Microdevice and method for manufacturing the same
The microdevice addresses liquid leakage issues by employing symmetrically arranged closed spaces to enhance substrate bonding with atmospheric pressure, ensuring robust adhesion and preventing clogging without external vacuum conduits.
Patent Information
- Application Number
- JP2021131053
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2021-08-11
- Publication Date
- 2026-02-12
- Estimated Expiration
- 2041-08-11
AI Technical Summary
Existing microdevices face issues with liquid leakage from microchannels due to insufficient bonding between PDMS and opposing substrates, which can be exacerbated by hydrophilic treatment, and the use of negative pressure conductions can lead to clogging and increased chip dimensions.
A microdevice design featuring symmetrically arranged closed spaces on either side of microchannels, bonded using atmospheric pressure, which suppresses liquid leakage by ensuring firm adhesion between substrates without the need for external vacuum conduits.
The design effectively prevents liquid leakage from microchannels by ensuring robust bonding between substrates, maintaining structural integrity and reducing the risk of clogging, while also minimizing chip size.
Smart Images

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Abstract
Description
[Technical Field]
[0001] FIELD OF THE DISCLOSURE The present disclosure relates to microdevices and methods for manufacturing microdevices. [Background technology]
[0002] As an immunoassay method using fluorescence, a fluorescence polarization immunoassay (FPIA) that detects a substance to be measured by utilizing an antigen-antibody reaction is known. For example, Patent Document 1 discloses a method for determining the concentration of a measurement antigen (substance to be measured) from the polarization degree of the measured fluorescence.
[0003] Furthermore, microdevices used for analyzing biological substances are known. For example, Patent Document 2 discloses a biological molecule microarray in which biological molecules are held between a first member and a second member, and a plurality of grooves are formed in parallel on the surface of either the first member or the second member that comes into contact with the other member, thereby providing a plurality of spaces that serve as reaction regions.
[0004] The substrates constituting microdevices used in analyzing biological materials generally consist of a substrate made of polydimethylsiloxane (hereinafter referred to as the PDMS substrate) and an opposing substrate made of glass, quartz, or the like. The PDMS substrate and the quartz glass substrate are easily bonded by the adhesive force of the PDMS substrate. However, for example, when a hydrophilically treated PDMS substrate is used, the adhesive force of the PDMS substrate is weakened by the hydrophilic treatment, which may cause the solution to leak from the flow path of the microdevice.
[0005] Therefore, Patent Document 3 discloses a microchip in which a continuous, annular negative pressure conduit is provided near the outer periphery of the bonding surface of the PDMS substrate, in order to vacuum-adsorb the PDMS substrate to the opposing substrate. In the microchip of Patent Document 3, the inside of the negative pressure conduit is evacuated and sucked before use of the microchip, thereby increasing the bonding strength between the PDMS substrate and the opposing substrate. [Prior art documents] [Patent documents]
[0006] [Patent Document 1] Japanese Patent Application Publication No. 3-103765 [Patent Document 2] Japanese Patent Application Laid-Open No. 2005-30927 [Patent Document 3] Patent No. 3918040 Summary of the Invention [Problem to be solved by the invention]
[0007] In the microchip of Patent Document 3, air is exhausted from a single continuous negative pressure conduit, which may clog the conduit due to atmospheric pressure, preventing sufficient air exhaust. Furthermore, since the negative pressure conduit is provided on the outer edge of the microchip, there is a risk that the PDMS substrate and the opposing substrate may not be bonded sufficiently around the flow channel located in the center of the microchip, and the external dimensions of the microchip are increased. Furthermore, after exhausting air from the negative pressure conduit, it is necessary to block the exhaust port of the negative pressure conduit.
