have inflow ends connected to the main flow path 42, but do not have gas outflow ports. The inflow ends of the sub-branch flow paths 50, 51 open to the main flow path 42.

[0070] By providing the sub-branch channel 50, it is possible to suppress contamination of specimens and reagents between the branch channels 43 and 44. The sub-branch channel 51 can also suppress contamination between the branch channels 44 and 45 that are adjacent to each other.

[0071] Therefore, by providing the detection flow path 41 shown in FIG. 13, contamination can be further suppressed.

[0072] Hydrophobic filters; A hydrophobic filter may be provided at the downstream end of the waste liquid flow path. For example, a polytetrafluoroethylene (PTFE) filter can be used as the hydrophobic filter. By providing a hydrophobic filter, it is possible to more reliably prevent the waste liquid from leaking out.

[0073] Examples of commercially available hydrophobic filters include PF-020, PF-040, PF-050, and PF-060 (all manufactured by Advantec Co., Ltd.).

[0074] [Second embodiment] (Configuration of the test chip) Fig. 14 is a schematic plan view illustrating a flow path in a rotary valve in a test chip according to a second embodiment of the present invention, and Fig. 15 is a schematic plan view illustrating a flow path in a chip body in a test chip according to the second embodiment of the present invention.

[0075] 14, a first connection flow path 72 and a plurality of second connection flow paths 73 to 75 are provided on the lower surface 63a of the rotary valve 63. The first connection flow path 72 and the second connection flow paths 73 to 75 are configured on the lower surface 63a of the rotary valve 63 in the same manner as in the first embodiment.

[0076] As shown in FIG. 15, the chip body 62 is provided with a specimen introduction flow path 81, a first waste liquid flow path 82a, a cleaning liquid introduction flow path 83, a recovery liquid introduction flow path 84, a detection flow path 86, and a second waste liquid flow path 82b.

[0077] As in the first embodiment, by rotating the rotary valve 63 around the rotation axis, the first connection flow path 72 can be connected to a specimen introduction flow path 81, a cleaning liquid introduction flow path 83, and a recovery liquid introduction flow path 84. In addition, the second connection flow paths 73 to 75 can be connected to a first waste liquid flow path 82a, a second waste liquid flow path 82b, and a detection flow path 86.

[0078] In the test chip according to the second embodiment, multiple connection flow paths are also arranged so that when the rotary valve 63 rotates around the rotation axis, it can assume at least the first state and the second state described below.

[0079] The first state is a state in which the specimen introduction flow path 81, the adsorption flow path 71, and the first waste liquid flow path 82a are connected in this order from the upstream side. In this embodiment, the specimen introduction flow path 81 and the adsorption flow path 71 are connected by a first connection flow path 72. Furthermore, the adsorption flow path 71 and the first waste liquid flow path 82a are connected by a second connection flow path 73.

[0080] The second state is a state in which the recovery liquid introduction flow path 84, the adsorption flow path 71, and the detection flow path 86 are connected in this order from the upstream side. In this embodiment, the recovery liquid introduction flow path 84 and the adsorption flow path 71 are connected by a first connection flow path 72. The adsorption flow path 71 and the detection flow path 86 are connected by a second connection flow path 75. In this embodiment, no mixing flow path is provided between the second connection flow path 75 and the detection flow path 86. A second waste liquid flow path 82b is connected downstream of the detection flow path 86. However, no vent flow path is connected downstream of the second waste liquid flow path 82b.

[0081] By rotating the rotary valve 63 and performing the first state and the second state in this order, for example, nucleic acid extracted from a specimen using an extraction liquid can be adsorbed onto an adsorbent within the test chip according to the second embodiment, recovered, and subjected to a reaction such as PCR.

[0082] In this embodiment, the rotary valve 63 is configured to rotate about a rotation axis so as to be able to assume at least the first and second states. In this case, the rotary valve 63 may be configured to be able to assume a third state, a fourth state, etc. in addition to the first and second states. For example, the rotary valve 63 may be configured to implement a third state in which a cleaning liquid is allowed to flow between the first state in which a specimen is allowed to flow and the second state in which a recovery liquid is allowed to flow. Furthermore, the rotary valve may be configured to implement a fourth state in which at least the upstream and downstream ends of the detection flow channel 86 are sealed.

[0083] (How to use the test chip) An example of a method of using the test chip according to the second embodiment will be described with reference to FIGS.

