JP2003043052A - Microchannel chip, microchannel system and circulation control method in microchannel chip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To make realizable high versatility and to make controllable the circulation of a liquid with a simple constitution, precisely and diversely, in a microchannel chip, a microchannel system and a circulation control method in the microchannel chip. SOLUTION: In the microchannel chip 10 provided with a very small flow channel 11 through which the liquid flows and which has a very small equivalent diameter, a low affinity part 16 whose affinity to the liquid is lower than that of the inner wall surface of the flow channel 11 is formed in a part of the inner wall surface of the flow channel 11, and the low affinity part 16 is constituted of an affinity change member whose affinity degree is changed according to temperature change.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a microchannel chip that mixes liquids using minute flow paths, a microchannel system, and a flow control method in the microchannel chip.

[0002]

2. Description of the Related Art In recent years, a microchannel chip has been attracting attention, which allows various microchemical reactions to occur while a fluid is circulated using a channel having a minute channel cross-sectional area (microchannel). Such microchannel chips include, for example:
Since the cross-sectional area of the flow path is very small, a small volume of reagents and specimens is sufficient, and the specific surface area (surface area per unit volume) of the fluid flowing through the flow path is large, resulting in high heat removal efficiency. There is a merit that the reaction can be carried out efficiently. Therefore, the microchannel chip is often used to cause a synthetic reaction for the production of a predetermined substance or a reaction between a reagent and a test object for the purpose of testing.

In the microchannel chip, if the flow control can be precisely performed in the flow channel, for example, the liquid introduced into the flow channel is applied to each reagent spotted at a plurality of predetermined positions in the flow channel. It can be stopped for a predetermined period of time, which makes it possible to surely react a plurality of liquids and reagents in a predetermined order in one minute flow path, and thus it is possible to greatly expand the usage. It will be possible.

For this reason, in the microchannel chip, it has been conventionally demanded to accurately control the flow of the liquid in the channel. In a microchannel chip, for example, it is widely practiced that a liquid is circulated by a capillary phenomenon in a minute channel.

[0005]

However, when the liquid is moved by utilizing the capillarity, the capillarity is caused by the surrounding environment (pressure, temperature), the wettability of the wall surface facing the flow path, and the contact. Angle, free energy, viscosity of liquid, density,
Surface tension, interfacial tension between the wall facing the flow path and the liquid,
Since it varies subtly due to various factors such as the channel cross-sectional area, channel width, channel depth, etc., highly accurate flow control cannot be expected only by the capillary phenomenon.

Further, although the flow is controlled by simply adjusting the voltage in the electroosmotic flow or the pressure in the pressure drive, the control delay is still caused in this case, so that the above-mentioned high-precision flow control is difficult. Is. Particularly in pressure driving, since the pressure loss increases in the fine flow path, the liquid is driven at high pressure, and it is difficult to perform highly accurate flow control under such high pressure.

In addition to this, it is conceivable to control the flow by providing a microvalve in the flow passage for opening and closing the flow passage by minutely displacing the piezo element or the elastic body (for example, a polymer such as an elastomer). However, the microvalve is expensive because it requires a high level design because it is minute, and it takes time to manufacture, and the work of attaching it to the microchannel becomes a delicate work, and a more complicated control mechanism is required. Will be needed.

In addition to this, as a technique relating to flow control of a microchannel chip, for example, Japanese Patent Laid-Open No. 57-1560.
28 (Gazette 1), JP-A-6-94222 (Gazette 2), and JP-A-7-56492 (Gazette 3).
There is a technology disclosed in. Publication 1 discloses a reactor in which the movement of a fluid in a channel due to a capillary phenomenon can be controlled by setting the channel shape and various dimensions in detail.

[0009] The publication 2 discloses a microchannel chip (reaction chip) having a ventilation hole in the middle portion of the minute passage. In this reaction chip, the inside of the minute passage is opened by opening and closing the ventilation hole in the middle portion. It is possible to control the movement / stop of the liquid. Also, this reaction chip
As one of the aspects, the blood test is cited, and the shape of the flow channel and the hydrophilicity / hydrophobicity of the substrate material forming the flow channel are set so that when the blood circulating in the flow channel starts coagulation, the flow is stopped. It is set. As the substrate material, a plastic having a large surface free energy and a low water absorption rate is used. Since the plastic is hydrophobic, it is hydrophilized by argon plasma treatment and adjusted to a predetermined hydrophilicity / hydrophobicity. .

In Publication 3, a receiving chamber, a flow stop joint formed at the inlet of the receiving chamber, a sample measuring chamber and a diluent application site connected to the receiving chamber via the flow stop joint, respectively. A diluting device configured to include the above is disclosed. The stop joint can temporarily stop the sample from the sample measurement chamber before it flows into the receiving chamber. For example, the wall surface of the flow path forming the stop joint is made hydrophilic to make the receiving chamber hydrophobic. Hydrophilicity by forming with a hydrophilic material
This difference in hydrophobicity can form this termination junction. With such a configuration, the sample injected into the sample measuring chamber is once filled into the predetermined volume between the sample measuring chamber and the stop joint before the inflow of the receiving chamber, and the sample is automatically weighed. Will be done.

However, since the techniques disclosed in the above-mentioned Publications 1 and 2 are designed to control the flow of the fluid by the shape of the flow passage, the flow passage shape is designed each time according to the kind of the fluid. However, there is a problem of low versatility. Further, the technique disclosed in the above-mentioned publication 3 simply mixes the sample in the sample measurement chamber and the diluent in the diluent application site, for example, while mixing a plurality of reagents while circulating a certain liquid, It is difficult to construct a complicated system that secures a predetermined reaction time between the liquid and each reagent.

The present invention was devised in view of the above problems, and it is possible to realize high versatility, and further, it is possible to precisely and variously control the flow of a liquid with a simple structure. , And a flow control method for a micro channel system and a micro channel chip.

[0013]

Therefore, the flow-type micromixing of the present invention (Claim 1) provides a microchannel chip having a microchannel having a cross section of a microscopic equivalent diameter through which liquid flows. Than the inner wall surface that forms the flow path
A low affinity portion having a low affinity for the liquid is provided on a part of the inner wall surface of the flow channel, and the low affinity portion changes the degree of the affinity according to a temperature change. It is characterized by being constituted by.

A microchannel system according to the present invention (claim 2) comprises the microchannel chip according to claim 1 and liquid transport means for transporting the liquid in the microchannel chip. It is characterized by In this case, the liquid transporting means may be constituted by pressure driving means for driving by pressure (Claim 3), and the affinity changing member and temperature controlling means for controlling the temperature of the affinity changing member. May be provided (claim 4), or a pair of electrodes mounted in the flow path and voltage control means for controlling the voltage between the electrodes may be provided (claim 4). 5).