[0008] The present disclosure has been made in view of the above circumstances, and aims to provide a microdevice that can suppress liquid leakage from a microchannel and a method for manufacturing the microdevice. [Means for solving the problem]
[0009] In order to achieve the above object, a microdevice according to a first aspect of the present disclosure comprises: a first substrate; a second substrate bonded to the first substrate and having at least one groove portion forming at least one microchannel together with the first substrate, and a plurality of recesses forming a plurality of independent closed spaces together with the first substrate; the at least one microchannel has a hole for filling or discharging a measurement target solution or a calibration curve solution into or from the at least one microchannel, a first portion extending in a predetermined direction within a measurement region where the measurement target solution or the calibration curve solution is irradiated with light, and a second portion connecting the hole and the first portion; When viewed in plan, the plurality of independent closed spaces two of the closed spaces are arranged symmetrically with the first portion in between, and two other of the plurality of independent closed spaces are arranged symmetrically with the second portion in between, When viewed from above, the two closed spaces sandwiching the first portion have shapes symmetrical with respect to the first portion as an axis of symmetry, and the other two closed spaces sandwiching the second portion have shapes symmetrical with respect to the second portion as an axis of symmetry, Each of the plurality of independent closed spaces bonds the first substrate and the second substrate together in a depressurized state, and does not have a hole for depressurizing.
[0010] A method for manufacturing a microdevice according to a second aspect of the present disclosure includes: a preparation step of preparing a first substrate; a forming step of forming a second substrate having at least one groove portion which forms at least one microchannel together with the first substrate, and a plurality of recesses which are positioned on either side of the at least one groove portion and which form a plurality of independent closed spaces together with the first substrate; a bonding step of bonding the first substrate and the second substrate to form the at least one microchannel and the plurality of independent closed spaces; a decompression step of placing the bonded first substrate and the second substrate in a vacuum chamber and reducing the pressure inside the vacuum chamber to reduce the pressure inside the formed plurality of independent closed spaces, the at least one microchannel has a hole for filling or discharging a measurement target solution or a calibration curve solution into or from the at least one microchannel, a first portion extending in a predetermined direction within a measurement region where the measurement target solution or the calibration curve solution is irradiated with light, and a second portion connecting the hole and the first portion; When viewed in a plane, two of the plurality of independent closed spaces are arranged symmetrically with the first portion in between, and the other two of the plurality of independent closed spaces are arranged symmetrically with the second portion in between, When viewed from above, the two closed spaces sandwiching the first portion have shapes symmetrical with respect to the first portion as an axis of symmetry, and the other two closed spaces sandwiching the second portion have shapes symmetrical with respect to the second portion as an axis of symmetry, Each of the plurality of independent closed spaces bonds the first substrate and the second substrate together in a depressurized state, and does not have a hole for depressurizing. [Effects of the Invention]
[0011] According to the present disclosure, leakage of liquid from a microchannel can be suppressed. [Brief explanation of the drawings]
[0012] [Figure 1] FIG. 1 is a top view showing a microdevice according to a first embodiment. [Figure 2] FIG. 2 is a cross-sectional view of the microdevice shown in FIG. 1 taken along line AA. [Figure 3] FIG. 2 is a plan view showing a second substrate according to the first embodiment. [Figure 4] 3 is a schematic diagram showing grooves and recesses according to the first embodiment. FIG. [Figure 5] 10 is a diagram showing the relationship between the angle of the bottom of the recess with respect to the first main surface of the first substrate, the thickness of the bottom of the recess, and 1 / 2 of the width of the recess, according to the first embodiment. FIG. [Figure 6] 1 is a flowchart showing a method for manufacturing a microdevice according to the first embodiment. [Figure 7] 5A to 5C are schematic views for explaining a forming step of a second substrate according to the first embodiment. [Figure 8] FIG. 10 is a schematic diagram showing a microdevice according to a second embodiment. [Figure 9] 10 is a flowchart showing a method for manufacturing a microdevice according to a second embodiment. DETAILED DESCRIPTION OF THE INVENTION
[0013] Microdevices according to embodiments will be described below with reference to the drawings.
[0014] <Embodiment 1> A microdevice 10 according to this embodiment will be described with reference to Figures 1 to 7. The microdevice 10 is used, for example, to detect a substance to be measured using fluorescence polarization immunoassay.
