JP7173759B2 - microfluidic chip - Google Patents

Description

The present invention relates to a microfluidic chip produced by laminating a plurality of substrates.

A microchannel chip that integrates chemical operations such as mixing, reaction, and detection is usually produced by laminating two substrates. Since unintentional air bubbles are often trapped between the substrates during lamination, there has been a demand for further improvement in the technique for removing these air bubbles.

Patent Document 1 discloses a method for bonding a plurality of substrates. According to this method, in substrates for microchips, in which at least one substrate is provided with a channel flow path and laminated, a sub-channel communicating with the atmosphere for air discharge is separately provided on the interface side of the lamination. As a result, a minute amount of air existing between the substrates is discharged from the sub-channel to the outside, and it is possible to fabricate microchips with a high yield in which the presence of air bubbles between the substrates is hardly observed.

Patent Document 2 discloses a bonding method in which a plurality of glass substrates are superimposed and heated while applying pressure in the thickness direction of the plurality of glass substrates to bond the glass substrates. Prior to bonding, a dummy groove is formed in the bonding surface of at least one of the glass substrates separately from the flow path groove for flowing the fluid, and a through hole connected to the dummy groove and communicating with the atmosphere is formed. Disclosed is a method for bonding glass substrates characterized by: According to this method, bubbles (gas) generated on the substrate bonding surface during the pressurizing and heating processes are discharged to the outside of the substrate through the dummy grooves and the dummy through-holes, thereby preventing bubbles remaining on the substrate bonding surface. is said to be possible.

However, the above method has the following problems.
(1) There is a risk of interfacial peeling of the substrate when used in a wet environment. For example, when a microchannel chip is used in a wet environment such as an incubator, moisture enters the sub-channel that communicates with the outside air, causing interfacial peeling and increasing the risk of lowering the adhesive strength.
(2) There is a risk of leakage of liquid containing hazardous substances to the outside. For example, in the case of a microchannel chip that reacts with liquids containing harmful substances in the channels, if a secondary channel leading to the outside is provided, the liquid that is harmful to the human body will leak out of the microchannel chip through the secondary channel. There is a danger of getting out.
(3) In addition, in the case of the method of Patent Document 2, there is also the disadvantage that the production cost increases due to hole processing for forming a through hole that connects with the dummy groove and communicates with the atmosphere.
(4) Deformation of the sub-channel impairs the function of expelling air bubbles. For example, if the sub-channel is deformed and clogged during bonding of the substrates, there is a possibility that the intended discharge of air bubbles cannot be achieved.
(5) reduced functionality due to reduced usable area within the bonding interface of the substrate; In other words, if a secondary flow path for the sole purpose of removing air bubbles is provided at the bonding interface of the substrate in addition to the flow path for the main function of the product, the area that could have been used for other purposes is wasted. end up For example, if the displayable area within the bonding interface between the substrates is reduced, the amount of information that can be displayed is reduced, which hinders the addition of useful functions.

Japanese Patent Application Laid-Open No. 2003-175330 JP-A-2004-256380

SUMMARY OF THE INVENTION An object of the present invention is to provide a microchannel chip that solves the above problems.

According to the present invention, in a microchannel chip, by providing closed voids (bubble reservoirs) that are isolated from both the channel that performs the original function and the outside air, bubbles that are unintentionally sandwiched between the substrate interfaces during lamination of the substrates are provided. Provided is a microchannel chip capable of spontaneously removing trapped air bubbles.

