Functional device and method of manufacturing the same
10207264 ยท 2019-02-19
Assignee
Inventors
Cpc classification
B81C1/00119
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/12
PERFORMING OPERATIONS; TRANSPORTING
B81B2201/058
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502707
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0816
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/161
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/12
PERFORMING OPERATIONS; TRANSPORTING
B01L2400/0415
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01L3/00
PERFORMING OPERATIONS; TRANSPORTING
B81C1/00
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A functional device (and a functional device manufacturing method) includes a first substrate in which a groove is formed in one surface, a second substrate which is integrally disposed by bonding one surface of the second substrate to the one surface of the first substrate, and forms a flow path together with the groove of the first substrate, at least one modification object of a capture body which captures a target substance supplied into the flow path, an electrode which imparts an electrical or a chemical action to the target substance, and a catalyst, in which the modification object is disposed by being modified on a part of an inner surface of the flow path, a bonding portion between the one surface of the first substrate and the one surface of the second substrate is formed by bonding fluorine to silica.
Claims
1. A functional device, comprising: a first substrate which has a groove formed on one surface of the first substrate; a second substrate which is integrally disposed with the first substrate by bonding one surface of the second substrate and the one surface of the first substrate, and forms a flow path together with the groove of the first substrate; and one of a capture body which is configured to capture a target substance supplied into the flow path, an electrode which is configured to impart an electrical or a chemical action to the target substance, and a catalyst, in which the one is disposed on a part of an inner surface of the flow path, wherein each of the first substrate and the second substrate is a glass substrate, a bonding portion between the one surface of the first substrate and the one surface of the second substrate includes FSi bonds where fluorine is bonded to silica included in at least one substrate, and said bonding portion between the one surface of the first substrate and the one surface of the second substrate has a fluorine concentration of greater than or equal to 0.6 at % and less than or equal to 3.5 at %.
2. The functional device according to claim 1, wherein the flow path is a fine flow path of a microscale or a nanoscale.
3. The functional device according to claim 1, wherein a bonding strength of the bonding portion is greater than or equal to 0.5 J/m.sup.2.
4. The functional device according to claim 1, wherein the bonding portion is formed to have pressure resistance performance in which a sample solution is not leaked even when a pressure of the sample solution including the target substance which is pressurized and supplied to the flow path is 2000 kPa.
5. The functional device according to claim 1, wherein the capture body is formed of a silane coupling agent.
6. A method of manufacturing a functional device, comprising: forming a groove on one surface of a first substrate; arranging at least one of a capture body which is configured to capture a target substance supplied into the flow path, an electrode which is configured to impart an electrical or a chemical action to the target substance, and a catalyst in a position corresponding to an inner surface of the flow path which is formed of the groove and one surface of a second substrate at the time of bonding the first substrate and the second substrate; exposing oxygen plasma and supplying fluorine to at least one of the one surface of the first substrate and the one surface of the second substrate, and adjusting hydrophilic properties of the one surface; and a step of bonding the one surface of the first substrate and the one surface of the second substrate forming a bonding portion while maintaining a temperature at which the capture body, electrode or catalyst is not thermally damaged, the bonding portion between the one surface of the first substrate and the one surface of the second substrate including FSi bonds where fluorine is bonded to silica included in at least one substrate, and the bonding portion between the one surface of the first substrate and the one surface of the second substrate having a fluorine concentration of greater than or equal to 0.6 at % and less than or equal to 3.5 at % wherein each of the first substrate and the second substrate is a glass substrate.
7. The method of manufacturing the functional device according to claim 6, wherein the flow path is a fine flow path of a microscale or a nanoscale.
8. The method of manufacturing the functional device according to claim 6, wherein a contact angle of water in at least any one of the one surface of the first substrate and the one surface of the second substrate before being joined is from 10 degrees to 50 degrees.
9. The method of manufacturing the functional device according to claim 6, wherein the temperature is 25 C. to 100 C.
10. The method of manufacturing the functional device according to claim 6, wherein the capture body is formed of a silane coupling agent.