[0015] As shown in Fig. 1, the microdevice 10 includes a first substrate 20, a second substrate 30, three microchannels 52, 54, and 56, and a plurality of closed spaces 62a, 62b, 64a, 64b, 66a, and 66b. For ease of understanding, in this specification, the rightward direction of the microdevice 10 in Fig. 1 (to the right on the paper) is referred to as the +X direction, the upward direction (upward on the paper) is referred to as the +Y direction, and the direction perpendicular to the +X and +Y directions (toward the viewer on the paper) is referred to as the +Z direction. Furthermore, the microchannels 52, 54, and 56 are collectively referred to as microchannel 50, and the closed spaces 62a to 66b are collectively referred to as closed spaces 60.
[0016] The first substrate 20 of the microdevice 10 is a flat quartz glass substrate. As shown in FIG. 2, the first substrate 20 has a first main surface 20a and a second main surface 20b opposite the first main surface 20a. A second substrate 30 is bonded to the first main surface 20a of the first substrate 20. In addition, excitation light EL in a fluorescence polarization immunoassay is irradiated onto a measurement region S shown in FIG. 1, and the excitation light EL is perpendicularly incident on the second main surface 20b of the first substrate 20.
[0017] The second substrate 30 of the microdevice 10 is made of a material with low autofluorescence. In this embodiment, the second substrate 30 is made of a copolymer of polydimethylsiloxane containing carbon black and polyethylene glycol. The second substrate 30 of this embodiment has hydrophilic properties due to the polyether groups contained in the copolymer.
[0018] 2, the second substrate 30 has a first main surface 30a and a second main surface 30b opposite to the first main surface 30a. In this embodiment, the first main surface 30a of the second substrate 30 is bonded to the first main surface 20a of the first substrate 20.
[0019] 3, three grooves 32, 34, and 36 are formed on the first main surface 30a of the second substrate 30, which together with the first substrate 20 (first main surface 20a) form a microchannel 50. Furthermore, at both ends of each of the grooves 32, 34, and 36, a through-hole 37 is provided which corresponds to an inlet or outlet of the microchannel 50. Furthermore, recesses 42a, 42b, 44a, 44b, 46a, and 46b are formed on the first main surface 30a of the second substrate 30, which together with the first substrate 20 (first main surface 20a) form a closed space 60.
[0020] The centers of grooves 32, 34, and 36 extend parallel to the X direction within measurement region S. Groove 32 is located in the center of second substrate 30 in the XY plane, and both ends also extend in the X direction. Groove 34 is located on the +Y side in the XY plane, and both ends are bent toward the +Y side. Groove 36 is located on the -Y side in the XY plane, and both ends are bent toward the -Y side.
[0021] The recesses 42a and 42b form a pair and have the same shape. The recesses 42a and 42b are located symmetrically across the grooves 32, 34, and 36 in the measurement region S in the width direction of the grooves 32, 34, and 36. The recesses 44a and 44b form a pair and have the same shape. The recess 44a is located between the +X side end of the groove 32 and the +X side end of the groove 34, and the recess 44b is located between the +X side end of the groove 32 and the +X side end of the groove 36. The recesses 44a and 44b are located symmetrically across the groove 32 in the width direction of the groove 32. The recesses 46a and 46b form a pair and have the same shape. Recess 46a is located between the -X side end of groove 32 and the -X side end of groove 34, and recess 44b is located between the -X side end of groove 32 and the -X side end of groove 36. Recess 46a and recess 46b are located symmetrically across groove 32 in the width direction of groove 32.
[0022] Each of the microchannels 52, 54, and 56 of the microdevice 10 is formed by the first substrate 20 (first main surface 20a) and the grooves 32, 34, and 36 of the second substrate 30. As shown in FIG. 1 , the microchannels 52, 54, and 56, like the grooves 32, 34, and 36, extend parallel to the X direction within the measurement region S. Both ends of the microchannel 54 are bent toward the +Y side, and both ends of the microchannel 56 are bent toward the −Y side. The width of the microchannel 50 within the measurement region S (i.e., its length in the Y direction) is, for example, 200 μm. A solution to be measured, a calibration curve solution, etc. are filled into or discharged from the microchannel 50 via the through-holes 37.
