JP2017067621A - Micro flow channel device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a technology of preventing a flow channel from being blocked by medicines fixed to the inside of an exhaust port of a micro flow channel device.SOLUTION: One end of each of four flow channels 10 disposed in a first substrate SUB 1 of a micro flow channel device is connected to each of cylindrical exhaust ports 12 to which reactants such as medicines are fixed. The outer periphery of the bottom of each of four exhaust ports 12 includes a pocket portion 13 that is connected to the exhaust port 12 and is drilled so as to extend in the radial direction of the exhaust port 12. The pocket portion 13 is formed of a recess formed in a principal surface of the first substrate SUB 1.SELECTED DRAWING: Figure 4

Description

  The present invention relates to a microchannel device, and in particular, to realize a good flow of a test solution by preventing the blockage of a channel due to fixation of a drug or the like disposed on the discharge port side of the microchannel device. It relates to effective technology.

  Development of a micro-channel device capable of executing a drug sensitivity evaluation test, reagent analysis, reactivity evaluation, etc. in a short time using a micro-meter (μm) level micro-channel is progressing.

  In Patent Literature 1, in a liquid-feeding structure including a flow path having one end connected to an open hole opened to the outside and the other end connected to a liquid absorption, the groove width of the flow path is locally changed. A technique is disclosed in which liquid feeding is performed using only capillary force without requiring a liquid feeding drive source.

  In Patent Document 2, in an analysis chip for analyzing a measurement substance in a liquid sample, a liquid sample flows from the reaction part to the discharge part by providing a blocking part between the reaction part and the discharge part of the flow path. The technique which suppresses this is disclosed. Here, the damming portion has a narrowed structure in which the channel width is narrower than the upstream side and the downstream side, or a structure in which water repellency is imparted to the inner wall of the channel.

  Patent Document 3 discloses a technique for narrowing the channel width in order to shorten the mixing time in a liquid mixing method in which at least two liquids fed through each channel are rapidly mixed at a desired mixing ratio. doing.

Japanese Patent No. 5429774 JP 2012-202925 A JP 2005-131556 A

  As an example of using a micro-channel device, after fixing a solid drug in the outlet connected to one end of the channel, introduce a test solution containing bacteria into the channel and use the drug in the outlet as the test solution. There are tests that assess the susceptibility of bacteria to drugs by dissolving them.

  The outlet of the microchannel device functions as an outlet for discharging the air that was present in the channel before the introduction of the test solution when the test solution is injected from the introduction port, and at the same time reacts with the test solution. Reaction product (medicine, etc.) is placed and fixed. In the microchannel device, the test solution and the reactant are brought into contact with each other in a minute channel and the reaction is observed. Therefore, a very small amount of the reactant is fixed to the discharge port, and excessively contacts the air. Since this should also be avoided, the opening diameter of the opening of the discharge port is about 0.5 mm to at most several mm. Therefore, it is difficult to fix the solid reactant directly in the outlet.

  Therefore, a solution in which the reactant is dissolved in a solvent such as water is prepared in advance, and this solution is dropped into the inside from the opening of the outlet using a microsyringe and the like, and then the solvent is evaporated. The method of precipitating is adopted.

  However, when a solution is dropped into the discharge port from the opening of the discharge port, a part of the solution in the discharge port may be concentrated on the opening of the flow path connected to the discharge port through the wall of the discharge port. is there. As a result, when the solvent of the solution is evaporated and the reactant is deposited in the outlet, the reactant is also deposited in the opening of the channel, the fine channel is blocked by the reactant, and before the introduction of the test solution The problem is that the air that was present in the flow path cannot be smoothly discharged, making it difficult to introduce the test solution, and the flow path is clogged with the reactant, resulting in the reactant fixed in the discharge port. Has a problem that it cannot be sufficiently dissolved in the test solution.

  An object of the present invention is to provide a technique capable of preventing blockage of a flow path caused by a reactant fixed in a discharge port connected to a flow path of a micro flow path device.