11. A method of detecting a target substance by using the functional device according to claim 1, comprising: injecting a sample solution including a target substance into the flow path; and detecting a target substance captured in the flow path.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE INVENTION
(11) Hereinafter, a functional device and a functional device manufacturing method according to one embodiment of the present invention will be described with reference to
(12) As illustrated in
(13) Further, on the one surface 2a of the one glass substrate 2, the right and left micro-channels 1a are communicated with the center portion, and a plurality of nano-channels (an expansion nanoflow path or a nanoscale fine flow path 1(1b)) which has a depth of a few dozen to a few hundred nm and linearly extends in a right and left direction is formed.
(14) In addition, on one surface 6a of the other glass substrate 6, aminopropyl triethoxy silane (APTES: a silane coupling agent) 10 as a capture body (a modification object) is modified into the shape of a stripe and is disposed in a plurality of portions of the center portion. For example, a plurality of stripe-like APTES 10 having a width of 50 m (10a), 100 m (10b), 200 m (10c), and 300 m (10d) is arranged in parallel at predetermined intervals.
(15) The functional device B of this embodiment is formed by bonding the one surfaces 2a and 6a of the one glass substrate 2 and the other glass substrate 6, and by including the micro-channel 1a and the nano-channel 1b communicated with each other in an inner portion. In addition, at this time, in the functional device B of this embodiment, on one inner surface of four inner surfaces of the nano-channel 1b which is formed in the center portion to have a rectangular cross-sectional surface, each of the plurality of APTES 10 is partially modified in a predetermined position at predetermined intervals. Further, each of the micro-channels 1a in both the right and left side portions is formed by opening an end portion to the outside.
(16) Then, in the functional device B of this embodiment having the configuration described above, as illustrated in
(17) Here, according to the functional device B of this embodiment, as described above, it is possible to capture a protein in a cell within the nano-channel 1b by using the DNA 11, and thus it is possible to analyze a protein or the like expressed in a cancer cell at one cell level.
(18) In addition, when the functional device B of this embodiment, for example, injects the sample solution S including biological molecules (the target substance 11), and patterns the biological molecules 11 onto the inner surface of the nano-channel 1b of a few dozen to a few hundred nm, it is possible to perform condensation or separation, quantitative analysis, or the like with respect to the analysis sample by using an interaction between the biological molecules 11. Further, by using an extremely small space volume of the nano-channel 1b of femto liter to atto liter, it is possible to perform analysis at a single molecule level, and for example, by integrating immune assay to the nano-channel 1b, it is possible to develop a trace amount of a sample such as a single cell into a highly sensitive quantitative analysis method. In addition, when such a space is used, the size of the space is controlled and a specific surface area is extremely high, and thus it is possible to perform a highly efficient separating manipulation by using chromatography.
(19) Next, a manufacturing method of the functional device B of this embodiment will be described. When the functional device B of this embodiment is manufactured, as illustrated in
(20) In addition, as illustrated in
(21) Accordingly, the APTES 10 remains in a portion which is not irradiated with the vacuum ultraviolet light by the photomask 12, and the APTES (10a, 10b, 10c, and 10d) of a plurality of stripes having a width of 50 m, 100 m, 200 m, and 300 m is modified and formed at predetermined intervals on the one surface 6a of the other glass substrate 6. That is, a pattern of the APTES 10 as the capture body is formed. In addition, in this step, a surface of a portion on which the APTES 10 is not formed is cleaned by the vacuum ultraviolet light, and thus it is possible to provide a surface suitable for the subsequent bonding process.
(22) Next, as illustrated in
(23) Furthermore, in this embodiment, any one surface 2a (6a) of the one glass substrate 2 (6) is activated, and the one surfaces 2a and 6a of both the one glass substrate 2 and the other glass substrate 6 may be activated in a state that the APTES 10 is protected by being covered with other substrates or the like.