[0023] The calibration curve solution is used to create a calibration curve (i.e., a calibration curve between the degree of polarization and the concentration of the substance to be measured) in fluorescence polarization immunoassay. The calibration curve solution contains the substance to be measured at different predetermined concentrations, an antibody at a predetermined concentration, and a fluorescently labeled derivative at a predetermined concentration. The measurement solution is a solution that is to be measured in fluorescence polarization immunoassay. The measurement solution contains the substance to be measured, the concentration of which is unknown, and an antibody and a fluorescently labeled derivative at the same concentrations as those in the calibration curve solution.
[0024] The substance to be measured may be any compound that can be detected by immunoassay using fluorescence. Examples of substances to be measured include antibiotics, physiologically active substances, and mycotoxins. Specific examples of substances to be measured include prostaglandin E2, β-lactoglobulin, chloramphenicol, and deoxyribonucleic acid. Bare Nol and others.
[0025] Antibodies specifically bind to the substance to be measured through an antigen-antibody reaction. Antibodies can be obtained, for example, by inoculating the substance to be measured into a host animal (e.g., a mouse or a cow), and then collecting and purifying the antibodies produced in the blood of the host animal. Commercially available antibodies can also be used.
[0026] A fluorescently labeled derivative is a derivative obtained by fluorescently labeling a substance to be measured. The fluorescently labeled derivative specifically binds to an antibody in competition with the substance to be measured through an antigen-antibody reaction. The fluorescently labeled derivative can be obtained by binding a fluorescent substance to the substance to be measured using a known method. The fluorescent substance is fluorescein or rhodamine β.
[0027] The closed spaces 62a to 66b of the microdevice 10 are formed by the first substrate 20 (first main surface 20a) and the recesses 42a to 46b of the second substrate 30, respectively. 1, the closed spaces 62a and 62b have the same shape and are positioned symmetrically across the microchannel 50 in the measurement region S in the width direction of the microchannel 50. In this embodiment, the closed spaces 62a and 62b are in a depressurized state, and the bottoms 47 of the recesses 42a and 42b that form the closed spaces 62a and 62b are recessed toward the first substrate 20 (in the −Z direction) due to atmospheric pressure, as shown in FIG.
[0028] In this embodiment, the closed spaces 62a, 62b are depressurized, so that the bottoms 47 of the recesses 42a, 42b are recessed by atmospheric pressure, and the second substrate 30 is pressed against the first substrate 20 by the atmospheric pressure. Therefore, in the microdevice 10, the second substrate 30 is firmly bonded to the first substrate 20 by the adsorptive force of the second substrate 30 and the atmospheric pressure. Since the first substrate 20 and the second substrate 30 are firmly bonded by the adsorptive force of the second substrate 30 and the atmospheric pressure, the microdevice 10 can suppress liquid leakage from the microchannel 50 formed by the grooves 32, 34, 34 of the first substrate 20 and the second substrate 30. Furthermore, the closed spaces 62a, 62b have the same shape and are located symmetrically across the microchannel 50, so that the second substrate 30 is pressed evenly against the first substrate 20.
[0029] The closed spaces 64a and 64b have the same shape and are positioned symmetrically on the +X side across the width of the microchannel 52. The closed spaces 66a and 66b also have the same shape and are positioned symmetrically on the -X side across the width of the microchannel 52. Like the closed spaces 62a and 62b, the closed spaces 64a to 66b are also in a depressurized state, and the bottoms 47 of the recesses 44a to 46b are recessed toward the first substrate 20 (in the -Z direction) due to atmospheric pressure. Therefore, because the closed spaces 64a to 66b are in a depressurized state, the second substrate 30 is further pressed against the first substrate 20, and the microdevice 10 can suppress liquid leakage from the microchannel 50.
[0030] Here, the width (length in the Y direction) of the recess 42a that forms the closed space 62a together with the first substrate 20 and the thickness of the bottom 47 of the recess 42a will be described. Note that the closed spaces 62a and 62b have the same shape and are positioned symmetrically across the microchannel 50 in the measurement region S in the width direction of the microchannel 50, and therefore the recess 42b that forms the closed space 62b is also similar to the recess 42a.