  Of the inventions disclosed in the present application, the outline of typical ones will be briefly described as follows.

  The microchannel device of the present invention has an introduction port that communicates with the outside and can inject a test solution, a discharge port that communicates with the outside and has a reactant fixed to the bottom thereof, and one end connected to the introduction port. The other end is connected to the discharge port, and the flow path for flowing the test solution supplied from the introduction port to the discharge port side is connected to the discharge port and extends in the radial direction of the discharge port. A pocket portion.

  The effects obtained by typical ones of the inventions disclosed in the present application will be briefly described as follows.

  It becomes possible to prevent the blockage of the flow channel due to the reactant fixed in the discharge port connected to the flow channel of the microchannel device.

1 is an overall perspective view of a microchannel device according to an embodiment of the present invention. It is sectional drawing along the extension direction of the flow path formed in the micro flow path device shown in FIG. It is a perspective view of the 1st board | substrate of the microchannel device shown in FIG. FIG. 4 is an enlarged perspective view of the vicinity of a discharge port of the first substrate shown in FIG. 3. It is principal part sectional drawing explaining the usage example of the microchannel device shown in FIG. (A), (b) is principal part sectional drawing explaining the usage example of the microchannel device shown in FIG. It is a principal part top view explaining the usage example of the microchannel device shown in FIG. It is a principal part top view which shows another example of the pocket part provided in the outer periphery of a discharge port. It is a principal part top view which shows another example of the pocket part provided in the outer periphery of a discharge port. It is a principal part top view which shows another example of a microchannel device.

  Hereinafter, embodiments of the present invention will be described in detail. FIG. 1 is an overall perspective view of a microchannel device according to an embodiment of the present invention, and FIG. 2 is an extension direction (first and second substrates) of the channel formed in the microchannel device shown in FIG. 3 is a perspective view of the first substrate of the microchannel device shown in FIG. 1, and FIG. 4 is an enlarged perspective view of a part (near the discharge port) of FIG. is there.

  In the microchannel device MD of the present embodiment, the first substrate SUB1 made of a transparent material having a rectangular planar shape and the second substrate SUB2 made of a transparent material having the same rectangular planar shape are bonded together. It has a structure. Here, the first substrate SUB1 is made of a silicone rubber having a siloxane bond as a main skeleton, and the second substrate SUB2 is made of a glass material or the same silicone rubber as the first substrate SUB1.

  The four first substrates SUB1 extend substantially in parallel along the long side direction of the first substrate SUB1 on a part of the bonding surface with the second substrate SUB2 (hereinafter referred to as the main surface of the first substrate SUB1). The flow path 10 is provided. As shown in FIGS. 3 and 4, these flow paths 10 are formed on the main surface of the first substrate SUB <b> 1, and are configured by concave grooves having a rectangular cross section when viewed from the long side direction of the first substrate SUB <b> 1. The cross-sectional shape of the groove forming the channel 10 is not limited to a rectangle, and may be a circle, a semicircle, or the like.

  As shown in FIG. 3, one end of each of the four flow paths 10 is connected to one introduction port 11 common to the four flow paths 10. That is, the four flow paths 10 are communicated with each other through one introduction port 11. The introduction port 11 includes a columnar through-hole that extends along the thickness direction of the first substrate SUB1 and has one end communicating with the outside of the microchannel device MD.

  On the other hand, the other end of each of the four flow paths 10 is connected to the discharge port 12. Each of these discharge ports 12 is formed of a cylindrical through-hole extending along the thickness direction of the first substrate SUB1 and having one end communicating with the outside of the microchannel device MD, like the introduction port 11.

  Each of the four outlets 12 is connected to the outlet 12 and has a pocket dug so as to extend in the radial direction of the outlet 12 (the direction from the center of the outlet 12 toward the outer circumference). A portion 13 is provided. As shown in FIGS. 3 and 4, these pocket portions 13 are constituted by recesses formed in the main surface of the first substrate SUB1.