(24) Next, as illustrated in
(25) Conditions at this time, a confirmation method of a pattern, and the like are collectively shown in Table 1. As shown in Table 1, according to a test in which the presence or absence of leakage of a sample solution is confirmed by setting a pressure of the sample solution supplied to the fine flow path 1 to 2000 kPa, it is confirmed that the functional device B of this example exhibits a sufficient pressure resistance performance without leakage even at a high pressure of 2000 kPa, and there is no practical problem in the modification object after bonding the substrates. Furthermore, when the fluorine treatment which is one aspect of this example is performed, it is confirmed that fluorine (F) exists on an interface (the bonding portion 7). In addition, the contact angle of water is not limited to 30 as described above, and when the contact angle is able to be controlled such that the contact angle is 10 to 500, a bonding strength shown in Table 1 is able to be greater than or equal to 0.5 J/m.sup.2, and as a result thereof, it is possible to drive microfluid or nanofluid without leakage, and thus this method is able to be suitably used as a bonding method of substrates forming a microscale or nanoscale fine space.
(26) TABLE-US-00001 TABLE 1 VARIOUS CONDITIONS AND EVALUATIONS IN THIS EXAMPLE SUBSTRATE 1 EVALUATIONS TEFLON BONDING (REGISTERED STRENGTH PRESENCE OR PRESSURE TRADEMARK) BONDING CONDITIONS ACCORDING ABSENCE OF RESISTANCE (POLYIETRA- CONTACT PRES- TEMPER- TO BLADE FLUORINE ATOM PERFORMANCE CONFIRMATION OF FLUOROETH- ANGLE SUBSTRATE 2 SURE ATURE TIME TEST (PHOTOELECTRIC (PRESSURE: MODIFICATION SUBSTRATE PLASMA YLENE) [mm] [] SUBSTRATE [N] [ C.] [h] [J/m.sup.2] SPECTROSCOPY) 2000 kPa) OBJECT QUARTZ 250 M, TWO OF 30 QUARTZ GLASS IN 5000 100 2 0.7 SiF BOND NO AFTER MODIFY DNA, GLASS 40 20 WHICH APTES IS OBSERVED LEAKAGE REACT DNA WITH SECONDS 10 0.5 MODIFIED IN GAS FLUORESCENCE PHASE AND IS LABELED DNA IRRADIATED WITH HAVING COMPLE- VACUUM ULTRAVIOLET MENTARY SEQUENCE, LIGHT FOR 10 TO AND CONFIRM BY 12 MINUTES, AND USING FLUORESCENT PATTERN IS FORMED MICROSCOPE QUARTZ 250 M, TWO OF 30 GLASS IN WHICH 5000 100 2 0.7 SiF BOND NO AFTER MODIFY ANTI- GLASS 40 20 APTES IS MODIFIED OBSERVED LEAKAGE BODY, REACT ANTI- SECONDS 10 0.5 IN GAS PHASE AND BODY WITH IS IRRADIATED WITH FLUORESCENCE VACUUM ULTRAVIOLET LABELED ANTIGEN, LIGHT FOR 10 TO AND CONFIRM BY 12 MINUTES, AND USING FLUORESCENT PATTERN IS FORMED MICROSCOPE
(27) In addition, in Table 1, a crack-opening method which is often used in the related art is adopted for an evaluation of the bonding strength of the substrate. Specifically, a laser blade is inserted between the bonded substrates, and the bonding strength is calculated from a length of the substrate which is peeled off. In order to identify a fluorine atom on the surface, a substrate surface which is peeled off after being bonded is measured by a photoelectric spectroscopy, and the bonding strength is confirmed from a peak strength of energy (687.1 eV) derived from an FSi bond (a bond between fluorine and silica). A contact angle of the substrate 1 is calculated by dropping water droplets onto the substrate after being subjected to a plasma treatment and a fluorine treatment, and by imaging a contact angle at a water/glass interface on the substrate surface by using a camera. DNA or an antibody (a protein) reacting with the APTES modified on the bonded substrate flows through modification object, and is modified on a portion on which the APTES exists. In order to confirm a modification pattern of the DNA, fluorescence labeled DNA having a complementary sequence to the modified DNA flows through the modified DNA, and thus it is confirmed that the fluorescence labeled DNA is fixed to a patterning portion due to hybridization by using a fluorescent microscope. A fluorescence labeled antigen flows through the antibody (the protein), and it is confirmed that the antibody is immobilized in the patterning portion due to an antigen and antibody reaction by using a fluorescent microscope.
