JP2006239538A - Microchannel and microchip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a microchannel and a microchip capable of realizing an accurate analysis with a small amount of sample without being affected by generation of bubbles due to gas dissolved in a sample. Objective.
A micro-channel for flowing a liquid, wherein a bubble nucleus is introduced into at least a part of an inner surface of the micro-channel from a gas existing in the channel into the liquid stream. A microchannel comprising means. As a result, regardless of the size of the microchannel, even if the amount of sample is very small, the gas that is excessively dissolved in the liquid sample is efficiently absorbed by the bubble nuclei generated by the bubble nuclei introduction means. It is possible to prevent the generation of bubbles at positions other than the bubble nucleus introducing means. As a result, accurate and rapid measurement and detection can be realized without disturbing the measurement system without disturbing the flow of the fluid.
[Selection] Figure 1

Description

  The present invention relates to a microchannel and a microchip, and relates to a microchannel used for separating, mixing, and detecting a biological substance and a microchip including the microchannel.

  In recent years, in the fields of medicine, food, drug discovery, biological materials such as DNA, enzymes, proteins, viruses, cells, clinical analysis chips, environmental analysis chips, gene analysis chips (DNA chips), protein analysis chips (proteome chips) ) In recent years, a technology called Lab on Chip that separates, reacts, mixes, measures and detects on a substrate of several centimeters size called a sugar chain chip, chromatographic chip, cell analysis chip, pharmaceutical screening chip, etc. Attention has been paid.

This chip is provided with a flow path of several nm to several mm, in which a small amount of fluid (including gas, liquid, fine particles, gel substance, etc.) is moved, reacted, measured, etc. Realized. Such a chip is generally called a microchip, and a channel on the chip is called a microchannel.
By pouring a small amount of sample, such as a blood sample, into such a microchip, various measurements, detections, and the like can be easily performed in a short time.

  However, samples, reagents, and the like used for the microchip are usually stored at a low temperature in advance, and the temperature is increased when measurement is performed using the microchip. As the temperature rises, the saturation solubility of gas components such as oxygen and nitrogen dissolved in the sample decreases, and the gas component dissolved above the saturation solubility is, for example, in the microchip. Generated as bubbles in the road. As a result, the air bubbles partially block the micro flow path, particularly the entire flow path, impeding fluid flow and impairing fluid controllability. In addition, when a microchip is used to measure the volume of the sample, it is difficult to accurately measure the volume of the sample due to the generation of bubbles. Furthermore, when a sample is quantified or qualitatively using an optical system, scattering of light is caused by bubbles and accurate measurement cannot be performed. Further, even when a sample is quantified or qualitatively using an electrode, if bubbles are generated on the electrode, accurate measurement cannot be performed.

Usually, in the field of spectroscopic measurement, in order to prevent the generation of bubbles from the solution, pre-treatment for removing dissolved gas from the solution and suppressing the generation of bubbles, such as heating and stirring the sample and ultrasonic stirring, is performed. ing.
However, in the case of using a microchip, the sample itself is a very small amount, and it is difficult to perform these pretreatments for the purpose of simple and rapid measurement, so that bubbles are sufficiently generated from the solution. It cannot be prevented.

On the other hand, a groove having a width of 300 μm and a depth of 100 μm parallel to the liquid flow direction in the microchannel at the bottom of the microchannel (width: 700 μm, depth: 500 μm) included in the microchip. A method has been proposed in which bubbles generated in a sample are collected in this groove and moved by a liquid flow to be discharged (for example, Non-Patent Document 1).
Technology and application of micro chemical chip, Maruzen, 2004, p160-p161

  However, depending on the size of the micro flow path, such a groove may not be formed at the bottom thereof, and the application of the groove becomes more difficult due to the minute amount of the sample and the miniaturization of the microchip. In addition, there is a problem that the flow of the sample is disturbed by the groove disposed in the center of the microchannel. Furthermore, since the bubbles collected in the groove are finally discharged out of the channel, the groove is formed over most of the extending direction of the microchannel. For this reason, the bubbles collected in the groove are coupled to each other. However, it becomes too large and is detached from the groove and floats in the sample. As a result, the bubbles disturb the flow of the sample and interfere with the measurement system, resulting in a situation where accurate measurement cannot be performed.