  As shown in FIG. 4, a partition wall 14 that protrudes in the center direction of the discharge port 12 is provided between the pocket 13 and the flow path 10. Further, between the end portion of the flow channel 10 and the discharge port 12, there is an enlarged connection portion 15 that connects the flow channel 10 and the discharge port 12 and has a width wider than the width of the end portion of the flow channel 10. Is provided. Like the pocket portion 13, the enlarged connection portion 15 is configured by a recess formed on the main surface of the first substrate SUB1. In addition, although the expansion connection part 15 in this Embodiment expands in the width direction along the main surface of 1st board | substrate SUB1, it is not limited to this, It is an internal dimension in the direction in alignment with the thickness of 1st board | substrate SUB1. May be enlarged, or the inner dimension may be enlarged in both the width and thickness directions.

  In order to manufacture the first substrate SUB1 as described above, first, a mold provided with a convex pattern corresponding to the concave groove constituting the flow path 10 and the concave portion constituting the pocket portion 13 and the enlarged connection portion 15 is prepared. A liquid uncrosslinked silicone rubber, which is a raw material for the first substrate SUB1, is poured into the mold and cured. Thereby, the silicone rubber which has the rectangular planar shape in which the concave groove which comprises the flow path 10 and the recessed part which comprises the pocket part 13 and the expansion connection part 15 was formed in one surface (main surface) is obtained.

  Subsequently, after removing the silicone rubber from the mold, the inlet 11 is formed by punching out the silicone rubber at one end of the flow path 10 into a cylindrical shape. Moreover, the discharge port 12 is formed by punching out the silicone rubber at the center of the pocket portion 13 formed on the other end side of the flow path 10 into a cylindrical shape.

  As an example, the planar dimensions of the first substrate SUB1 are long side = 40 mm, short side = 15 mm, and thickness is 2 mm. Further, the depth of the concave groove constituting the flow path 10 and the depth of the concave part constituting the pocket portion 13 and the enlarged connection portion 15 (depth along the thickness direction of the first substrate SUB1) are 50 μm, respectively. 11 and the outlet 12 have a diameter of 0.75 mm. In the figure, for the sake of explanation, the outer shape of the flow path and the like is greatly expressed with respect to the size of the first substrate SUB1 and the second substrate SUB2.

  The depth of the concave portion that constitutes the pocket portion 13 may not be the same as the depth of the concave groove that constitutes the flow path 10, and is within a range in which the liquid in the discharge port 12 can flow toward the pocket portion 13 due to capillary action. Any depth is sufficient. Similarly, the depth of the concave portion constituting the enlarged connection portion 15 may not be the same as the depth of the concave groove constituting the flow channel 10.

  In addition, the pocket portion 13 may be a concave portion that gradually becomes shallower as it moves away from the discharge port 12 in order to cause a stronger capillary phenomenon, or on the side facing the connection portion of the discharge port 12 with the flow path 10. In order to cause a strong capillary phenomenon, the pocket portion 13 on the side facing the connection portion of the discharge port 12 with the flow path 10 is formed as a shallow recess in the thickness direction of the first substrate SUB1, or on the main surface of the first substrate SUB1. It is good also as a deep recessed part in the direction to follow.

  Thereafter, the main surface of the first substrate SUB1 thus manufactured and one surface of the second substrate SUB2 are overlapped and joined together to obtain the microchannel device MD of the present embodiment.

  In the example shown in FIGS. 1 and 2, the planar dimension of the second substrate SUB2 is larger than the planar dimension of the first substrate SUB1, but the planar dimension of the second substrate SUB2 is the same as the planar dimension of the first substrate SUB1. It may be.

  Further, when the second substrate SUB2 is made of silicone rubber, for example, a concave groove that constitutes the flow path 10 and a concave portion that constitutes the pocket portion 13 and the enlarged connection portion 15 are formed in the second substrate SUB2 and introduced. The microchannel device MD may be manufactured by forming through holes constituting the port 11 and the discharge port 12 in the first substrate SUB1, and then superimposing and bonding the two.