[0031] As shown in FIG. 4 , if the width of recess 42a is 2×L, the thickness of bottom 47 of recess 42a is d, the depth (length in the Z direction) of groove 34 is h, the atmospheric pressure is P, the tension applied to bottom 47 of recess 42a is T, the Young's modulus of second substrate 30 is E, and the angle of bottom 47 relative to first main surface 20a of first substrate 20 at midpoint M of bottom 47 is θ, the balance of forces at midpoint M is expressed by the following formula (1). Furthermore, since the deflection ε of bottom 47 is expressed as (1 / cos θ)−1, the tension T is expressed by the following formula (2). The depth h of groove 34 is expressed by the following formula (3). A force of L×P is applied to connection point N between bottom 47 of recess 42a and the sidewall of groove 34 in the direction toward first substrate 20 (−Z direction), pressing second substrate 30 against first substrate 20.
[0032]
number
number
number
[0033] Furthermore, equation (4) is obtained from equations (1) and (2), and equation (5) is obtained from equation (3). The thickness d of the bottom 47 is expressed by equation (6) from equations (4) and (5).
[0034]
number
number
number
[0035] Atmospheric pressure P is 0.1013N / mm 2 and the Young's modulus E of the second substrate 30 is 2 N / mm 2Assuming that the depth h of the microchannel 50 is 0.9 mm, the relationship between the angle θ, the thickness d of the bottom 47, and L, which is half the width of the recess 42a, is expressed from equations (6) and (5) as shown in Fig. 5. Generally, from the standpoint of ease of processing the second substrate 30 and the strength of the second substrate 30, it is preferable that the thickness d of the bottom 47 be 1 mm or more and 3 mm or less. Therefore, as shown in Fig. 5, it is preferable that L, which is half the width of the recess 42a, be 1.9 mm or more and 2.5 mm or less, i.e., the width 2 × L of the recess 42a be 3.8 mm or more and 5.0 mm or less.
[0036] Next, a method for manufacturing the microdevice 10 will be described with reference to Figures 6 and 7. Figure 6 is a flowchart showing the method for manufacturing the microdevice 10. The method for manufacturing the microdevice 10 includes a preparation step (step S10) of preparing a first substrate 20, a formation step (step S20) of forming a second substrate 30, a bonding step (step S30) of bonding the first substrate 20 and the second substrate 30 to form a microchannel 50 and a closed space 60, and a depressurization step (step S40) of depressurizing the inside of the formed closed space 60. The second substrate 30 has grooves 32, 34, and 36 that, together with the first substrate 20, form the microchannel 50. The second substrate 30 also has recesses 42a and 42b positioned symmetrically across the grooves 32, 34, and 36 in the measurement area S and forming closed spaces 62a and 62b together with the first substrate 20, recesses 44a and 44b positioned symmetrically across the +X side end of the groove 32 and forming closed spaces 64a and 64b together with the first substrate 20, and recesses 46a and 46b positioned symmetrically across the -X side end of the groove 32 and forming closed spaces 66a and 66b together with the first substrate 20.
[0037] In step S10, a first substrate 20 is prepared. In this embodiment, the first substrate 20 is a flat quartz glass substrate.
[0038] In step S20, first, a resin mixture containing carbon black, polydimethylsiloxane resin, polyethylene glycol, and a curing agent is prepared. Next, as shown in FIG. 7, a mold 82 corresponding to the shape of second substrate 30 is placed in a mold frame 84. The prepared resin mixture is then poured into mold frame 84, and the resin mixture poured into mold frame 84 is cured. After the cured resin mixture is peeled from mold 82 and mold frame 84, through-holes 37 are formed at predetermined positions in the cured resin mixture using a jig. In this way, second substrate 30 is formed, having grooves 32, 34, 36 and recesses 42a to 46b on first main surface 30a, and having through-holes 37 formed therein. Note that mold 82 is fabricated by photolithography processing a silicon substrate.