In the microchannel system of the present invention (claim 6), a microchannel chip having a microchannel having a cross section of a microscopic equivalent diameter through which the liquid flows, and the liquid are transported in the channel. In a microchannel system configured with a liquid transport means, a low affinity portion having a lower affinity for the liquid than an inner wall surface forming the microchannel is provided in a part of the inner wall surface, It is characterized in that the liquid transporting means is composed of a pair of electrodes mounted in the flow path and a voltage control means for controlling a voltage between the electrodes.

A method of controlling flow in a microchannel chip according to the present invention (claim 7) is the microchannel system according to any one of claims 2 to 6, wherein the step of introducing the liquid into the microchannel and the step of introducing into the microchannel. And the step of restarting the transport of the liquid in the flow path after stopping the flow of the liquid in the minute flow path in the provided low affinity portion. .

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the drawings. The term "microchannel chip" as used herein refers to a chip having a minute flow path for circulating a liquid, and in each of the following embodiments, the microchannel chip of the present invention, and thus the microchannel system and the flow control method, are particularly inspection chips. However, the application is not limited to inspection, but is used for various purposes such as synthesis reaction.

The minute channel means a channel having a channel cross section of a minute equivalent diameter such that the liquid moves in the channel by a capillary phenomenon. In addition, the liquid here includes a dispersion system such as a suspension or colloid. In addition, the hydrophobic portion referred to below means a portion having a lower affinity for the liquid flowing through the fine flow passage than the solid phase wall surface (inner wall surface) forming the fine flow passage, and the affinity is constantly solid phase. Not only those having a lower affinity than the wall surface, but also those having an affinity lower than that of the solid phase wall surface depending on the temperature are included. In addition, below, the liquid that circulates in the minute channel will be described as a water-soluble liquid.

First, a microchannel chip and a microchannel system as a first embodiment of the present invention will be described. 1 to 6 are views showing a microchannel chip and a microchannel system of this embodiment. The micro channel system as the first embodiment of the present invention is configured as an inspection device. The test device referred to here is for performing a biochemical reaction such as an antigen-antibody reaction, a protein-protein bond, a protein-low molecule bond, etc. in order to perform a predetermined test on a sample liquid. , For performing a predetermined test based on the reaction state of the sample liquid and the reagent.

Specifically, the inspection apparatus of this embodiment has an inspection chip (microchannel chip) as shown in FIG.
10 and a circulation means for circulating the sample liquid F _S injected into the minute channel 11 of the inspection chip 10. The flow means is a voltage control means (not shown) for adjusting the voltage between the pair of electrodes (electric drive parts) E1 and E2 provided on the upstream side of the hydrophobic part 16 (which will be described later) and these electrodes E1 and E2. and is configured to include bets, by applying a predetermined voltage between the electrodes E1, E2, relative to the sample liquid F _S by generating an electro-osmotic flow the sample liquid F _S to be moved in microfluidic channel You can do it.

[0021] Now, test chip 10, as shown in FIG. 1 has the fine flow path 11 for circulating the sample fluid F _S, in the fine flow path 11, the sample liquid F _S
Inlet 12 for injecting liquid into microchannel 11, reagent holder 13 on which reagent C is spotted / held, and detection for performing, for example, optical detection on a mixed liquid of sample liquid and reagent The part 14 is provided in this order from the upstream side. Further, an enlarged portion 15 is formed as a waste liquid portion at the downstream end of the introduction channel 11.

A vent hole 15a is provided in the enlarged portion 15 so that the liquid can move in the minute channel 11, and a vent hole (not shown) is similarly provided at the upstream end of the minute channel 11. . The minute flow path here means a flow path having a cross-sectional area such that liquid can be reliably transported in each flow path by a capillary phenomenon, and the equivalent diameter of the flow path cross section (= 4 x flow path cross-sectional area). / Circumferential section perimeter) is preferably in the range of 0.01 mm to 2 mm, and more preferably in the range of 0.05 mm to 1 mm.

Here, the minute channel 11 has a substrate 20 provided with a groove 20a having a predetermined shape, as shown in FIG. 2 (a).
On the other hand, by attaching the lid 21 to the side where the groove 20a is provided, a closed space having a rectangular cross section formed between the substrate 20 and the lid 21 is formed. Alternatively, FIG. 2 (b)
The thin film 22 having a through hole 22a of a predetermined shape is attached to the substrate 20 as shown in FIG.
The closed space formed between the substrate 20, the lid 21 and the thin film 22 may be formed as the minute channel 11 by further attaching the lid 21 to the side not in contact with 0.
In any case, the minute flow path 11 is formed by the inner wall surface (solid-phase wall surface) 11A made of the substrate 20 and the lid 21 (further, the thin film material 22 in the configuration shown in FIG. 2B).

As a major feature of the present invention, FIG.
As shown in, a hydrophobic part (low affinity part) 16 is provided on the upstream side of the reagent holding part 13 and on the downstream side of the injection port 12. Here, each hydrophobic portion 16 is formed over the entire circumference of the solid-phase wall surface 11A so as to surround the flow passage cross section of the minute flow passage 11. The term “hydrophobic” as used herein means that the affinity (here, hydrophilicity) for the sample liquid F _S is lower than that of the solid phase wall surface 11A formed of the substrate 20 or the like. That is, it means a relative property determined based on the affinity of the solid-phase wall surface 11A for the sample liquid F _S.

By providing the hydrophobic portion 16 in this way, the sample liquid F _S injected from the left side of the figure in FIG. 3A is moved to the right side of the figure by the capillary phenomenon as shown in FIG. 3B. When the liquid F _A moves and eventually reaches the hydrophobic portion 16 as shown in FIG. 3C, the liquid F _A tries to stay on the solid-phase wall surface 11 A having a higher hydrophilicity than the hydrophobic portion 16 and is on the upstream side of the hydrophobic portion 16. It is supposed to stop. Then, from this state, by electrically driving the electrodes E1 and E2 (see FIG. 1), the sample liquid F _S becomes hydrophobic against the flow suppressing force by the hydrophobic portion 16 as shown in FIG. 3D. It is designed to get over part 16.

The flow suppressing force required to stop the sample liquid F _S against such a capillary phenomenon is determined mainly by the hydrophobicity (affinity) of the hydrophobic portion 16 with respect to the sample fluid F _S. Then, as the material of the hydrophobic portion 16, it is preferable to use a material having a contact angle of 70 degrees or more with respect to the sample fluid F _S as described in the second embodiment described later.

More specifically, the flow suppressing force of the hydrophobic portion 16 is determined by the contact angle, the equivalent diameter D of the minute channel 11, and the circumferential length at which the hydrophobic portion 16 is provided with respect to the peripheral length of the channel cross section. Ratio (hydrophobic part length ratio, low affinity part length ratio) α [here, since the hydrophobic part 16 is provided over the entire circumference of the channel cross section, α = 1, for example, in the example shown in FIG. 4, α = L ₁ / (2
L ₂ + 2L ₃ )]. Therefore, the material of the hydrophobic portion 16 and the hydrophobic portion length ratio α may be set to satisfy, for example, the following conditions 1 to 3 in order to stop the sample liquid F _S flowing through the microchannel 11 by the capillary phenomenon. preferable.