(28) In addition, as illustrated in
(29) That is, as illustrated in test results of
(30) Here, the fluorine concentration of the bonding portion 7 of the substrates 2 and 6 after being bonded indicates a value obtained by peeling off the substrates 2 and 6 after being bonded and by measuring the fluorine concentration of the surface.
(31) Furthermore, in this embodiment, the glass substrates 2 and 6 are bonded by being heated at approximately 25 C. to 100 C., and by being maintained at a pressure of 1000 N to 5000 N for a few hours, but the glass substrates 2 and 6 may be bonded at a temperature at which the capture body 10 (3) (an electrode 4, and a catalyst 5), and the like are not thermally damaged, and it is not necessary that a heating temperature, a pressure, a time are not particularly limited to this embodiment. A temperature at which thermal damage occurs depends on a material, and for example, when a photocatalyst such as titanium oxide is used, a structure having a high catalytic function is maintained at a temperature less than or equal to 550 C.
(32) Then, as described above, by bonding the one surfaces 2a and 6a of the pair of glass substrates 2 and 6, the functional device B is able to be formed in which the fine flow path 1 of the micro-channel 1a and the nano-channel 1b which are communicated with each other is included in the inner portion, and the APTES 10 as the capture body is partially modified and arranged in a desired position on the inner surface of the nano-channel 1b.
(33) Therefore, in the functional device B of this embodiment and the manufacturing method of the functional device B, the microscale or nanoscale fine flow path 1 is formed, and the one surfaces 2a and 6a of the one glass substrate 2 and the other glass substrate 6 on which the capture body 10 is modified and arranged are bonded while maintaining a temperature at which the capture body 10 is not thermally damaged, and thus the functional device B is formed. For this reason, as in the related art, the capture body is not thermally damaged, and the capture body 10 is able to be partially, comparatively easily, and accurately patterned in an arbitrary portion on one inner surface forming the fine flow path 1. Accordingly, it is possible to obtain the high functional device B having high accuracy and high reliability.
(34) In addition, each of the one substrate 2 and the other substrate 6 is a glass substrate, and thus it is possible to bond the one surfaces 2a and 6a at a low temperature of approximately 25 C. to 100 C. by using an activation treatment due to oxygen plasma, a hydrophilic treatment due to fluorine supplied thereto, and the like, and it is possible to form the functional device B by preventing thermal damage of the reliably capture body 10. In addition, the evaluation of the hydrophilic properties is performed by measuring the contact angle of water, and thus when the hydrophilic properties is controlled such that the contact angle of water on the substrate is 10 to 50, it is possible to solidly and preferably bond the one surfaces 2a and 6a of the substrates 2 and 6.
(35) Further, when the APTES 10 is modified on the one surface 6a of the other glass substrate 6, an unnecessary portion of the APTES 10 is decomposed and removed by being irradiated with the vacuum ultraviolet light, and the APTES 10 is used as the capture body, it is possible to perform patterning with high accuracy.
(36) In addition, by using at least one glass substrate of the substrates 2 and 6 to be bonded, it is possible to observe the inside of the flow path 1 from the outside of the functional device B by using a fluorescent microscope or the like.
(37) Further, by using a silane coupling agent as the modification object, it is possible to form a preferred capture body, and it is possible to more solidly bond the substrates 2 and 6.
(38) As described above, one embodiment of the functional device and the functional device manufacturing method of the present invention is described, but the present invention is not limited to the one embodiment described above, and is able to be suitably changed within a range not deviating from the gist thereof.
(39) For example, in this embodiment, it is described that both the one substrate 2 and the other substrate 6 are a glass substrate, but a silicon substrate may be used as any one of the substrate 2(6) or both the substrates 2 and 6. In this case, an SiO.sub.2 layer exists on a surface of the silicon substrate, and thus, similar to this embodiment, it is possible to manufacture the functional device B by bonding the one surfaces 2a and 6a of the substrates 2 and 6 at a low temperature, and it is possible to obtain the same action and effect as that of this embodiment.