The present invention includes the following.
[1] The first substrate and the second substrate are laminated without an adhesive,
The first substrate has rubber elasticity,
An open groove and a closed gap are provided at the interface between the first substrate and the second substrate,
the open groove is in communication with the outside air at least in one place,
A microfluidic chip having a chip body in which the closed cavity is isolated from both the outside air and the open groove.
[2] The microchannel chip according to [1], wherein the closed gap is a gap designed to receive air sandwiched between the first and second substrates when they are laminated.
[3] The microchannel chip according to [1] or [2], wherein the closed void exists in at least one of the first substrate and the second substrate.
[4] The microchannel chip according to any one of [1] to [3], wherein the closed voids further have a function of displaying information.
[5] The microchannel chip according to [4], wherein the information is character information or graphic information.
[6] The microchannel according to [4] or [5], wherein the information is at least one of product information, test liquid injection port position, test liquid injection amount, test liquid observation area, or drug information. chips.
[7] The microchannel according to any one of [1] to [3], wherein the first substrate is made of silicone rubber, which is a gas-permeable rubber film, and the second substrate is a glass substrate. chips.
[8] The microchannel chip according to [7], wherein the gas-permeable rubber is polydimethylsiloxane (PDMS).
[9] The open groove defines a test liquid introduction port, at least one drug introduction port provided with a drug holding portion, and at least one communication channel for communicating the test liquid introduction port and the drug introduction port. A microchannel having
The test liquid inlet communicates with the outside air,
The microchannel chip according to [1].
[10] The microchannel chip according to [9], wherein a drug is placed in the drug holding portion.

In general, when manufacturing a microchannel chip, bubbles are generated at the interface when two substrates are bonded together. Since a bubble pool for spontaneously absorbing air bubbles is provided, and a highly deformable material such as rubber is used for one side of the substrate, air bubbles can be spontaneously removed from the bonding interface of the substrates over time. In addition, since the air bubble pool has a structure (closed gap) that is isolated from both the flow path responsible for its original function and the outside air, even if the microfluidic chip is used in a wet environment, adverse effects such as a decrease in adhesive strength will occur. never receive

(A) is a perspective view showing a substrate of a microchannel chip according to one embodiment, and (B) is a perspective view showing a substrate of the microchannel chip to which a sealing film is attached. FIG. 2 is an enlarged plan view showing the surface of the substrate of FIG. 1, in which character information, graphic information, etc. are arranged as air bubble reservoirs (closed gaps) at places where air bubbles tend to stay. FIG. 3 is a cross-sectional view taken along the line AA in FIG. 2; FIG. 3 is a cross-sectional view taken along the line BB in FIG. 2; FIG. 5(A) is an optical microscope photograph showing how the air remaining at the bonding interface of the substrates is absorbed by the bubble pool over time, and FIG. It is a cross-sectional schematic diagram which showed a mode that it is absorbed by a bubble pool with a time change. 3 is an enlarged plan view showing one of the pairs of microchannels shown in FIG. 2; FIG. (A) to (D) are explanatory diagrams showing procedures for conducting a drug sensitivity evaluation test using a microchannel chip. FIG. 4 is a plan view showing another embodiment of the microchannel chip according to the present invention;

A microfluidic chip, also called a microfluidic device, is a general term for devices for creating microfluidic channels and reaction vessels using microfabrication technology such as MEMS technology and applying them to bioresearch and chemical engineering. In the microchannel chip according to the present invention, the first substrate and the second substrate are laminated without an adhesive, and the interface between the first substrate and the second substrate is provided with an open groove and a closed gap. There is.

In the following, the embodiment of the present invention will be described in detail with reference to the drawings, taking as an example a microfluidic chip designed to perform sensitivity evaluation of drugs to bacteria, analysis of reagents, evaluation of reactivity, etc. in a short period of time. explain.

[Configuration of microchannel chip]
A detailed description will be given below with reference to FIGS. 1 to 4. FIG.
First, the microchannel chip MF shown in FIG. 1 has a rectangular substrate 10 . The substrate 10 is formed by bonding together a first substrate 11 on the front side and a second substrate 12 on the back side.

As shown in FIGS. 1 and 3 to 4, one long side of the first substrate 11 is formed with a through-hole passing through the front surface 11a and the back surface 11b. It has a function as the liquid introduction port 13 . A through-hole is also formed in the other long side of the first substrate 11 , and this through-hole functions as a medicine introduction port 14 . Regarding the first substrate 11, the surface on which the test liquid introduction port 13 and the drug introduction port 14 are opened to the outside is defined as the surface 11a, and the bonding surface to which the second substrate 12 is adhered is defined as the back surface 11b. Surface 11 a is the surface of substrate 10 .