(Condition 1) When the equivalent diameter D of the minute channel 11 is 0.2 mm to 2 mm, the hydrophobic portion length ratio α
Is set to 0.2 or more and the material of the hydrophobic portion 16 has a higher hydrophobicity than the solid-phase wall surface 11A, and a material having a contact angle θ with the sample liquid F _S of 70 degrees or more is hydrophobic. It is preferably used for the part 16. (Condition 2) Further, the equivalent diameter D of the minute channel 11 is 0.02.
In the case of mm to 0.2 mm, it is assumed that the hydrophobic portion length ratio α is set to 0.25 or more and that the hydrophobic portion 16 is made of a material having a higher hydrophobicity than the solid-phase wall surface 11A. It is preferable to use a material having a contact angle θ with the liquid F _S of 70 degrees or more for the hydrophobic portion 16.

(Condition 3) Further, when the equivalent diameter D of the minute channel 11 is 0.01 mm to 0.02 mm,
Assuming that the hydrophobic portion length ratio α is set to 0.4 or more and that the hydrophobic portion 16 has a higher hydrophobicity than the solid-phase wall surface 11A, the contact angle θ with the sample liquid F _S.
It is preferable to use a material having an angle of 70 degrees or more as the hydrophobic portion.

When the type of the liquid used as the sample liquid F _S is not specified, the contact angle θ is 70 degrees with respect to any of the liquids expected to be used in order to satisfy the above conditions 1 to 3. It is preferable to use the above materials as the hydrophobic portion 16. In addition to this, assuming that the hydrophobicity is higher than that of the minute channel 11, the contact angle θ with water of 80 degrees or more is a great guide for the material that can be used as the material of the hydrophobic portion 16, and the contact angle is 80 degrees. Examples of the above materials are polymethylmethacrylate, polycarbonate, polyvinyl chloride, wax and the like. It is more preferable to use a material having a contact angle θ with water of 90 degrees or more for the hydrophobic portion 16.

In the present invention, the contact angle .theta. Means an ambient temperature of 21.2 to 23.7.degree. C. and an ambient humidity of 30 to 38%, using a device of model number CA-A manufactured by Kyowa Interface Science Co., Ltd. The value measured under the conditions of. Now, solid phase wall surface 11A
The material for the solid phase wall surface 11A, that is, the substrate 20 and the lid 21 (the thin film material 22 in the configuration shown in FIG. 2B) are resin, ceramics, glass, The type of metal or the like is not particularly limited, but it is necessary to grasp such an affinity property because it needs to have a higher affinity for the sample liquid F _S than the hydrophobic part 16.

As a typical method for forming the minute flow path 11, as described above, the substrate 20 as shown in FIG.
A method of forming a groove 20a in the thin film 2 and a thin film-like material 2 in which a through hole 22a having a predetermined shape is formed as shown in FIG.
2 is attached to the substrate 20 to form it. In addition, the chip substrate (hereinafter,
There is also a method of integrally forming with the substrate 20).

As the method of forming the groove 20a in the substrate 20, for example, a transfer technique typified by machining, injection molding or compression molding, dry etching (RIE, IE, IB).
E, plasma etching, laser etching, laser ablation, blasting, electrical discharge machining, LIG
A, Electron beam etching, FAB), Wet etching (chemical erosion), etc. etching of channels or grooves, integrated molding such as stereolithography and ceramics filling, layering various substances, vapor deposition, sputtering, deposition part To form a fine structure by mechanically removing Sur
face Micro-machining and the like.

When the thin film 22 is attached to the substrate 20 to form a flow path, the thin film 22 can be attached by adhesive, resin joining by primer, diffusion joining, anodic joining, Eutectic bonding, heat fusion, ultrasonic bonding, laser melting, bonding with solvent / solvent,
Adhesive tape, adhesive tape, pressure bonding, bonding by self-adsorbent, physical holding, and combination by unevenness can be mentioned.

The method of forming the hydrophobic portion 16 will be described.
(Substrate 20 etc.) is partially made hydrophobic (low affinity), and conversely to this, the solid phase wall surface 11A (substrate 20 etc.) except for the predetermined part (hydrophobic part 16) is made hydrophilic ( (Higher affinity)
There is a way to do it. Acrylic resin,
Polycarbonate, polystyrene, silicone, polyurethane, polyolefin, polytetrafluoroethylene,
When using a hydrophobic material such as polypropylene, polyethylene, or thermoplastic elastomer, the method of hydrophilizing it is surface coating, wet chemical modification, gas modification, surfactant treatment, corona discharge, surface roughening, Examples thereof include vapor deposition of metal, sputtering of metal, ultraviolet treatment, and methods involving application of hydrophilic functional groups or hydrophilic molecules to the surface depending on the processing atmosphere (plasma method, ion implantation method, laser treatment, etc.).

On the solid wall surface 11A, glass, metal,
When a hydrophilic material such as ceramics is used, as a method for partially making it hydrophobic, an adhesive, a surface coating of a hydrophobic substance such as wax, a surface grafting method, a hydrophobic functional group depending on a processing atmosphere, or Examples thereof include methods (plasma method, ion implantation method, laser treatment, etc.) that involve applying hydrophobic molecules to the surface.

When the solid phase wall surface 11A is thus modified (hydrophilized or hydrophobized), the modified portion may be directly treated, or the non-modified portion may be covered with a mask or the like. The opening may be treated. That is, as shown in FIG.
As shown in (b), the channel 30 is formed from a hydrophilic solid-phase wall surface, and a hydrophobic portion is formed only on the predetermined portions 31 and 32 of the solid-phase wall surface by using the above-described modification method, or The flow path 30 is formed of a hydrophobic solid-phase wall surface, and the hydrophobic portion 31, 32 is relatively formed only on the solid-phase wall surface except for the predetermined portions 31, 32 by directly using the hydrophilic method. You may do it.

Further, as shown in FIGS. 6A, 6B, and 6C, the flow path 30 is formed of a hydrophilic solid-phase wall surface, and openings 33, 34 are formed at predetermined positions on the solid-phase wall surface. After attaching the mask 35 having
4, it is possible to form only the predetermined portions 31 and 32 as the hydrophobic portion. Alternatively, after masking only the predetermined places 31 and 32, by using the above-described hydrophilic method for the entire solid-phase wall surface, the predetermined places 31 and 3 can be obtained.
Hydrophobicizing parts other than 2 to relatively hydrophobic parts 31, 32
May be formed.