In other words, the formation of a groove parallel to the liquid flow direction in the microchannel does not prevent the measurement system from being disturbed by bubbles, and the original purpose of the microchip is achieved, which is to obtain accurate analysis results quickly with a small amount of sample. There is a need to be able to.
Accordingly, an object of the present invention is to provide a microchannel and a microchip capable of realizing an accurate analysis with a small amount of sample without being affected by bubbles generated by gas dissolved in the sample. And

The present invention relates to a microchannel for flowing a liquid, and introduces bubble nuclei into a liquid flow from at least a part of the inner surface of the microchannel into the liquid stream. Means are provided.
Thus, since at least a part of the inner surface of the microchannel is provided with bubble nucleus introduction means for introducing bubble nuclei from the gas existing in the channel into the liquid flow, When the sample is introduced, the cell nucleus can be introduced easily, simply and reliably. As a result, even if the temperature of the liquid sample flowing in the microchannel rises and the solubility of the gas in the liquid decreases, the excess gas is absorbed by this bubble nucleus. Generation of bubbles at the position can be prevented. As a result, the flow of the liquid flow is not disturbed by the bubbles, and the measurement can be prevented from being disturbed by the bubbles.

In this microchannel, the bubble nucleus introduction means may be configured to include a surface inclined with respect to the liquid flow direction and / or the bubble nucleus introduction means may be constituted by a plurality of independent recesses. preferable.
As a result, the bubble nucleus introduction means can be simply and effectively arranged on the inner surface of the microchannel, and the introduction of bubble nuclei and the suppression of the generation of bubbles other than the excessively dissolved gas bubble nucleus introduction means Can be performed more reliably.

Further, the bubble nucleus introducing means may be formed on the entire inner peripheral surface of the microchannel at a predetermined position in the longitudinal direction of the microchannel, or formed on a part of the inner peripheral surface of the microchannel. May be.
When the bubble nucleus introducing means is formed on the entire inner surface of the micro flow channel, the bubble nucleus can be appropriately introduced into the liquid flow, so that the micro contact with the liquid regardless of the position in the liquid flow. Efficiently absorbs and removes excessively dissolved gas on the entire surface of the flow path with bubble nuclei. Thereby, it is possible to reliably prevent the measurement from being disturbed by the generation of bubbles other than the bubble nucleus introducing means. Further, when it is formed on a part of the inner surface of the flow path, the gas that is excessively dissolved in the liquid is efficiently absorbed by the appropriate bubble nuclei, and from the bubble nucleus introduction means to the inner surface of the flow path. Even in the state where the bubbles are grown, it is possible to prevent the light path used in the measurement of the optical system from being blocked by the bubbles, which is useful for more accurate sample detection and measurement.

The microchip of the present invention includes the above-described microchannel.
As a result, in various fields such as medicine, food and drug discovery, various biological materials such as DNA, enzymes, proteins, viruses and cells are in a liquid state, clinical analysis chip, environmental analysis chip, gene analysis chip (DNA Chip), protein analysis chip (proteome chip), sugar chain chip, chromatographic chip, cell analysis chip, pharmaceutical screening chip, etc. Measurement, detection, etc. can be performed more quickly and accurately without receiving.

  According to the present invention, regardless of the size of the microchannel, the gas that is excessively dissolved in the sample in the liquid state is introduced into the bubble nuclei introduced into the bubble nuclei introduction means even in a small amount of sample. It is possible to efficiently absorb and prevent the generation of bubbles other than the bubble nucleus introducing means. As a result, accurate and rapid measurement and detection can be realized without disturbing the measurement system without disturbing the flow of the fluid.