As shown in FIG. 4 , the portion of the second substrate 12 facing the drug introduction port 14 , that is, the bottom surface of the drug introduction port 14 constitutes a drug holding portion 15 . A portion 15 is provided.

As shown in FIGS. 2, 3, and 4, the rear surface 11b of the first substrate 11, that is, the bonding surface, is provided with a test liquid introduction port 13, and the test liquid introduction port 13 and the four drug introduction ports 14 are communicated with each other 4. A concave groove is formed for forming two communication channels 16 . When the second substrate 12 is bonded to the bonding surface of the first substrate 11, the grooves of the first substrate 11 and the second substrate 12 form a communication channel 16 at the interface between the two substrates (inside the substrate 10). be.

Thus, each test liquid introduction port 13, four drug introduction ports 14, and four communication channels 16 for communicating the test liquid introduction ports 13 with the drug introduction ports 14 form a pair of micrometers. A flow path 17 is configured.

The microchannels 17 have the same shape, extend in the width direction of the substrate 10, and are parallel to each other and provided on the substrate 10 at predetermined intervals along the longitudinal direction of the substrate 10. ing. Thus, the microchannel 17 communicates with the outside air at least through the test liquid inlet 13 (preferably also the drug inlet 14), and is referred to as an open groove in the present invention.

On the other hand, the substrate 10 is also provided with closed voids that are isolated from both the outside air and the microchannels 17 . FIG. 2 shows, as the closed gaps, 18a for displaying character information indicating the product, 18b for displaying graphic information indicating the amount of the test liquid introduced from the test liquid inlet 13, and the like. These are voids artificially designed to accept air trapped between the first and second substrates when they are laminated. Although the shape of the closed space is not particularly limited, it is preferable to use a rectangular cross section as shown in FIG.

By the way, the first substrate 11 has rubber elasticity. This is because the rubber elasticity is considered necessary to promote the later-described mechanism of moving the air trapped between the bonding interfaces of the substrates to the bubble pool (closed gap) within several seconds to several minutes. In addition, the transparency of the first substrate 11 is advantageous for observing changes in the test solution, confirming the amount of drug in the drug holding portion, checking the state of reaction between the drug and bacteria (evaluation of drug susceptibility described later), etc. preferable. It is also preferred that the first substrate 11 has gas permeability. Furthermore, it preferably has gas permeability at least equal to or higher than that of natural rubber. Although it is not desired to be bound by theory, it is expected that the air absorbed in the bubble pool (closed gap) is released into the atmosphere, and the microchannel chip is prevented from being damaged due to the expansion of the gas due to heating. Because it is done. Here, preferred materials having rubber elasticity have a tensile strength of 40-100 kg/cm ² and an elongation of 50-500% as measured according to JIS K6251:2010. Examples of rubbers having the physical properties described above include silicone rubbers, and polydimethylsiloxane is particularly recommended. Polydimethylsiloxane has a tensile strength of 70-100 kg/cm ² and an elongation of 100-500% as measured according to JIS K6251:2010, and these ranges are particularly preferred.

Moreover, the second substrate 12 may be a substrate commonly used in microchannel chips. Materials include, for example, glass, silicon, organic polymers, and glass/organic polymer composites. Glass is particularly suitable.

Note that the illustrated microchannel chip has a substrate on which a drug introduction port and a test liquid introduction port are opened and formed, and a drug holding portion and a test liquid introduction port provided on the bottom surface of the drug introduction port. A micrometer (μm)-level fine communication flow path (open groove) is formed inside the substrate for communicating with the substrate. The drug and the test liquid are brought into contact with each other by sending the test liquid introduced from the test liquid introduction port to the drug arranged in the drug holding portion through the communication channel. As a result, it is possible to perform drug sensitivity evaluation and the like by reacting the drug with the test solution. The air sandwiched between the first and second substrates when they are laminated is contained in the closed gap, and does not interfere with the bonding of the two substrates.