[0039] 6, in step S30, the first substrate 20 is placed on the first main surface 30a of the second substrate 30, and then the first substrate 20 is pressed against the second substrate 30. As a result, the first substrate 20 and the second substrate 30 are bonded together by the adsorptive force of the second substrate 30, and the microchannel 50 and the closed space 60 are formed.
[0040] In step S40, the bonded first substrate 20 and second substrate 30 are placed in a vacuum chamber, and the vacuum chamber is evacuated and depressurized. This allows air in the closed space 60 to be evacuated through the small gap between the first substrate 20 and the second substrate 30, reducing the pressure in the closed space 60. Next, the vacuum chamber is returned to atmospheric pressure, and the bonded first substrate 20 and second substrate 30 are removed. When the vacuum chamber is returned to atmospheric pressure, air is less likely to flow into the depressurized closed space 60. Therefore, the bottoms 47 of the recesses 42a-46b, which together with the first substrate 20 form the depressurized closed space 60, are depressed by atmospheric pressure, and the second substrate 30 is pressed against the first substrate 20 by atmospheric pressure. Therefore, in the microdevice 10, the first substrate 20 and the second substrate 30 are firmly bonded together by the suction force of the second substrate 30 and the atmospheric pressure. In this manner, the microdevice 10 can be fabricated.
[0041] Next, we will explain how to use the microdevice 10. The microdevice 10 is used, for example, in immunoassay of a measurement target substance (detection of the measurement target substance).
[0042] In immunoassay of a target substance, first, each of the three target solutions is filled into each of the microchannels 52, 54, and 56 of the microdevice 10 using a micropipette. In the microdevice 10, the first substrate 20 and the second substrate 30 are firmly bonded together by the adsorptive force of the second substrate 30 and atmospheric pressure, which prevents leakage of the target solutions from the microchannel 50. Each of the three target solutions contains a target substance of unknown concentration, an antibody, and a fluorescently labeled derivative.
[0043] Next, the microdevice 10 filled with the solution to be measured is set in an apparatus for measuring the degree of polarization of fluorescence (fluorescence polarization measuring apparatus), and the degree of polarization of the fluorescence emitted from the solution to be measured is measured. The concentration of the substance to be measured contained in the solution to be measured can be determined from the measured degree of polarization and a calibration curve prepared in advance.
[0044] As described above, in the microdevice 10, the closed space 60 is decompressed, so that the first substrate 20 and the second substrate 30 are firmly bonded together by the suction force of the second substrate 30 and atmospheric pressure, thereby preventing liquid leakage from the microchannel 50. Furthermore, since the closed spaces 60 are positioned symmetrically in the width direction of the microchannel 50, the first substrate 20 and the second substrate 30 can be bonded together uniformly.
[0045] <Embodiment 2> The microdevice 10 may be vacuum packaged (vacuum packed). As shown in FIG. 8, a microdevice 10A of the present embodiment includes the microdevice 10 of embodiment 1 and a packaging body 90. In the present embodiment, the microdevice 10 of embodiment 1 (i.e., the first substrate 20 and the second substrate 30 that have been joined together and the pressure inside the closed space 60 has been reduced) is vacuum packaged in the packaging body 90. Here, a method for manufacturing the packaging body 90 and the microdevice 10A will be described.
[0046] The packaging body 90 accommodates the microdevice 10 of embodiment 1 in a state where the inside is decompressed, and seals the microdevice 10 of embodiment 1. The packaging body 90 is, for example, a vacuum bag in which the outermost layer is formed from nylon and the innermost layer is formed from polyethylene.
[0047] 9 is a flowchart showing a method for manufacturing microdevice 10A. The method for manufacturing microdevice 10A includes a preparation step (step S10) of preparing first substrate 20, a formation step (step S20) of forming second substrate 30, a bonding step (step S30) of bonding first substrate 20 and second substrate 30 to form microchannel 50 and closed space 60, a depressurization step (step S40) of depressurizing the inside of the formed closed space 60, and a packaging step (step S50) of vacuum-packaging first substrate 20 and second substrate 30 in a state where the bonded closed space 60 has been depressurized. Since the preparation step (step S10) to the depressurization step (step S40) are the same as those in embodiment 1, only the packaging step (step S50) will be described here.