It is also possible to form a partial pattern by assembling different kinds of hydrophilic and hydrophobic materials. That is, for example, a hydrophobic material may be attached to the hydrophilic solid-phase wall surface 11A to form the hydrophobic portion. Since the microchannel chip and the microchannel system as the first embodiment of the present invention are configured as described above, the liquid flow control can be performed by the following method (the liquid flow control method as the first embodiment of the present invention). Done. The description will be given below with reference to FIGS. 1 and 3.

First, the sample liquid F _S is injected into the minute flow path 11 from the injection port 12 with a dropper, for example. The sample liquid F _S injected into the minute channel 12 moves to the right side in FIGS. 1 and 3 by the capillary phenomenon and stops at the hydrophobic portion 16. Then, after the sample liquid Fs is stopped at the hydrophobic portion 16, when the electrodes E1 and E2 are applied with a voltage, the sample liquid F _S is driven, and the sample liquid F _S gets over the hydrophobic portion 16 and flows into the reagent holding portion 13. Then, it is mixed with the reagent spotted on the reagent holding unit 13. Then, the sample liquid F _S is subjected to predetermined detection / analysis when passing through the detection unit 14, and then collected in the waste liquid unit (enlargement unit) 15.

Therefore, the sample liquid Fs can be stopped reliably and accurately at a predetermined position (upstream side of the hydrophobic portion 16), so that the sample liquid F by the electrodes E1 and E2 can be stopped.
The driving of s can be started from this predetermined position, and the sample liquid Fs can be passed through the detection unit 14 at a predetermined timing.

Further, there is an advantage that such an effect can be obtained by a simple structure in which the minute channel 11 is provided with the hydrophobic portion 16. Further, since the structure is simple, the manufacturing can be easily performed, so that there is an advantage that mass production can be easily performed and high versatility can be realized. Further, since the liquid is circulated in the minute flow path by being electrically driven by the electrodes E1 and E2 to generate an electroosmotic flow in the liquid,
There is an advantage that the position of the liquid in the minute channel can be precisely controlled with an extremely simple structure.

That is, when the liquid is driven by pressure driving for the above-mentioned circulation, pressurization is required to overcome the pressure loss of the liquid in the flow path, but the pressure loss is considered in the electric driving. You don't have to. Further, the voltage switching enables precise fluid handling. further,
Since a mechanical pump drive mechanism is unnecessary, the configuration of the entire device can be simplified.

Next, a micro channel chip and a micro channel system as a second embodiment of the present invention will be described. 7 to 9 are views showing the microchannel chip and the microchannel system of the present embodiment. The components already described in the above-described first embodiment are designated by the same reference numerals, and the description thereof will be omitted.

The inspection apparatus (microchannel system) of the present embodiment is configured substantially the same as the inspection apparatus of the first embodiment, and as shown in FIGS. 7 and 8 (a), an inspection chip (microchannel chip). 10A and inspection chip 10
And a circulation means for circulating the sample liquid F _S in the microchannel 11 of A. The circulation means is a pair of electrodes (electric drive section) provided on the upstream side of the hydrophobic section 16. E1 and E2 and voltage control means (not shown) for adjusting the voltage between these electrodes E1 and E2 are provided.

The inspection chip 10A has a structure in which a hydrophobic portion (low affinity portion) 16 is provided on the upstream side of the injection port 12 with respect to the inspection chip 10 of the first embodiment (others are the inspection chip 10 and the inspection chip 10). The explanation is omitted because it is similar). The microchannel chip and the microchannel system according to the second embodiment of the present invention are configured as described above, and FIG.
As shown in FIG. 8A, the injection port 12 is surrounded by the hydrophobic portions 16 and 16, and as shown in FIG.
When it is dripped toward, the sample liquid F _S is injected into the injection port 12
The microscopic flow path 11 is further invaded and the inside of the micro flow path 11 is shown in FIG.
As shown in (c), it progresses in the left-right direction in the figure due to the capillary phenomenon, but as shown in FIG. 8 (d), it stops at the hydrophobic portions 16, 16.

Therefore, for example, even if the sample liquid F _S is excessively dropped in FIG. 8B,
The sample liquid F _S does not enter a predetermined amount or more due to the flow regulation by the hydrophobic parts 16, 16. That is, there is an advantage that the sample liquid F _S is automatically weighed between the hydrophobic parts 16, 16. Then, from the state shown in FIG. 8D, the electrodes E1 and E2 [see FIG. 7 and FIGS.
(E) (not shown) is applied with a predetermined voltage.
By driving the right direction _S in FIG. 8 (a) ~ FIG 8 (e), the sample liquid F _S overcame hydrophobic portion 16, the reagent holding section 13, and an inspection portion 14 flows into the drainage member 15 Be recovered.

The sample liquid F _S in the minute channel 11
As shown in FIG. 9, a fluid which is insoluble in the sample liquid F _S around the electrodes E1 and E2 in the minute channel 11 (the liquid may be a gas, as a matter of course) so as not to adversely affect F _X may be filled and the sample liquid F _S may be driven via this fluid F _X. Next, the third aspect of the present invention
A microchannel chip and a microchannel system as an embodiment will be described. 10 and 11
FIG. 3 is a diagram showing a microchannel chip and a microchannel system of the present embodiment. In addition, the description of FIG. 8 used in the second embodiment will also be applied. The components already described in each of the above-described embodiments are designated by the same reference numerals, and the description thereof will be omitted.

The inspection chip (microchannel chip) 10B of the present embodiment is configured by providing an injection port 12, a reagent holding portion 13, a detection portion 14 and a waste liquid portion (enlargement portion) 15 in the microchannel 11 from the upstream side. ing. And the detection unit 1
4, the hydrophobic portions 16 and 16 are provided on the upstream side and the downstream side of the inlet 12. Further, a ventilation port 11 a is provided at the upstream end of the micro flow channel 11 so that the sample fluid F _S can move in the micro flow channel 11, and the waste liquid portion 1
A ventilation port 15 a is provided at the downstream end of the No. 5.

In this case, the hydrophobic parts 16 and 16 are special.
Is composed of an affinity changing member. Affinity change part
The material is a sump that flows through the minute flow path 11 according to a temperature change.
Liquid F _SAffinity changes to, here
Then, with a polymer gel whose hydrophilicity changes with temperature changes
Using a certain temperature sensitive gel (affinity changing member),
Typical of such a temperature sensitive gel, P
IPAAm [Poly (N-isopropyl acrylic amine
D)] Gel is used.

This PIPAAm gel hydrates at low temperatures and dehydrates at high temperatures, and accordingly it becomes hydrophilic at low temperatures and hydrophobic at high temperatures. P
An aqueous solution of a linear polymer of IPAAm is LCST (Lo
wer Critical Solution Temp
It has a characteristic that it becomes hydrophilic at a temperature equal to or lower than the temperature (erature) and becomes hydrophobic at a temperature higher than LCST.