[Method for producing microchannel chip]
Next, a procedure for fabricating a reagent-containing microchannel chip MF will be described.

[Preparation of first substrate]
As shown in FIG. 2, a through hole forming a test liquid inlet 13 and a drug inlet 14, a concave groove forming a communication channel 16, a closed gap 18, and a closed gap 18a for displaying character information of a product. A closed space 18b or the like for displaying graphic information indicating the amount of the test liquid to be introduced is formed on the back surface 11b of the first substrate 11, and the second substrate 12 is attached to the back surface 11b to produce the substrate 10. be. In order to manufacture the first substrate 11, first, a mold provided with convex patterns corresponding to grooves constituting the communication flow paths 16 and closed gaps for displaying character information, graphic information, etc. is prepared. The liquid uncrosslinked silicone rubber, which is the raw material for , is poured into this mold and cured. (Not shown.) As a result, on the back surface 11b of the first substrate 11, there is formed a rectangular silicone rubber-made concave groove that constitutes the communication channel 16 and a closed space for displaying character information, graphic information, and the like. A substrate 11 is obtained.

Subsequently, after the substrate 11 made of silicone rubber is removed from the mold, the portion of the substrate 11 corresponding to one end side of the communication channel 16 is processed to form the test liquid introduction port 13 . Incidentally, the test liquid introduction port 13 may be formed at the same time as the substrate 11 is molded by the mold. Further, by processing the portion of the substrate corresponding to the other end side of the communication channel 16, the drug introduction port 14 is formed. The depth of the concave grooves forming the communication flow path 16 is constant as a whole.

The first substrate 11 has, for example, a long side of 40 mm, a short side of 25 mm, and a thickness of 2 mm. In addition, the depth of the groove forming the communication channel 16 is about 50 μm, the depth of the closed gap for displaying character information, graphic information, etc. is also about 50 μm, and the inner diameter of the test liquid introduction port 13 is about 1 mm. , and the inner diameter of the drug introduction port 14 is about 1.5 mm. In this way, the communication path 16 and the closed gap are collectively formed by microfabrication using a photomask.

The microchannel chip MF of the present embodiment has a form in which a plurality of pairs of microchannels 17 and a plurality of closed gaps 18, 18a, and 18b are provided on a substrate 10, but any number of microchannels 17, and a plurality of closed cavities 18, 18a, 18b may be provided in the substrate 10; Thus, the substrate 10 is provided with at least one microchannel 17 . Each microchannel 17 is composed of four drug introduction ports 14 and one test liquid introduction port 13, but the number of drug introduction ports 14 communicating with the test liquid introduction port 13 is arbitrary. can be A microchannel 17 may be provided in the substrate 10 so that one drug inlet 14 is communicated with the test liquid inlet 13 by one communication channel 16. The microchannel 17 contains at least one drug. It is sufficient if the introduction port 14 is provided.

[Preparation of second substrate]
The second substrate 12 may be a substrate that is commonly used in microchannel chips, but a glass substrate will be described below as an example. Although the closed gap is formed on the first substrate in the above description, the closed gap may be formed on the second substrate. It is sufficient that the closed gap is a gap designed to receive the air sandwiched between the first and second substrates when the first and second substrates are laminated. Existence is fine.

[Lamination of first substrate and second substrate]
By joining the second substrate 12 to the rear surface 11b of the first substrate 11 thus produced, the substrate 10 is produced as shown in FIG. 1(A).

The first substrate 11 is not particularly limited as long as it is a material having rubber elasticity, but silicone rubber is preferable, and polydimethylsiloxane is particularly preferable. When a material having rubber elasticity is used as the first substrate 11, the first substrate 11 and the second substrate 11 can be attached to each other simply by placing the first substrate 11 on the second substrate 12, without using an adhesive or the like. Twelve laminations can be made.