(1) Microchannel configuration The microchannel has a desired shape two-dimensionally and / or three-dimensionally so that a sample (liquid or gas, preferably liquid) can pass therethrough. It is formed inside.
The planar shape of the microchannel is not particularly limited, and can be arbitrarily set in consideration of use, size, and the like. The cross section of the microchannel (cross section perpendicular to the fluid flow direction) is, for example, a polygon such as a quadrangle or trapezoid, and rounded corners, round, oval, dome, or left / right asymmetry Any shape such as a non-uniform shape may be used. The microchannel is for flowing a small amount of sample, preferably a liquid sample, and its size and length are not particularly limited as long as the purpose is appropriately achieved. The thing of about 0.0001-1mm < ² > and length is about 10-100mm is mentioned. In particular, as the cross-sectional area of the channel decreases, the flow of fluid in the micro-channel and the influence of bubbles generated in the fluid increase, so the cross-sectional area of the micro-channel is 0.0001 to 0.25 mm ^2. The present invention is advantageous to the extent. The microchannels may have the same cross-sectional shape and size over the entire length, but may have partially different shapes and sizes. For example, the part where the sample is introduced and / or discharged is not in a state where the microchannel is completely sealed, and a part of the upper part may be open, or the part for measuring the volume or the optical system In the detection unit or the like that performs measurement using the above, it is only necessary to maintain a constant cross-sectional area, and there may be a portion that gradually or gradually becomes thinner or thicker.

  The inner surface of the microchannel is provided with bubble nucleus introduction means for introducing bubble nuclei from the gas existing in the channel into the liquid flow. When the liquid is introduced into the microchannel, the bubble nucleus introducing means does not extrude a part of the gas present in the microchannel by the liquid, but forms bubbles on a part of the inner surface of the microchannel. Means which can stay and consequently introduce bubble nuclei into the inner surface of the microchannel. In order to perform the function of the bubble nucleus introducing means, it is considered that the wettability of the material constituting the bubble nucleus to the sample greatly influences, but in the present invention, the liquid is allowed to flow into the microchannel by appropriate wettability. When being introduced into the microchannel, a part of the gas present in the microchannel can be introduced as a bubble nucleus. That is, it means a means capable of intentionally introducing bubble nuclei in advance at the time of liquid introduction. This bubble nucleus introduction means not only introduces bubble nuclei, but also efficiently absorbs the gas dissolved excessively in the liquid flow into the bubble nuclei introduced into the bubble nucleus introduction means, and the absorbed gas Also has a function of holding together with the bubble core.

  Normally, large energy exceeding a certain energy barrier is required to generate bubbles from a liquid, but bubbles that already exist absorb the gas dissolved in the surrounding liquid and expand. In case you don't need energy. Further, when a liquid is flowed through the flow path, bubbles are likely to be generated at corners and recesses. Therefore, the bubble nucleus introducing means seems to combine the phenomenon and function of individual bubbles at first glance, thereby realizing the removal of bubbles.

The bubble nucleus introducing means may be of any form as long as such a function can be ensured. Specifically, the recessed part formed in the microchannel inner surface is mentioned.
In this way, not only the function of introducing bubble nuclei, but also the function of absorbing and holding dissolved gas, the introduced bubble nuclei grow by absorbing excessively dissolved gas in the liquid. It is possible to reduce the gas dissolved in the liquid while preventing the generation of bubbles other than the bubble nucleus introducing means. In particular, even if there is no flow in the liquid once introduced or the flow is small, the gas dissolved in the liquid is bubble nuclei whose dissolved gas concentration is reduced due to absorption of dissolved gas by the bubble nuclei due to concentration diffusion It will be drawn to the periphery, and it becomes possible to control the generation and remaining position of bubbles efficiently. Furthermore, normally, when a sample is introduced into a microchip, a deaeration process is performed. However, when such a bubble nucleus introduction means is formed, such a process can be omitted. Therefore, it can be used more quickly and easily.

  Regarding the position where the bubble nucleus introducing means is provided, the material constituting the bubble nucleus introducing means, the size (width), depth, density, shape, etc. of the recess constituting the bubble nucleus introducing means, the size, length, In consideration of securing the above-described functions by the material constituting this, the type of sample applied to the microchannel, the concentration, the viscosity and the volume, the position of the microchannel on the microchip and the intended action, etc. It can be selected appropriately.