The LCST of PIPAAm is about 32 ° C., and the temperature can be easily controlled by an ordinary heating / cooling mechanism. That is, since the LCST is around the atmospheric temperature T _ATM , the temperature control width (ie, LCST-T _ATM ) required to reverse hydrophilicity / hydrophobicity is small, so that temperature control is easy to perform. Other temperature sensitive gels include DE
AAm (N, N-diethylacrylamide) gel (LC
ST = 25 to 32 ° C.), pAPP (poly-N-acryloylpiperidyl) gel (LCST≈5 ° C.), and copolymers of the above polymers. Also, p of the usage environment
It is also possible to adjust LCST according to H, copolymerization ratio, and the like.

Further, the inspection apparatus (microchannel system) of the present embodiment, in addition to the above-mentioned analysis chip 10B,
As a liquid transporting means for transporting the sample liquid F _S in the minute channel 11, a temperature control device (temperature control means) 40 for controlling the temperature of the hydrophobic portion 16 is provided. As shown in FIG. 11A, each of the temperature control devices 40 has a substrate 2
The electric heating plate (for example, a copper plate) 41 embedded in 0 and connected to the hydrophobic portion 16 respectively, the thermocouple (temperature sensor) 41a attached to the electric heating plate 41, and the hydrophobic portion 14 via the electric heating plate 41a. Peltier element 42 for heating / cooling
A heat sink (heat dissipation plate) 43 superposed on the Peltier element 42, and a control device 44.

The Peltier element 42 heats / absorbs heat in accordance with the supplied voltage, and the control device 44 controls the thermocouple 41a so that the hydrophobic portion 14 reaches a predetermined temperature input from an input means (not shown). The voltage supplied to the Peltier element 42 is feedback-controlled on the basis of the temperature information of the hydrophobic portion detected by. In the temperature control device 40, as the temperature sensor, as shown in FIG. 11B, an infrared sensor 41 is used instead of the thermocouple 41a.
b may be used. In addition, as shown in FIG.
The Peltier element 42 is mounted on the substrate 4 without the electric heating plate 41.
It may be embedded in 0 and directly connected to the hydrophobic portion 16.

Microchip as a third embodiment of the present invention
The channel chip and microchannel system are described above
Since it is configured as follows, distribution control is performed as follows.
Is performed. That is, first, if necessary, the control device 4
Controlling the temperature of the hydrophobic part 16 via 4 to make it hydrophobic
After that, as shown in FIG. 8B, the sample liquid F_STo
For example, it is dropped on the injection port 12 with a dropper or the like. Figure 8
As shown in (c), this sample liquid F_SIs inlet 1
2 penetrates into the hydrophobic part 1 as shown in FIG.
Distribution is regulated by 6, 16. That is, dropped
Sample liquid F _SOnly a predetermined amount of the
It can infiltrate.

Then, after removing the excess sample liquid F _S around the injection port 12 that could not penetrate into the minute channel 11, as shown in FIG. The temperature of the hydrophobic portion 16 is controlled via the control device 44 to reverse the hydrophobic portion 16 to be hydrophilic. As a result, the sample liquid F _S resumes its movement due to the capillary phenomenon, flows into the waste liquid portion 15 via the reagent holding portion 13 and the inspection portion 14, and is collected. Therefore, the same effect as the second embodiment can be obtained.

Further, since the inspection chip (microchannel chip) 10B has a small substrate and the like on which the inspection chip 10B is formed and has a small heat capacity, the temperature control of the heat-sensitive gel (hydrophobic part) 16 can be achieved with a relatively short response time. Sample liquid F _S
There is an advantage that distribution control of can be performed. Note that FIG.
In the inspection apparatus of the present embodiment shown in FIG. 2, the fluid driving means is pressure driving means such as a syringe pump or the electrode E.
It is also possible to provide an electric drive means such as 1, E2 or the like. If connecting a syringe pump, see FIG.
A tube 50 may be connected to the ventilation port 11a on the upstream side as indicated by a chain double-dashed line, and the syringe pump and the microchannel 11 may be connected via the tube 50.

The microchannel chip of the present invention,
The microchannel system and the distribution control method are not limited to those of the above-described embodiments, and can be variously modified without departing from the spirit of the present invention. For example, in the above-described second embodiment and third embodiment, two hydrophobic parts 16 and 16 are provided so as to sandwich the injection port 12, and liquid intrusion from the injection port 12 is restricted between these hydrophobic parts 16 and 16. By doing so, the liquid can be weighed. However, as shown in FIGS. 12A to 12E, the hydrophobic portion 16 is provided at the bottom of the minute channel so as to surround the injection port 12 in a top view. It may be configured as follows.

In this case, the sample fluid F _S dropped toward the injection port 12 as shown in FIG.
As shown in (c), it infiltrates into the minute channel 11 through the inlet 12 and falls into the region surrounded by the hydrophobic portion 16 at the bottom. Movement of the dropped sample fluid F _S in the minute channel is restricted by the hydrophobic portion 16 as shown in FIG. 12C, and finally in the hydrophobic portion 16 as shown in FIG. 12D. A predetermined amount of the sample fluid F _S is dropped onto the injection port 12, and the excessive amount of the sample fluid F _S drops in the minute channel 1.
1 cannot be penetrated and remains around the inlet 12.

Then, after removing the excess amount of the sample fluid F _S and sealing the injection port 12, the sample fluid F _S in the minute channel 11 is pressure-driven or electrically-driven, so that FIG. It is possible to get over the hydrophobic portion 16 as shown in FIG. Of course, the hydrophobic portion 16 may be made of a temperature responsive gel, and the hydrophobic portion 16 may be made hydrophilic by controlling the temperature.

Further, as shown in FIG. 13, a plurality of (here, four) hydrophobic parts 52 may be provided in the minute flow path 51 so that the position of the liquid F _A can be controlled at another stage. That is, if the pressure driven or electrical driven liquid F _A, if stopping the driving according to each of the liquid F _A gets over the hydrophobic section 52, the liquid F _A on the upstream side of the hydrophobic portions 52
Can be stopped (the liquid F _A can be stopped in multiple steps within the flow path 51). Further, if the hydrophobic part 52 is composed of a temperature sensitive gel, temperature control can be performed for each hydrophobic part 52. By doing so, it becomes possible to stop the liquid F _A on the upstream side of each hydrophobic portion 52.