In addition, the first substrate 11 and the second substrate 12 are formed of a transparent material, and it is preferable that the communication channel 16 formed inside the substrate 10 be visually observed from the outside, but FIG. , the communication channel 16 is omitted from the drawing. Similarly, the sealing film 21 is also made of the same material as the first substrate 11 and is preferably transparent, but the drug introduction port 14 is omitted in FIG. 1(B).

In the present invention, the mechanism by which the air sandwiched between the first substrate and the second substrate when the first substrate and the second substrate are laminated is led to and accommodated in the closed gap will be described below.
FIG. 5(A) is a photograph showing how the air remaining at each substrate bonding interface is sucked into triangular bubble pools (closed gaps) over time. Here, the depth of the grooves forming the communication channel 16 and the depth of the closed gaps 18, 18a, 8b for displaying character information, graphic information, etc. are both 50 μm, and the inner diameter of the test liquid introduction port 13 is 1 mm. The inner diameter of the drug introduction port 14 is 1.5 mm. As shown in the uppermost photograph of FIG. 5A, immediately after the first substrate is placed on the second substrate, air 19 remains between the two substrates. However, as shown in the lower photograph of FIG. 5(A), the first substrate 11 having rubber elasticity presses the stagnant air 19, so the stagnant air 19 is led to the nearby closed gap 18 over time. He is taken into custody. This is completed within seconds to minutes after placing the first substrate on the second substrate.
FIG. 6B is a schematic cross-sectional view showing how the air 19 remaining at the bonding interface between the first substrate 11 and the second substrate 12 is absorbed by the bubble pool (closed gap) 18 over time. For easy understanding, the volume of the stagnant air 19 is exaggerated and shown large. housed in a puddle.
Further, when silicone rubber having high gas permeability is used as the first substrate, it is expected that the air once absorbed in the bubble pool (closed gap) will be released into the atmosphere. Therefore, according to the present invention, it is possible to overcome the disadvantage of the prior art that separate sub-channels and dummy through-holes communicating with the atmosphere for exhausting air must be provided.

[Introduction of chemicals]
Next, when the microchannel chip MF is used for a drug sensitivity evaluation test, the inner surface of the second substrate 12 exposed at the bottom of the drug holding portion 15, that is, the drug introduction port 14 shown in FIG. Agents are provided that are reactants against which comparative evaluations are made.

In order to dispose the drug in the predetermined drug holding portion 15, the drug is prepared by dissolving it in a solvent such as water in advance, and then the liquid drug is dripped into the inside from the drug introduction port 14 using a microsyringe or the like. be. After that, the solid medicine is fixed to the bottom portion 15 of the medicine introduction port 14 by evaporating the solvent of the medicine stored inside the medicine introduction port 14 . At this time, since most of the drug is aggregated at the bottom of the drug introduction port 14 , even if the solidified drug is peeled off from the drug holding portion 15 , the communicating channel 16 will not be closed. In particular, as shown in FIG. 6 , when an enlarged connecting portion 35 with a wide width is provided in the communication channel 16 so as to communicate with the drug introduction port 14 and directed toward the downstream side, the drug is deposited in the vicinity of the expanding connecting portion 35 . Also, the communication channel 16 is not closed.

For example, three of the four drug holding portions 15 forming the pair of microchannels 17 shown in FIG. When the drugs M having mutually different efficacy, such as different types of drugs, are fixed and the remaining one drug holding portion 15 does not hold the drug M, three types of drugs are stored in the pair of microchannels 17. Susceptibility testing for drug M can be performed. By not supplying the medicine to the remaining one medicine holding portion 15, a comparative evaluation can be made between the case where the medicine is not used and the case where the medicine is used.