[0084] 16 is a schematic plan view illustrating the channel connection state of the test chip according to the second embodiment of the present invention in a first state. The rotary valve 63 is rotated to connect the specimen introduction channel 81, the adsorption channel 71, and the first waste fluid channel 82a in this order, as shown in FIG. 16. In this embodiment, the specimen introduction channel 81 and the adsorption channel 71 are connected by a first connection channel 72. The adsorption channel 71 and the first waste fluid channel 82a are connected by a second connection channel 73.

[0085] In the first state, the sample can be introduced into the adsorption flow path 71 by introducing the sample through the sample introduction flow path 81. The waste liquid then reaches the first waste liquid flow path 82a and is discharged. The adsorption flow path 71 has an adsorption section, and the adsorption section contains, for example, an adsorbent for adsorbing nucleic acids extracted from the sample by the extraction liquid.

[0086] Next, the rotary valve 63 is rotated counterclockwise to enter the third state. Figure 17 is a schematic plan view for explaining the flow path connection state of the test chip according to the second embodiment of the present invention in the third state. Here, the cleaning liquid introduction flow path 83, the adsorption flow path 71, and the first waste liquid flow path 82a are connected in this order. In particular, in this embodiment, the cleaning liquid introduction flow path 83 and the adsorption flow path 71 are connected by the first connection flow path 72. The adsorption flow path 71 and the first waste liquid flow path 82a are connected by the second connection flow path 74.

[0087] In the third state, the washing liquid can be supplied to the adsorption flow path 71 by introducing the washing liquid from the washing liquid introduction flow path 83. The waste liquid then reaches the first waste liquid flow path 82a and is discharged. The washing liquid supplied to the adsorption flow path 71 can wash the nucleic acid adsorbed to the adsorbent.

[0088] Next, the rotary valve 3 is rotated counterclockwise to enter the second state. FIG. 18 is a schematic plan view illustrating the channel connection state of the test chip according to the second embodiment of the present invention in the second state. Here, the recovery liquid introduction channel 84, the adsorption channel 71, and the detection channel 86 are connected in this order. In particular, in this embodiment, the recovery liquid introduction channel 84 and the adsorption channel 71 are connected by a first connection channel 72. The adsorption channel 71 and the detection channel 86 are connected by a second connection channel 75. In addition, a second waste liquid channel 82b is connected downstream of the detection channel 86.

[0089] In the second state, the recovery liquid can be supplied to the adsorption flow path 71 by introducing the recovery liquid from the recovery liquid introduction flow path 84. The nucleic acid adsorbed to the adsorbent can be recovered by the recovery liquid, and the recovered nucleic acid can be supplied to the detection flow path 86. The waste liquid then reaches the second waste liquid flow path 82b and is discharged. The detection flow path 86 has a detection unit, and can perform a reaction such as PCR using the supplied nucleic acid, etc.

[0090] In the test chip according to the second embodiment, as described above, the flow path in the test chip can be switched between the first state and the second state by rotating the rotary valve 63 around the rotation axis, so that the test chip can be operated in a relatively simple structure, allowing for sample introduction, washing, recovery, testing, and the like.

[0091] Furthermore, by switching and washing the flow path within the test chip so that a third state can be established between the first and second states, the recovery rate of nucleic acids can be further increased.

[0092] The rotary valve 63 may be further rotated counterclockwise to enter the fourth state. FIG. 19 is a schematic plan view illustrating the channel connection state of the test chip according to the second embodiment of the present invention in the fourth state. In the fourth state, the upstream and downstream ends of the detection channel 86 are sealed. By providing the first waste liquid channel 82a and the second waste liquid channel 82b as in this embodiment, the upstream and downstream ends of the detection channel 86 can be sealed. In this case, the outflow of reaction products to the outside can be further suppressed.

[0093] The matters described in the first embodiment can be similarly applied to the second embodiment, for example, the configurations described in other details in the first embodiment can be applied.