  The position where the bubble nucleus introducing means is provided may be a part of a predetermined length in the longitudinal direction, or a plurality of the positions may be provided over the entire length. For example, if it is a flow path that merely moves the sample, it may be a part of the predetermined length, only a part of the inner periphery thereof, or the entire inner peripheral surface. Specifically, when the cross-sectional shape of the channel is a quadrangle, it is disposed on the entire upper and lower surfaces and left and right side surfaces, and on the entire surface including the curved surface from the upper side to the lower side if it is circular or dome-shaped. Is preferred. In addition, if the optical path of the optical system needs to be secured or the upstream side directly connected to these parts, the so-called detection part and the flow path in the vicinity thereof, the part is arranged only in a part of the inner periphery. Preferably it is. Specifically, when the cross-sectional shape of the channel is a square, if the cross-sectional shape is circular or dome-shaped from the entire left and right side surfaces, only above the both side surfaces, or from the center to the top, it is possible to ensure an optical path and the like. In addition, it is preferable that only the side surface, only the upper shoulder portion, or only from the center to the upper shoulder portion are arranged.

  As the material for the bubble nucleus introducing means, the same material as that constituting the microchannel, or the same material as that constituting the microchip can be used, or a different material can be used. For example, PET (polyethylene terephthalate, PDMS (polydimethylsiloxane), PMMA (polymethyl methacrylate), PC (polycarbonate), PP (polypropylene), PS (polystyrene), PVC (polyvinyl chloride) depending on the method of producing them. ), Organic compounds such as polysiloxane, allyl ester resin, cycloolefin polymer, Si rubber, or inorganic compounds such as Si, Si oxide film, quartz, glass, and ceramic.

Moreover, when the cross-sectional area of the microchannel to which the bubble nucleus introducing means is applied is, for example, about 0.01 to 10 mm ² , the width and / or depth of the recess is 0.1 to 1000 μm, preferably Tens of μm or more, 50 μm or more, 100 μm or more, tens of μm or less, and / or hundreds of μm or less. In particular, the width of the recess is preferably 1 to 1000 μm, more preferably about 30 to 500 μm. By setting to such a size, in consideration of the wettability of the sample with respect to the material of the bubble nucleus introduction means, it is possible to reliably introduce the bubble nucleus, and to capture the gas in the sample in the bubble nucleus, And a bubble can be hold | maintained in a bubble nucleus introduction means. In addition, if the depth (depth) of a recessed part is about 30-500 micrometers (more preferably about 50-300 micrometers), it will not disturb the flow of a sample with the bubble trapped there, but will also be subjected to the pressure load by a liquid flow. Nevertheless, the trapped bubbles can be attached. In addition, the collected bubbles do not scatter the light irradiated to the microchannel and adversely affect the measurement or the like.

Further, the density (number) of the recesses can be determined in consideration of the volume of bubble nuclei formed when the liquid is introduced and the total amount of gas contained in the liquid introduced into the microchannel. When the liquid is introduced, bubble nuclei generated in the recess occupy 5 to 90% of the volume in the recess. The amount of gas generated when the liquid is heated from 0 ° C. to 40 ° C. is about 1.7% (volume ratio) of the liquid amount. Therefore, in order to hold all the gas that has become excessive when the liquid temperature rises in the recess, the total volume of the recess is preferably set to be about 1.8 to 17% of the liquid volume. Specifically, the total volume of the recesses is set to be about 0.088 to 0.83 mm ³ with respect to the channel having a volume of 4.9 mm ³ (width 700 μm × height 700 μm × length 10000 μm). Is preferred. If the size (cross-sectional area × depth) of one recess is about 100 μm ² × 100 μm, the density (number) of recesses is about 9 to 90, and the size (cross-sectional area × depth) of one recess. Is about 500 μm ² × 400 μm, about 1 to 5 pieces are required. For example, about 4 pieces, about 6 pieces, about 10 pieces, and about 20 pieces may be used.