  Next, an example of use of the microchannel device MD of the present embodiment will be described. Here, the example which performs the sensitivity evaluation test of a chemical | medical agent using microchannel device MD is demonstrated.

  First, as shown in FIG. 5, a comparative evaluation is performed in a sensitivity evaluation test on the bottom of the discharge port 12 of the microchannel device MD (specifically, the surface of the second substrate SUB2 exposed at the bottom of the discharge port 12). The drug 20 which is a reaction product to perform is fixed. At this time, for example, among the four outlets 12 provided in the microchannel device MD, different amounts (volumes) of the medicines 20 are fixed to the bottoms of the three outlets 12, and the remaining one outlet 12. The drug 20 is not fixed to the bottom of the plate for comparison purposes.

  In order to arrange the medicine 20 at the bottom of the discharge port 12, as shown in FIG. 6A, after preparing a medicine 21 in which the medicine 20 is dissolved in a solvent such as water in advance, the medicine using the microsyringe 22 or the like. 21 is dropped from the opening of the discharge port 12 into the inside.

  Then, as shown in FIG. 6 (b), a part of the chemical solution 21 dropped into the inside of the discharge port 12 is caused by capillary action in the internal direction of the pocket portion 13 connected to the discharge port 12 and the flow path 10. Spreads in the radial direction toward the inside.

  However, when the pocket portion 13 is provided in the outer peripheral portion of the discharge port 12, a part of the chemical solution 21 dropped into the discharge port 12 flows toward the inside of the pocket portion 13 and collects in the pocket portion 13. . This is because the chemical liquid 21, that is, the liquid is attracted to the pocket portion 13 by capillary action. Furthermore, since the liquid has the property of aggregating, most of the chemical liquid 21 gathers in the pocket portion 13 and the vicinity thereof.

  Further, since the partition wall portion 14 (see FIG. 4) is provided between the pocket portion 13 and the flow path 10, the liquid medicine 21 that has flowed into the pocket portion 13 is blocked by the partition wall portion 14. The effect that it becomes difficult to flow backward in the internal direction of the flow path 10 along the periphery of 13 is also acquired.

  Then, the solid medicine 20 is fixed to the bottom of the discharge port 12 by evaporating the solvent of the chemical solution 21 stored in the discharge port 12 as shown in FIG. At this time, as described above, since most of the chemical liquid 21 is aggregated in the pocket portion 13 and the vicinity thereof, the solidified medicine 20 does not close the flow path 10. In particular, when an enlarged connection portion 15 having a width wider than that of the flow path 10 is provided between the flow path 10 and the discharge port 12, the opening area with the discharge port 12 is widened. Even if 20 is deposited, the flow path 10 is not closed.

  When the first substrate SUB1 is made of silicone rubber and the second substrate SUB2 is made of glass as in the present embodiment, the second substrate SUB2 is more water-soluble than the first substrate SUB1. Since the wettability with respect to the liquid is good, a larger suction force can be obtained by increasing the contact area of the second substrate SUB2 in the pocket portion 13. On the other hand, in the enlarged connection part 15, aggregation of the chemical | medical solution 21 to the enlarged connection part 15 vicinity can be suppressed by taking a large contact area with 1st board | substrate SUB1. Specifically, the pocket portion 13 is preferably a shallow and wide recess along the second substrate SUB2, and the enlarged connection portion 15 is preferably a deep recess in order to suppress contact with the second substrate SUB2.

  Thereby, it is possible to reliably prevent a problem that a part of the medicine 20 deposited on the bottom of the discharge port 12 blocks the flow path 10.

  The above-described work for fixing the medicine 20 to the bottom of the discharge port 12 is performed in a part of the manufacturing process of the microchannel device MD, for example, after the first substrate SUB1 and the second substrate SUB2 are overlapped and joined. Or the user who purchased the microchannel device MD in a state where the medicine 20 is not fixed may be performed before the sensitivity evaluation test is performed.