Furthermore, as shown in FIG. 2, the substrate 10 is provided with six pairs of microchannels 17, so that drugs having different medicinal effects are fixed to the three drug holding portions 15 in each microchannel 17. Then, susceptibility evaluation tests for 18 kinds of drugs can be performed at the same time. If drugs with mutually different efficacy are fixed to the part 15, 23 types of sensitivity evaluation tests can be performed. Further, if drugs having mutually different efficacy are supplied to all of the drug holding portions 15 at a total of 24 locations, 24 types of sensitivity evaluation tests can be performed. Furthermore, when three types of drugs having the same efficacy were fixed to the three drug holding portions 15 of the six pairs of microchannels 17, respectively, and a sensitivity evaluation test was performed, three types of drugs against the test solution It is possible to evaluate the variation in the efficacy of the drug.

[Affixing sealing film]
As shown in FIG. 1B, a sealing film for closing the drug introduction port 14 to which the drug is supplied is provided on the surface of the substrate 10 to which the drug is supplied to the predetermined drug holding portion 15 in this manner. 21 may be attached to the first substrate surface 11a. As a result, the drug introduction port 14 in which the drug is placed in the drug holding portion 15 is closed by the sealing film 21, and as shown in FIG. is produced. Since the drug introduction port 14 is closed by the sealing film 21, even if the drug fixed to the drug holding portion 15 is separated from the drug holding portion 15, the drug is prevented from scattering outside from the drug introduction port 14. . Although the sealing film 21 is attached to the surface of the substrate 11 so as to cover all the drug introduction ports 14 constituting all the microchannels 17 shown in FIG. Alternatively, only the drug introduction port 14 may be covered. Furthermore, the entire substrate 11 including the test liquid inlet 13 may be covered with the sealing film 21 . It should be noted that the chemicals may deteriorate when exposed to moisture or oxygen in the air. When a gas-permeable material is used as the sealing film 21 , moisture and oxygen inside the drug introduction port 14 permeate the sealing film 21 , thereby allowing the drying agent placed in the package for packaging the chip body 20 . Since it is adsorbed by an agent (not shown), deterioration of the agent can be prevented.

[How to use the microfluidic chip]
[Functions of microchannel]
FIG. 6 is a plan view showing an enlarged microchannel 17 of any one of the six pairs of microchannels 17 shown in FIG. A branched portion 31 communicating with the test liquid inlet 13 is provided on the rear surface 11b of the first substrate 11, and the inner peripheral surface of the branched portion 31 has an arcuate surface having a larger diameter than the inner diameter of the test liquid inlet 13. ing. The upstream end of each communication channel 16 communicates with the test liquid introduction port 13 via a branch portion 31, and each communication channel 16 extends from the upstream side to the downstream side with an introduction portion 32 and a reaction It has a portion 33 , an observation portion 34 and an expansion connection portion 35 . The extension connecting portion 35 from the branch portion 31 is formed by a concave groove formed in the rear surface 11 b of the substrate 11 and the substrate 12 joined to the substrate 11 .

The introduction portion 32 has a tapered constriction introduction portion 32a that communicates with the branch portion 31 and has a width that narrows from the upstream end toward the downstream side, and a most constricted portion 32b that communicates with the constriction introduction portion 32a and has a substantially constant width. , and the narrowest portion 32b continues to the widened portion 32c. The widened narrowed portion 32c has a tapered shape that continuously widens toward the downstream side from the width of the narrowest portion 32b. The upstream portion of the reaction portion 33 has a constant width portion that is substantially the same as the width of the downstream end of the constricted expanded portion 32c.

The test liquid that has flowed into the introduction section 32 from the test liquid introduction port 13 passes through the constriction introduction section 32a and is sent to the most constricted section 32b. The drug is guided toward the drug introduction port 14 without remaining liquid in 32b. Further, as shown in FIG. 6, the tapering angle (reverse taper angle) of the constriction widening portion 32c is made larger than the taper angle of the constriction introduction portion 32a, so that the test liquid is directed toward the test liquid introduction port 13. backflow, that is, the occurrence of liquid return is prevented.