Thus, for example, if different reagents are spotted on the upstream side (or the downstream side) of each hydrophobic portion 52, the liquid F _A is allowed to react with each of these reagents in a predetermined reaction time and in a predetermined manner. You will be able to mix in the order of. Alternatively, when the hydrophobic part 52 is made of a temperature responsive gel, the steps shown in FIGS. 14A to 14D can be performed. That is, as shown in FIG. 14A, the liquid F _A that moves due to the capillary phenomenon overcomes the hydrophobic portion 52 in the hydrophilic state and then is temperature-controlled (here, heated) to be reversed to the hydrophobic state. _As shown in FIG. 14 (b), _A is stopped with its tip (downstream end) over the hydrophobic portion 52, or as shown in FIG. 14 (c), the hydrophobic portion 52 in the liquid F _A Only the portion on the downstream side can be separated and moved by the capillary phenomenon. If the liquid F _{A is} to be separated in the minute flow path 51 as described above, it is necessary to provide a vent hole in the hydrophobic portion 52.

[0063] Further, when applying the example shown in FIG. 14 (c), as shown in FIG. 14 (d), the liquid F _A in the flow path 51
By disposing a plurality of hydrophobic parts 52 along the flow direction of, it is possible to separate the liquid F _A for each hydrophobic part 52. Further, as shown in FIGS. 15 (a) and 15 (b), a plurality of flow paths 51A to 51F are arranged in parallel, and
By providing the hydrophobic portions 52 at the same position in the flow direction of the liquid F _A in each of the flow paths 51A to 51F, respectively,
As shown in (a), even if the tip positions of the respective liquids F _A flowing through the respective flow paths 51A to 51F are varied, these liquids F _A are stopped by aligning the tip positions with the hydrophobic portion 52. be able to.

Thus, for example, if an optical analysis is performed on each liquid F _A , it is possible to simultaneously irradiate each liquid F _A with light only once by irradiating the range shown by the alternate long and short dash line in FIG. It becomes possible to perform an analysis. Also,
In the microchannel chip of each of the above-described embodiments, an example in which the detection unit 14 is configured as an enlarged portion with respect to the minute channel has been described, but a portion of the minute channel 11 is used as the detection unit without providing the enlarged portion. You may. Further, although the waste liquid portion is constituted by the enlarged portion 15 at the lower end of the minute channel 11, the enlarged portion 15 is not provided and the waste liquid is discharged to the outside from the discharge port provided at the downstream end of the minute channel 11. Is also good. Alternatively, the detection unit 14 is not provided, and the mixed liquid of the sample liquid F _S and the reagent is discharged to the outside from the discharge port provided at the downstream end of the minute channel 11, and the predetermined detection is performed outside the test chip. You may do it.

In the first and second embodiments, when a sufficient voltage for driving the sample liquid F _S cannot be applied with one set of electrode pairs, a plurality of sets of electrode pairs are used. Is also good.

[0066]

EXAMPLE (A) First Example A first example of the present invention will be described below with reference to FIGS. 16 (a) to 16 (c). 86 mm long x 32 mm wide, 1.0-1.2 mm thick slide glass 71 (S-11
12 、 MATSUNAMI) 10m by applying wax
Two hydrophobic parts 72, 72 having a width of m were formed along the width direction (short direction) of the slide glass 71 with an interval of 20 mm. And this slide glass 71 has a width of 15 m
m double paper double-sided tape (NW-15, Nichiban) 7
3, 73 were pasted at intervals of 2 mm along the length direction (long direction) of the slide glass 71 [Fig.
State shown in (a)].

Next, the diameter is 2 mm with a space of 35 mm.
76 mm long with 26 holes 74a, 74b
mm, 1 mm thick acrylic resin plate (Acrylite # 0
No. 01, Mitsubishi rayon) 74, and wax is applied so that one hole 74a is sandwiched, and a hydrophobic portion 75, 75 having a width of 10 mm is formed.
Were formed along the width direction (short direction) of the acrylic resin plate 74 at intervals of 20 mm [state shown in FIG. 16 (b)].

Then, the slide glass 71 and the acrylic resin plate 74 were adhered so that the hydrophobic portions 72, 72 and the hydrophobic portions 75, 75 face each other via the paper double-faced tape 73. As a result, a flow path 76 was formed between the slide glass 71, the paper double-sided tape 73, and the acrylic resin plate 74 [state shown in FIG. 16 (c)]. Next, after sealing a part of the flow path 76 with an adhesive outside the hole 74b, 10
μL of normal goat serum (Goat Serum, GIBC
(O BRL) was dropped into the hole 74b, the normal goat serum moved in the flow path 76 by a capillary flow and stopped at the hydrophobic portion 72 (75) on the right side in the figure.

Then, when an electrode (not shown) is inserted into the hole 74b and a predetermined voltage is applied to electrically drive the same, a part of the goat serum normally gets over the hydrophobic portion 72 (75) and the hydrophobic portion 72.
It moved between (75) and 72 (75). And hole 74
When an electrode (not shown) is inserted into a and is electrically driven by applying a predetermined voltage, it starts moving on the hydrophobic part 72 (75) on the left side in the figure, gets over this hydrophobic part 72 (75), and goes out of the flow path 76. Spilled. (B) Second Embodiment Hereinafter, FIGS. 17 (a) to (c) and FIGS. 18 (a) to (c).
The second embodiment of the present invention will be described with reference to FIG. (B-1) Preparation of Chip First, description will be made with reference to FIGS.
2 mm in diameter at the center of a lid 80 having a length of 60 mm and a width of 20 mm which is made of a polymethylmethacrylate plate (Acrylite # 001, Mitsubishi rayon, hereinafter referred to as PMMA)
Hole (injection port) 81 is formed, and transparent adhesive tapes 82 having a width of 15 mm are attached as masks to both ends of the lid 80 in the length direction (long direction) along the width direction (short direction). After that, a plasma irradiator (ST-
7,000, keyence), HIGH mode, In
t. The lid portion 80 was irradiated with plasma for 3 seconds by air. As a result, the central portion (hydrophilic portion) 83 of the lid portion 80 to which the transparent adhesive tapes 82, 82 are not attached is made hydrophilic.
Then, after peeling the transparent adhesive tapes 82, 82 from the lid 80, two paper double-sided tapes (NW-15, Nichiban) 84 are provided on the lid 80 along the length direction (long direction) thereof.
Were pasted with a space of 2 mm [state shown in FIG. 17 (a)].

Next, PMMA (Acrylite # 00
1, a transparent adhesive tape 92 having a width of 15 mm is attached as a mask to each end of a chip substrate 90 having a length of 60 mm and a width of 20 mm, which is made of Mitsubishi Rayon) [state shown in FIG. 17 (b)]. Then, using a plasma irradiator (ST-7000, KEYENCE) not shown, HIGH
Mode, Int. The chip substrate 90 is irradiated with plasma for 3 seconds by the air, whereby the central portion (hydrophilic portion) 93 of the chip substrate 90 to which the transparent adhesive tape 92 is not attached is attached.
Was hydrophilized.