(40) That is, the substrate according to the present invention may be a substrate having SiO.sub.2 on a surface, and more preferably, may be a substrate having an SiO.sub.2 layer on a surface, and by using such a substrate, it is possible to manufacture the same functional device B as that of this embodiment, and it is possible to obtain the same action and effect as that of this embodiment.
(41) In addition, in this embodiment, it is described that the APTES 10 is modified on one inner surface of the fine flow path 1 as the capture body, but the capture body (the modification object) according to the present invention is not limited to the APTES 10. For example, spermidine or the like may be used as the capture body, and may be suitably selected according to the target substance 11 to be captured.
(42) Further, in this embodiment, it is described that the capture bodies 10 and 3 are modified and arranged on one inner surface of the fine flow path 1, but the electrode 4 or the catalyst 5 (the modification object) which imparts an electrical or chemical action to the target substance 11 in the sample solution S flowing through the fine flow path 1 may be modified and arranged. Obviously, the functional device B may be configured by modifying and arranging the capture bodies 10 and 3, the electrode 4, and the catalyst 5 suitably independently or by modifying and arranging a plurality of combinations thereof.
(43) Here, as it is known, the electrode 4, for example, expresses an action causing an oxidation-reduction reaction due to electron transfer, and as an example thereof, metal such as platinum, gold, chromium, and aluminum, and the like are included. Then, when the electrode 4 is modified and arranged, a method such as a sputtering method or a chemical vapor deposition method, a physical vapor deposition method, and a plating method is able to be applied.
(44) In addition, the catalyst 5, for example, expresses an action improving a generation rate of a reactant by accelerating a chemical reaction rate, and as an example thereof, titanium oxide, palladium, iron, molybdenum, and the like are included. Then, when the catalyst 5 is modified and arranged, a method such as a sputtering method or a chemical vapor deposition method, a physical vapor deposition method, and attachment of catalyst particles is able to be applied.
(45) In addition, in this embodiment, as a method of patterning the capture body 10 (the electrode 4, and the catalyst 5) on the one surface 6a of the other substrate 6, a method is exemplified in which one surface 6a of the other glass substrate 6 having the capture body of the APTES 10 modified on the entire surface is irradiated with vacuum ultraviolet light through the photomask 12, and the APTES 10 is decomposed by being irradiated with the vacuum ultraviolet light. On the other hand, in order to pattern the capture body 10, and the electrode 4 or the catalyst 5, for example, photolithography, contact printing, an ink jet method, and the like may be used, and obviously, it is not necessary that the method is limited to a method of a decomposing manipulation using a vacuum ultraviolet method. However, after the modification, a step of cleaning an area other than the modified portion is necessary. For this reason, it is also possible to protect the modified portion with other substrates or the like and to clean the modified portion by vacuum ultraviolet light, plasma irradiation, or the like. In addition, after protecting the modified portion with the catalyst, the electrode, or the like, it may be possible to perform a chemical treatment such as acid or alkali.
INDUSTRIAL APPLICABILITY
(46) In the functional device and the functional device manufacturing method described above, the flow path is formed, and the one surfaces of the of the first substrate and the second substrate on which the modification object is modified and arranged are bonded while maintaining a temperature at which the modification object is not thermally damaged, and thus the functional device is formed. For this reason, the modification object is not thermally damaged as in the related art, and the modification object is able to be partially, comparatively easily, and accurately patterned in an arbitrary portion on one inner surface forming the flow path. Accordingly, it is possible to obtain the functional device having high accuracy and high reliability.
REFERENCE SIGNS LIST
(47) 1 Fine Flow Path 1a Micro-channel (Microflow Path, Groove) 11b Nano-channel (Nanoflow Path, Expansion Nanoflow Path, Groove) 2 One Glass Substrate (One Substrate, First Substrate) 2a One Surface 3 Capture Body (Modification Object) 4 Electrode (Modification Object) 5 Catalyst (Modification Object) 6 the Other Glass Substrate (the Other Substrate, Second Substrate) 6a One Surface 7 Bonding Portion 10 APTES (Capture Body (Modification Object)) 11 Target Substance 12 Photomask A Functional Device of the Related Art B Functional Device S Sample Solution