[0048] In step S50, first, the first substrate 20 and the second substrate 30 (i.e., the microdevice 10 of embodiment 1) that have been joined together and whose closed space 60 has been decompressed are housed inside a package 90 that has three sides sealed, and the pressure inside the package 90 is reduced from one open side. After the pressure reduction is complete, the open side is sealed by heat sealing to hermetically seal the first substrate 20 and the second substrate 30 that have been joined together and whose closed space 60 has been decompressed. In this way, the microdevice 10A can be manufactured.
[0049] In this embodiment, the first substrate 20 and the second substrate 30 are vacuum-packaged after being joined together and the closed space 60 is depressurized, so that the depressurized state of the closed space 60 can be maintained for a long period of time, and the microdevice 10 can be stored for a long period of time. Furthermore, the microdevice 10 can be used immediately by simply opening the package 90.
[0050] <Modification> Although the embodiments have been described above, various modifications can be made to the present disclosure without departing from the spirit and scope of the present disclosure.
[0051] The material constituting the first substrate 20 is not limited to quartz. The first substrate 20 may be formed from glass (including quartz glass) with low autofluorescence, synthetic resin, or the like. The second substrate 30 may be formed from polydimethylsiloxane that does not have hydrophilic properties and contains carbon black. Furthermore, the second substrate 30 may be formed from a synthetic resin other than polydimethylsiloxane.
[0052] The second substrate 30 of the first embodiment has hydrophilic properties due to the polyether groups of the copolymer that constitutes the second substrate 30. The second substrate 30 may be made hydrophilic by subjecting the surface to hydrophilic treatment after being formed from polydimethylsiloxane containing carbon black.
[0053] In the first embodiment, the microdevice 10 has three microchannels 52, 54, and 56, and the second substrate 30 has three grooves 32, 34, and 36, but the numbers of microchannels and grooves are not limited to three. It is sufficient for the microdevice 10 to have at least one microchannel, and for the second substrate 30 to have at least one groove.
[0054] Furthermore, the microdevice 10 may include a pair of closed spaces 62a, 62b arranged symmetrically with the microchannels 52, 54, 56 in the measurement region S sandwiched therebetween. The second substrate 30 may include recesses 42a, 42b arranged symmetrically with the grooves 32, 34, 36 in the measurement region S sandwiched therebetween.
[0055] In the first embodiment, the closed spaces 62a and 62b (recesses 42a and 42b) are positioned symmetrically across the microchannel 50 (grooves 32, 34, 36) in the measurement region S in the width direction of the microchannel 50 (grooves 32, 34, 36). The closed spaces 62a and 62b (recesses 42a and 42b) only need to sandwich the microchannel 50 (grooves 32, 34, 36) in the width direction of the microchannel 50 (grooves 32, 34, 36), and the closed spaces 62a and 62b (recesses 42a and 42b) do not have to be arranged symmetrically. Furthermore, the closed spaces 64a and 64b (recesses 44a and 44b) and the closed spaces 66a and 66b (recesses 46a and 46b) do not have to be arranged symmetrically either. That is, the closed spaces 60 (recesses 42a to 46b) do not have to be arranged symmetrically.
[0056] Furthermore, the closed spaces 62a and 62b (recesses 42a and 42b) are not limited to having the same shape. The closed spaces 64a and 64b (recesses 44a and 44b) and the closed spaces 66a and 66b (recesses 46a and 46b) are not limited to having the same shape either.
[0057] In the first embodiment, the closed space 60 of the microdevice 10 is depressurized, but the closed space 60 does not have to be depressurized. In this case, the closed space 60 of the microdevice 10 is depressurized before the solution is filled into the microchannel 50.
[0058] The microdevice 10 is not limited to fluorescence polarization immunoassay and may be used for other purposes.