After peeling the transparent adhesive tapes 92, 92 from the chip substrate 90, the lid 80 and the chip substrate 9 are removed.
0 via the paper double-sided tape 84
And so that they face each other, and the lid 8
0, 2 m between the chip substrate 90 and the paper double-sided tape 84
A PMMA chip 100A-2 having an m-width channel (fine channel) 85 was formed. In this case, in the flow path 85, the regions 86 and 96 other than the hydrophilic parts 83 and 93 are relatively (lower hydrophilic than the hydrophilic parts 83 and 93) hydrophobic parts.

Then, according to the above-mentioned methods, the lid 80 and the chip substrate 90 are made of polycarbonate (Stella S).
PC chip 100B-2 made of 300, thickness 1 mm, Mitsubishi resin, hereinafter referred to as PC), and lid portion 8
0, a PVC chip 100C-2 in which the chip substrate 90 is made of vinyl chloride (a vinyl chloride plate, acrysanday, hereinafter referred to as PVC) was manufactured.

In addition, according to the above procedure, the flow channel 85 has a width of 1 mm, and other configurations are substantially the same as those of the chips 100A-2 and 100B-2. Chip 100B-1 was prepared. Furthermore, a chip in which the hydrophobic portions 86 and 96 are formed by the wax was prepared by the following method.

That is, to explain with reference to FIGS. 18 (a) to 18 (c), first, a length of 60 mm × width composed of a polymethylmethacrylate plate (Acrylite # 001, Mitsubishi Rayon, hereinafter referred to as PMMA). A hole 81 having a diameter of 2 mm is formed in the center of the lid portion 80 of 20 mm.
A 15 mm-wide transparent adhesive tape (lion) 82 is attached as a mask along the width direction (short direction) at the center of the length direction (long direction). At this time, the transparent adhesive tape 8
2 was aligned such that both ends thereof were 15 mm apart from both ends of the lid 80, respectively. By applying wax in this state, both end portions (hydrophobic portions) 86, 86 of the lid portion 80 to which the transparent adhesive tape 82 is not attached are made hydrophobic.

Then, from the lid 80 to the transparent adhesive tape 82.
After peeling off, two paper double-sided tapes (NW-15, Nichiban) 84, 84 were attached to the lid 80 along the length direction (long direction) with a space of 2 mm. [State shown in FIG. 18 (a)]. Next, a transparent adhesive tape (lion) 92 having a width of 15 mm was attached as a mask to the center of a chip substrate 90 having a length of 60 mm and a width of 20 mm made of PMMA (Acrylite # 001, Mitsubishi Rayon) [Fig. The state shown in b)]. Then, by applying wax in this state, both end portions (hydrophobic portions) 96, 96 of the chip substrate 90 to which the transparent adhesive tape 92 is not attached are made hydrophobic. Then, the transparent adhesive tape 92 was peeled off from the chip substrate 90.

Then, the lid portion 80 and the chip substrate 90 are attached to each other via the paper double-sided tape 84 so that the hydrophobic portions 86 and 96 face each other, whereby the lid portion 80,
A PMMA chip 100D-2 having a flow path 85 with a width of 2 mm was formed between the chip substrate 90 and the paper double-sided tape 84. In this case, in the flow path 85, the hydrophobic portion 8
Areas 83 and 93 other than 6 and 96 are relatively (hydrophobic part 8
(More hydrophilic than 6,96).

Then, a PMMA chip 100D-1 having a channel width of 1 mm was manufactured by the above-mentioned methods. Similarly, a plasma-processed PM with a channel width of 2 mm
MA chip 100E-2 was manufactured. (B-3) Liquid stop test Next, ethanol [reagent special grade (99.5%), pure chemistry] was added to pure water and stirred, and as shown in Table 1 below, 11 kinds of ethanol solutions having a predetermined volume concentration were prepared. (Water diluted ethanol)
It was created. Then, the ethanol solution and the demineralized water are dropped into the injection port 81 of each of the chips, and the ethanol solution stands still at the boundary position of plasma irradiation or wax application position (that is, the boundary between the hydrophilic portion and the hydrophobic portion). Whether or not the temperature was 23 ° C. and the humidity was 38% was observed. After the observation, the liquid was completely removed from the flow channel with compressed air and used for the next observation.

The results are shown in Table 1 below. "○" in Table 1
Indicates that the ethanol solution or demineralized water was stationary at such a boundary position, and “X” in Table 1 indicates that the ethanol solution or deionized water was not stationary at such a boundary position. In addition, “n” in Table 1 indicates the number of measurements.

[0079]

[Table 1]

As is clear from Table 1, the hydrophilic part 8
3, 93, regardless of the material and flow path width, the hydrophobic portion 86,
If the material of 96 was the same, the stopping tendency of the liquid was the same (the concentration of the ethanol solution at which the ethanol solution stops at the hydrophobic portions 86 and 96 was the same). In other words, even if the hydrophilic parts 83 and 93 are made of the same material and the channel width is the same, if the hydrophobic parts 86 and 96 are made of different materials, the stopping tendency of the liquid is different. (B-4) Contact angle measurement From this, it is presumed that the dominant factor of the liquid stop in the fine channel is the wettability of the hydrophobic parts 86 and 96, and
The contact angle θ between each liquid and each material of the hydrophobic parts 86 and 96 was measured. Measuring device is Contact Angl
Using an e Meter (model CA-A, Kyowa Interface Science), the measurement was performed under the conditions of 23 ° C. and humidity of 38%. The results are shown in Table 2 below. In addition, “○” and “×” in Table 2 are shown in Table 1.
It corresponds to. For example, in Table 2, the combination of the hydrophobic material and the ethanol solution concentration is "PMMA".
"○" is entered in the column indicating that "11.11v / v%" and "11.11v / v%" indicate that the liquid stopped due to the combination in the liquid stop test.

[0081]

[Table 2]

FIG. 19 corresponds to Tables 1 and 2 above, in which the vertical axis is the contact angle θ and the horizontal axis is the ethanol concentration (EtOH concentration) of the ethanol solution. In addition, “◯” and “×” in the figure are the same as those in Tables 1 and 2, and “◯” indicates that the liquid has stopped at the hydrophobic portions 86 and 96 (has a liquid stop barrier function). ] Is the hydrophobic part 8
6, 96 shows that the liquid did not stop (no liquid stop barrier capability).

As can be seen from Table 2 and FIG. 19, when the contact angle θ between the liquid and the material is 70 ° or more, the liquid is the hydrophobic part 86, 9 under all conditions regardless of the material of the hydrophobic part.
It was found that the liquid stopped at 6 while the contact angle θ was less than 70 °. In other words, it was found that when the hydrophobic portions 86 and 96 have a contact angle θ of 70 ° or more with respect to the liquid flowing by the capillary force in the minute flow path, the flow of the liquid can be stopped. .