The downstream portion of the reaction portion 33 has a channel width narrower than that of the upstream portion of the reaction portion 33 and communicates with the narrow observation portion 34 . The four observation parts 34 that constitute one set of microchannels 17 are grouped together, and the susceptibility of the bacteria to the drug can be determined by simultaneously observing the inside of the grouped four observation parts 34 with a phase-contrast microscope or the like. Evaluate comparatively. The most downstream portion of the communication channel 16 is an enlarged connection portion 35 , and the enlarged connection portion 35 has a tapered shape in which the width continuously increases toward the drug introduction port 14 .

[Susceptibility evaluation test procedure]
When conducting a sensitivity evaluation test for the drug M, the microchannel chip MF is taken out of the package, and the sealing film 21 is peeled off from the chip body 20 .

When the microchannel chip MF is used for a drug sensitivity evaluation test, the drug is supplied in advance from the drug introduction port 14 to the bottom surface of the drug introduction port 14 , that is, the drug holding portion 15 . The test liquid is supplied from the test liquid introduction port 13 while the drug is supplied to the drug holding portion 15 . The test liquid is a culture medium containing predetermined bacteria, and is guided to the drug holding portion 15 via the communication channel 16 . When the test liquid flows through the communication channel 16, the air in the communication channel 16 is discharged to the outside through the drug introduction port 14, and the drug introduction port 14 functions as an exhaust port.

FIG. 7 is a diagram showing the procedure for conducting a sensitivity evaluation test. In FIG. and the communication channel 16 are indicated by solid lines.

FIG. 7A shows a state in which the drug M is fixed to three of the four drug holding portions 15 forming each microchannel 17 . The drug M is fixed to the drug holding portion 15 after the substrate 10 is manufactured, as described above. As shown in FIG. 7B, the test liquid L is injected from the test liquid introduction port 13 . The test liquid L is, for example, a culture medium containing predetermined bacteria, and is supplied into the communication channel 16 by a microsyringe or the like inserted into the test liquid introduction port 13 .

Next, as shown in FIG. 7(C), air is supplied to the test liquid introduction port 13 . As a result, the test liquid L that has already been introduced into the communication channel 16 from the test liquid introduction port 13 branches into four fine communication channels 16 and flows through each of the communication channels 16 to introduce the drug. It is guided to the bottom of mouth 14 . The communication channel 16 has a considerably fine portion compared to the size of the test liquid inlet 13, and the substrate 10 of the microchannel chip MF is tilted to allow the test liquid L to flow through the communication channel 16 under its own weight. Although it is difficult to make the test liquid L flow inside, the test liquid L can be reliably sent to the drug M by pushing the test liquid L into the communication channel 16 with air. In addition, in the case of a microchannel chip MF having a plurality of communication channels 16, the test liquid L is evenly branched to each communication channel 16, so in this respect also, liquid transfer by air supply is useful. is.

As shown in FIG. 7(C), when the test liquid L comes into contact with the drug M fixed to the bottom of the drug introduction port 14, the drug M dissolves in the test liquid L, and the medicinal component contained in the drug M and the test liquid L come into contact with each other. A reaction with bacteria contained in the liquid L is initiated. By maintaining this state for a predetermined time, for example, several hours, the susceptibility of the bacteria to the drug M is evaluated. Evaluation of sensitivity is performed by simultaneously observing the four channels in the observation section 34 with a phase-contrast microscope or the like.

When the test liquid L is stored in the communication channel 16 for a long time, the test liquid L is generally stored in the reaction part 33 of the communication channel 16 because the glass material constituting the second substrate 12 is highly hydrophilic. Due to capillary action, the test liquid L may flow backward over time toward the upstream side, that is, toward the test liquid inlet 13 . If the flow is reversed, the test liquids L in the plurality of communication channels 16 are mixed together via the test liquid introduction port 13, making it impossible to correctly evaluate the susceptibility of bacteria.
However, as in the microchannel chip MF of the present embodiment, the introduction portion 32 of each communication channel 16 is provided with the narrowest portion 32b, and the minimum opening area of the narrowest portion 32b is sufficient for the reaction. Since it is smaller than the portion 33, the test liquid L in the reaction portion 33 tends to wet and spread toward the test liquid introduction port 13 side. ) and the test liquid L exceeds the surface tension. As a result, as shown in FIG. 7(D), the test liquid L inside the communication channel 16 can be prevented from flowing back toward the test liquid inlet 13, so that the test liquid L is mixed as described above. can be prevented, and the susceptibility of bacteria can be correctly evaluated.