[0059] Although the preferred embodiments have been described above, the present disclosure is not limited to such specific embodiments, and the present disclosure includes the inventions described in the claims and their equivalents. [Explanation of symbols]
[0060] 10, 10A microdevice, 20 first substrate, 20a first main surface, 20b second main surface, 30 second substrate, 30a first main surface, 30b second main surface, 32, 34, 36 groove portion, 37 through-hole, 42a, 42b, 44a, 44b, 46a, 46b recess, 47 bottom of recess, 50, 52, 54, 56 microchannel, 60, 62a, 62b, 64a, 64b, 66a, 66b closed space, 82 mold, 84 mold frame, 90 package, EL excitation light, d thickness of bottom of recess, E Young's modulus, h depth of groove portion, L 1 / 2 width of recess, M midpoint of bottom of recess, N connection point between bottom of recess and side wall of groove portion, P atmospheric pressure, S measurement area, T tension, ε deflection, θ Angle of the bottom of the recess with respect to the first main surface of the first substrate 20
Claims
1. a first substrate; a second substrate bonded to the first substrate and having at least one groove portion forming at least one microchannel together with the first substrate, and a plurality of recesses forming a plurality of independent closed spaces together with the first substrate; the at least one microchannel has a hole for filling or discharging a measurement target solution or a calibration curve solution into or from the at least one microchannel, a first portion extending in a predetermined direction within a measurement region where the measurement target solution or the calibration curve solution is irradiated with light, and a second portion connecting the hole and the first portion; When viewed in a plan view, two of the plurality of independent closed spaces are arranged symmetrically with the first portion in between, and the other two of the plurality of independent closed spaces are arranged symmetrically with the second portion in between, When viewed from above, the two closed spaces sandwiching the first portion have shapes symmetrical with respect to the first portion as an axis of symmetry, and the other two closed spaces sandwiching the second portion have shapes symmetrical with respect to the second portion as an axis of symmetry, each of the plurality of independent closed spaces bonds the first substrate and the second substrate together in a depressurized state and does not have a hole for depressurization; Microdevices.
2. A packaging body is provided, the first substrate and the second substrate are vacuum-packaged in the packaging body; The microdevice of claim 1 .
3. The length of the recess in the width direction of the microchannel is 3.8 mm or more and 5 mm or less. The microdevice according to claim 1 or 2.
4. the first substrate is made of glass; the second substrate is formed from polydimethylsiloxane; The microdevice according to claim 1 .
5. a preparation step of preparing a first substrate; a forming step of forming a second substrate having at least one groove portion which forms at least one microchannel together with the first substrate, and a plurality of recesses which are positioned on either side of the at least one groove portion and which form a plurality of independent closed spaces together with the first substrate; a bonding step of bonding the first substrate and the second substrate to form the at least one microchannel and the plurality of independent closed spaces; a decompression step of placing the bonded first substrate and the second substrate in a vacuum chamber and reducing the pressure inside the vacuum chamber to reduce the pressure inside the formed plurality of independent closed spaces, the at least one microchannel has a hole for filling or discharging a measurement target solution or a calibration curve solution into or from the at least one microchannel, a first portion extending in a predetermined direction within a measurement region where the measurement target solution or the calibration curve solution is irradiated with light, and a second portion connecting the hole and the first portion; When viewed in a plan view, two of the plurality of independent closed spaces are arranged symmetrically with the first portion in between, and the other two of the plurality of independent closed spaces are arranged symmetrically with the second portion in between, When viewed from above, the two closed spaces sandwiching the first portion have shapes symmetrical with respect to the first portion as an axis of symmetry, and the other two closed spaces sandwiching the second portion have shapes symmetrical with respect to the second portion as an axis of symmetry, each of the plurality of independent closed spaces bonds the first substrate and the second substrate together in a depressurized state and does not have a hole for depressurization; Microdevice manufacturing method.
6. a packaging step of vacuum-packaging the first substrate and the second substrate that are joined together and in a state where the independent closed spaces are decompressed, The method for manufacturing a microdevice according to claim 5 .
Citation Information
Patent Citations
Immunoassay with fluorescent polarization by using immobilized antibody or antigen
JP1991103765A
Organism-related molecule microarray
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Microchip and lamination method of PDMS substrate and counter substrate
JP2005249540A
Fine flow channel structure and its manufacturing method
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Microchip and method for manufacturing microchip
JP2013113679A