When the representative length of the flow path becomes shorter,
It is expected that the pressure difference caused by the curvature of the meniscus will be large, that is, the liquid transport capacity due to the capillary phenomenon will be large, so the stop-non-stop threshold value at the hydrophobic portion of the liquid (the moving liquid is reliably stopped by the capillary phenomenon The contact angle of the hydrophobic parts 86 and 96) is 70 ° above.
It is expected that the angle will be larger than that.

[0085]

As described in detail above, according to the present invention,
After the liquid in the microchannel stops flowing on the low-affinity portion provided in the microchannel, the transport of the liquid in the channel is restarted, so that the low-affinity portion is partially formed in the microchannel. With such a simple configuration, it is possible to precisely and diversify the flow control of the liquid, and because of the simple configuration, there is an advantage that manufacturing can be easily performed and high versatility can be realized.

[Brief description of drawings]

FIG. 1 is a schematic plan view showing a configuration of a microchannel chip and a microchannel system as a first embodiment of the present invention.

FIG. 2 is a diagram showing a configuration of a microchannel chip as the first embodiment of the present invention, (a) is a schematic cross-sectional view, and is a diagram corresponding to the XX cross section of FIG. 1; [Fig. 3] is a schematic side view showing a modified example of (a).

3A to 3D are schematic plan views for explaining the operation of the microchannel chip according to the first embodiment of the present invention.

FIG. 4 is a schematic diagram for explaining the definition of a hydrophobic portion length ratio (low affinity portion length ratio) α according to the first embodiment of the present invention, and is a schematic diagram corresponding to the YY cross section of FIG. 1. Is.

5 (a) and 5 (b) are views for explaining a method for modifying a solid-phase wall surface according to the first embodiment of the present invention, which is a plan view of relevant parts of a microchannel chip.

6 (a), (b), (c) are views for explaining a method for modifying a solid-phase wall surface according to the first embodiment of the present invention, and are plan views of a main part of a microchannel chip. is there.

FIG. 7 is a schematic plan view showing the configurations of a microchannel chip and a microchannel system as a second embodiment of the present invention.

FIGS. 8A to 8E are schematic plan views for explaining the operation of the microchannel chip according to the second embodiment of the present invention.

FIG. 9 is a schematic plan view showing a configuration of a modified example of the microchannel chip and the microchannel system as the second embodiment of the present invention.

FIG. 10 is a schematic plan view showing the configurations of a microchannel chip and a microchannel system as a third embodiment of the present invention.

11 (a), (b), and (c) are diagrams showing a configuration of a temperature control device according to a micro-channel system as a third embodiment of the present invention, taken along the line ZZ in FIG. It is a corresponding schematic diagram.

FIGS. 12A to 12E are schematic plan views showing the configuration of a main part of a microchannel chip as another embodiment of the present invention.

FIG. 13 is a schematic plan view showing a configuration of a microchannel chip as another embodiment of the present invention.

14A to 14D are views for explaining a flow control method as another embodiment of the present invention, and a schematic plan view of a microchannel chip.

15 (a) and 15 (b) are schematic plan views for explaining the configuration and action of a microchannel chip as another embodiment of the present invention.

16 (a), (b) and (c) are views for explaining the structure and manufacturing method of the microchannel chip as the first embodiment of the present invention, and are schematic plan views of the microchannel chip. It is a figure.

17 (a), (b) and (c) are views for explaining the structure and manufacturing method of the microchannel chip as the second embodiment of the present invention, and are schematic plan views of the microchannel chip. It is a figure.

18 (a), (b), and (c) are views for explaining the structure and manufacturing method of the microchannel chip as the second embodiment of the present invention, and are schematic plan views of the microchannel chip. It is a figure.

FIG. 19 is a diagram showing a correlation of the contact angle θ, the ethanol concentration, and the liquid stopping barrier ability of the hydrophobic part according to the second example of the present invention.

[Explanation of symbols]

10, 10A, 10B Inspection chip (micro channel chip) 11 Micro channel 11A Inner wall surface (solid phase wall surface) 12 Injection port 13 Reagent holding part 14 Detection part 15 Expanded part (waste liquid part) 15a Vent 16 Hydrophobic part (low affinity) 20) Substrate 20a Groove 21 Lid 22 Thin film 22a Through hole 31, 32 Predetermined location (hydrophobic part) 33, 34 Opening 35 Mask 40 Temperature control device 41 Heating plate 41a Thermocouple (temperature sensor) 41b Infrared sensor (temperature) 42) Peltier element 43 Heat sink (heat sink) 50 Tube 51 Micro flow path 52 Hydrophobic part 71 Slide glass 72 Hydrophobic part 73 Paper double-sided tape 74 Acrylic resin plates 74a, 74b Hole 75 Hydrophobic part 76 Flow path 80 Lid 81 hole (Injection port) 82 Adhesive tape 83 Central part (hydrophilic part) 84 Paper double-sided tape 85 Flow path (micro flow path) 86 Hydrophobic part 90 Chip substrate 92 Transparent adhesive tape 93 Central part (hydrophilic part) 96 Hydrophobic part 100A-1 to 100E1, 100A-2 to 100E2
Chips E1, E2 Electrodes (electric drive) F _A sample fluid F _S sample fluid

Claims (7)

[Claims] 1. A microchannel chip comprising a microchannel having a cross section of a micro-equivalent diameter through which a liquid flows, and a low affinity portion having a lower affinity for the liquid than an inner wall surface forming the microchannel. Is provided on a part of the inner wall surface of the minute flow path, and the low affinity portion is constituted by an affinity changing member whose degree of affinity changes according to temperature change. Yes, a micro channel chip. 2. A microchannel system comprising the microchannel chip according to claim 1 and a liquid transporting means for transporting the liquid in the microchannel chip. 3. The microchannel system according to claim 2, wherein the liquid transporting means is constituted by pressure driving means that is driven by pressure. 4. The microchannel according to claim 2, wherein the liquid transporting means comprises the affinity changing member and temperature controlling means for controlling the temperature of the affinity changing member. system. 5. The liquid transporting means comprises a pair of electrodes mounted in the flow path and a voltage control means for controlling a voltage between the electrodes.
The microchannel system according to claim 2. 6. A microchannel comprising a microchannel chip having a microchannel of a cross section having a microscopic equivalent diameter through which a liquid flows, and a liquid transporting means for transporting the liquid in the channel. In the system, a low affinity portion having a lower affinity for the liquid than the inner wall surface forming the minute flow path is provided in a part of the inner wall surface, and the liquid transporting means is attached in the flow path. A microchannel system comprising a pair of electrodes and a voltage control means for controlling a voltage between the electrodes. 7. The microchannel system according to claim 2, wherein the step of introducing the liquid into the microchannel and the low-affinity portion provided in the microchannel are provided in the microchannel. And a step of restarting the transportation of the liquid in the flow path after the liquid has stopped flowing, a flow control method in a microchannel chip.