  Next, as shown in FIG. 7, a test solution 23 is supplied from the introduction port 11 of the microchannel device MD to the inside of the four channels 10 using a microsyringe (not shown), and then the introduction port. The test liquids 23 supplied to the inside of the four flow paths 10 are separated from each other by press-fitting air into the inside of the four flow paths 10 from 11.

  In this way, the medicine 20 fixed to the bottom of the discharge port 12 is dissolved in the test solution 23, and the reaction between the medicinal component contained in the medicine 20 and the bacteria contained in the test solution 23 is started. Then, after maintaining this state for a predetermined time (for example, several hours), by simultaneously observing the four flow paths 10 in the observation region A shown in FIG. Compare and evaluate.

  As described above, according to the microchannel device MD of the present embodiment in which the pocket portion 13 is provided on the outer periphery of the bottom of the discharge port 12, when the drug 20 is fixed to the bottom of the discharge port 12, a part of the drug 20 is present. It is possible to prevent the problem of depositing on the channel 10 and blocking the channel 10. Thereby, it is possible to provide an easy-to-use microchannel device MD that can reliably perform a highly accurate test.

  The shape of the pocket portion 13 provided on the outer periphery of the bottom of the discharge port 12 is not limited to the shape described above, and various modifications are possible. For example, as shown in FIG. The part 13 may be provided or the partition part 14 and / or the enlarged connection part 15 may not be provided as shown in FIG.

  In the embodiment, the microchannel device MD including the four channels 10 has been described. However, the number of the channels 10 provided in the microchannel device MD is arbitrarily changed according to the purpose of the test. can do. Furthermore, as shown in FIG. 10, a plurality of test units each including the flow path 10, the introduction port 11, and the discharge port 12 may be provided on one first substrate SUB1.

  The use of the microchannel device MD is not limited to the drug sensitivity evaluation test, and can be used for various applications in the biochemical field and the medical field such as reagent analysis, reactivity evaluation, chemical substance detection and chemical synthesis. .

  The present invention can be applied to a microchannel device that performs a drug sensitivity evaluation test or the like using a microchannel on the micrometer level.

DESCRIPTION OF SYMBOLS 10 Flow path 11 Inlet port 12 Outlet port 13 Pocket part 14 Partition part 15 Expansion connection part 20 Drug | medical agent 21 Chemical solution 22 Micro syringe 23 Test liquid MD Micro flow path device SUB1 1st board | substrate SUB2 2nd board | substrate

Claims (7)

An inlet that communicates with the outside and can inject a test solution;
A discharge port that communicates with the outside and the reactant is fixed to the bottom;
One end is connected to the introduction port, the other end is connected to the discharge port, and a flow path for flowing the test solution supplied from the introduction port to the discharge port side,
A pocket connected to the outlet and extending in a radial direction of the outlet;
A microchannel device comprising: The microchannel device according to claim 1, wherein
Having a bonded structure of a first substrate and a second substrate;
The introduction port and the discharge port include a through hole that penetrates the first substrate,
The flow path consists of a concave groove formed on a bonding surface of the first substrate facing the second substrate,
The pocket portion is formed of a recess formed on a bonding surface of the first substrate facing the second substrate,
The depth of the concave portion of the pocket portion along the thickness direction of the first substrate is a depth at which the liquid in the discharge port can flow to the pocket portion side by capillary action. The microchannel device according to claim 2, wherein
The first substrate is a microchannel device made of silicone rubber. The microchannel device according to claim 1, wherein
A microchannel device further comprising a partition wall portion provided between the pocket portion and the channel. The microchannel device according to claim 1, wherein
A microchannel device comprising a plurality of the pocket portions. The microchannel device according to claim 1, wherein
A microchannel device, further comprising an enlarged connection portion provided between the other end of the channel and the discharge port and having an inner dimension larger than an inner dimension of the other end of the channel. The microchannel device according to claim 1, wherein
A plurality of the outlets connected to the flow path and the other end of the flow path;
The microchannel device, wherein the plurality of channels are communicated with each other through the introduction port.

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