[Function to display closed voids]
As shown in FIG. 2, the primary function of the closed gap in the present invention is to accommodate air trapped between the first and second substrates when they are laminated. Furthermore, according to the present invention, it is possible to display character information, graphic information and other information in the closed space, and there is an additional advantage that the amount of information that can be displayed on the substrate can be increased. This leads to better usability of the microchannel chip, and further increases the industrial utility value of the present invention. Note that three types of closed gaps are illustrated as the closed gap 18 in FIG. That is, there are closed gaps 18 that purely function as closed gaps, closed gaps 18a that are character information indicating product information, and closed gaps 18b that are graphic information indicating the injection amount of the test liquid. Any size, number, position, and combination of closed voids can be used as long as they can accommodate bubbles generated when two substrates are laminated, such as figures, letters, or a combination thereof. Good things, of course.

[Modification]
FIG. 8(A) is a plan view showing another embodiment of the microchannel chip according to the present invention (where the logo of the product is placed where air bubbles tend to stay).

FIG. 8(B) is a plan view showing another embodiment of the microchannel chip according to the present invention (a bubble reservoir having a shape capable of removing bubbles and having other functions as well). The closed gap 18b showing the display form as graphic information of the position of the test liquid injection port, the closed gap 18b showing the display form as graphic information of the test liquid injection amount, and the observation area It has a closed space 18c, which is a display form of a combination of a plurality of graphic information to indicate.

FIG. 8(C) is a plan view showing still another embodiment of the microchannel chip according to the present invention (a bubble pool having a shape that can remove bubbles and also having other functions). A closed gap 18a showing the display form of the test liquid injection amount as character information, a closed gap 18b showing the display form of the test liquid injection amount as graphical information, and test liquid observation. It has a closed space 18b as graphic information indicating an area, and a closed space 18a indicating character information as drug information (type of drug, etc.).

The present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the gist of the present invention. Although the case of applying this microchannel chip MF to the evaluation of drug susceptibility to bacteria has been described, this microchannel chip MF can be applied to the analysis and evaluation of various objects such as reagent analysis and reactivity evaluation. can do.

10 Substrate 11 First substrate 11a Front surface 11b Back surface 12 Second substrate 13 Test liquid introduction port 14 Drug introduction port 15 Drug holding portion 16 Communication channel 17 Microchannel 18 Bubble reservoir (closed void)
18a Closed gap 18b for displaying character information Closed gap 18c for displaying graphic information Closed gap 19 displayed by combination of graphic information Air remaining at substrate bonding interface 20 Chip main body 21 Sealing film

Claims (2)

The first substrate and the second substrate are joined without an adhesive,
The first substrate is made of silicone rubber ,
At the interface between the first substrate and the second substrate , a microchannel having at least a plurality of communication channels for communicating the test liquid introduction port, the drug introduction port, and the test liquid introduction port and the drug introduction port. an open recessed groove and a closed void are provided;
the open groove communicates with the outside air at the test liquid introduction port and/or the drug introduction port when the first substrate and the second substrate are laminated ;
The closed gap is isolated from the outside air when the first substrate and the second substrate are laminated ,
It exists independently without communicating with the open groove, and
A void formed in a region where the open recessed groove is not formed in the planar portion, which is a part of the interface of the first substrate, in order to receive air sandwiched between the first substrate and the second substrate when the substrate is laminated. is
A microchannel chip having a chip body. The closed space has a function of displaying information, and the information is at least one of product information, test liquid inlet position, test liquid injection amount information, test liquid observation area information, or drug information; And,
wherein the first substrate is transparent, gas permeable polydimethylsiloxane (PDMS);
The microchannel chip according to claim 1.

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