[0094] In the second embodiment, a first waste liquid flow path 82a, which is used after the specimen or cleaning liquid has been delivered, and a second waste liquid flow path 82b, which is used after the recovery liquid has been delivered, are provided separately. In this case, it is possible to prevent air from being trapped between the waste liquid after the specimen or cleaning liquid has been delivered and the waste liquid after the recovery liquid has been delivered, thereby enabling the test chip to be made smaller. However, as in the first embodiment, the first waste liquid flow path 82a and the second waste liquid flow path 82b may be the same waste liquid flow path. [Explanation of symbols]

[0095] 1...Test chip 2,62...Chip body 2a, 2b...first and second faces 3,63...Rotary valve 3a,63a…bottom surface 4...Substrate 5...Sealing sheet 6, 7, 8...1st, 2nd, 3rd flow paths 9...Adsorption part 9A…Adsorbent 10...Fourth flow path 11,71...Adsorption channel 12, 72...First connecting flow path 13~15, 73~75...Second connecting flow path 21, 81...Sample introduction channel 22...Waste fluid flow path 23, 83...Cleaning liquid introduction channel 24, 84...Recovery liquid introduction channel 25…Mixing channel 26, 41, 86...Detection channel 27...Ventilation channel 31...Light gas generating tape 32, 33...First and second mixing channels 32a, 33a...first flow path section 32b, 33b...second flow path section 32c, 32d...First and second bends 41...Detection flow path 42…Main channel 43, 44, 45...Branch flow path 46, 47, 48...Flow resistance section 49...Connecting channel 50, 51...Sub-branch flow path 82a, 82b...First and second waste liquid flow paths

Claims

1. a chip body having a specimen introduction flow path, an adsorption flow path including an adsorption unit, a first waste liquid flow path, a recovery liquid introduction flow path, and a detection flow path including a detection unit; a rotary valve attached to the tip body so as to be rotatable about a rotation axis; Equipped with the rotary valve has a plurality of connecting flow paths; When the rotary valve rotates around the rotation axis, a first state in which the specimen introduction flow path, the adsorption flow path, and the first waste liquid flow path are connected so as to be provided in this order from the upstream side; a second state in which the recovery liquid introduction flow path, the adsorption flow path, and the detection flow path are connected so as to be provided in this order from the upstream side; The plurality of connecting flow paths are arranged so as to at least When the rotary valve rotates around the rotation axis, a fourth state in which the upstream end and the downstream end of the detection channel are sealed; The test chip, wherein the plurality of connecting channels are arranged so that the rotary valve can assume the fourth state after the second state.

2. 2. The test chip according to claim 1, wherein in the second state, the downstream end of the adsorption channel and the upstream end of the detection channel are connected by one of the plurality of connection channels.

3. the chip body further has a mixing channel; The test chip according to claim 1 , wherein in the second state, the recovery liquid introduction channel, the adsorption channel, the mixing channel, and the detection channel are connected in this order from the upstream side.

4. the chip body further has a second waste liquid flow path; The test chip according to any one of claims 1 to 3, wherein in the second state, the recovery liquid introduction flow path, the adsorption flow path, the detection flow path, and the second waste liquid flow path are connected so as to be arranged in this order from the upstream side.

5. the tip body further having a vent channel; 5. The test chip according to claim 4, wherein in the second state, the recovery liquid introduction flow path, the adsorption flow path, the detection flow path, the second waste liquid flow path, and the vent flow path are connected in this order from the upstream side.

6. the chip body further has a cleaning solution introduction channel; When the rotary valve rotates around the rotation axis, a third state in which the cleaning liquid introduction flow path, the adsorption flow path, and the first waste liquid flow path are connected to each other so as to be provided in this order from the upstream side; 6. The test chip according to claim 1, wherein the plurality of connecting flow paths are arranged so that the rotary valve can take at least the first state, the second state, and the third state.

7. When the rotary valve rotates around the rotation axis, The test chip according to claim 6 , wherein the plurality of connection channels are arranged so as to be capable of taking the first state, the third state, and the second state in this order.

8. When the rotary valve rotates around the rotation axis, a fifth state in which the upstream and downstream ends of the detection flow path are sealed, and the upstream and downstream ends of the second waste flow path are sealed; 6. The test chip according to claim 4, wherein the plurality of connecting channels are arranged so that the rotary valve can take the fifth state after the second state.

9. 9. The test chip according to claim 1, wherein the adsorption channel is provided at a position overlapping the rotary valve in a plan view.

10. 10. The test chip according to claim 1, wherein a hydrophobic filter is connected to a downstream end of the first waste liquid flow path.

11. An inspection chip described in any one of claims 4, 5, and 8, wherein a hydrophobic filter is connected to the downstream end of the second waste liquid flow path.

12. 12. The test chip according to claim 1, further comprising a light-activated gas generating tape that generates gas when irradiated with light, wherein liquid is delivered by the gas generated from the light-activated gas generating tape.

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