  The shape of the concave portion is not particularly limited, and is hemispherical; semi-elliptical; rectangular parallelepiped, cubic or polygonal prism; dome shape; conical shape such as cone, triangular pyramid, quadrangular pyramid; frustum Shape: non-symmetrical non-uniform shape; shape having taper in width direction, height direction and / or depth direction; any shape such as a combination thereof. However, it is preferable that the recessed part is formed with an independent recessed part (for example, see FIGS. 3A to 3E). That is, although some recessed parts may be formed so that it may continue, it is preferable that most of the recessed parts are independently formed individually. It is considered that if the number of continuous recesses increases, the trapped bubbles come into contact with each other and grow easily into large bubbles, and the bubbles are easily re-released into the fluid.

  In particular, it is preferable that the bubble nucleus introducing means includes a surface inclined with respect to the liquid flow direction (arrow in FIG. 3). In this case, the inclination angle (see θ in FIG. 3B) is the property of the material constituting the microchannel, the depth, width, density, shape of the recess itself, the type of sample applied to the microchannel, The concentration, viscosity, wettability, etc. can be taken into account for appropriate adjustment. For example, a range of about several degrees to 160 degrees can be mentioned, and it is preferable to exceed 90 degrees. From another viewpoint, it is preferable that the bubble nucleus introducing means includes two surfaces (which may be rounded surfaces corresponding to the two surfaces) having an acute angle in cross-sectional shape. Thereby, it is possible to reliably introduce the bubble nuclei irrespective of the viscosity of the sample to be applied. In addition, when the inclined surface of the bubble nucleus introducing means is a curved surface or the like, the surface including the tangent line of the curved surface may be inclined at an angle.

The recesses may have the same width and / or depth, density, shape, etc. throughout the microchannel, but may be partially different or nonuniform in the microchannel.
(2) Manufacturing method of microchannel The microchannel can be easily manufactured by using a method known in the art. For example, a mold having a shape corresponding to a desired microchip, microchannel, and bubble nucleus introducing means is prepared. This mold can be formed by mechanical processing. In particular, the mold portion of the portion forming the bubble nucleus introducing means is in a region intended to form a microchannel, What was processed so that it may have a shape corresponding to a bubble nucleus introduction | transduction means by means, such as a blast process and a grinding | polishing process, is preferable. Next, PET is molded into this mold to obtain a substrate on which the pattern corresponding to the microchannel and the cell nucleus introducing means are transferred. Finally, two substrates are bonded to each other so that the patterns face each other, thereby forming a microchip having a microchannel in which bubble nucleus introducing means is formed at a desired position. In addition, it is good also considering only the board | substrate which has a pattern corresponding to a micro flow path as one side, and a flat plate board | substrate.

Further, instead of molding using a mold, an injection molding method or an imprint method may be used.
Furthermore, one or both of the flat substrates may be directly subjected to a photolithography process, mechanical processing, or the like to obtain a substrate on which a pattern corresponding to the microchannel is transferred.
Further, in the substrate having a pattern corresponding to the microchannel, the concave portion may be formed directly on the portion where the bubble nucleus introducing means is formed by a physical method such as blasting, polishing or glow discharge. The recess may be formed by etching with an alkali-dissolved salt or a fluorine chemical, coating with a film, or the like.
(3) Configuration of a microchip provided with a microchannel For example, a microchip mainly includes a first substrate and a second substrate having variously shaped patterns on one or both sides, for example, thermocompression bonding and adhesion. It is configured to be bonded with an agent or the like.

  Such microchips analyze, detect, react, and analyze various biological materials (mainly in a liquid state) such as DNA, enzymes, proteins, viruses, and cells in various fields such as medicine, food, and drug discovery. Used as a substrate for measurement, such as clinical analysis chip, environmental analysis chip, gene analysis chip (DNA chip), protein analysis chip (proteome chip), sugar chain chip, chromatographic chip, cell analysis It includes all chips provided under various names such as chips, pharmaceutical screening chips and the like.

Such a microchip includes a microchannel having a linear or bent or curved pattern of various two-dimensional and / or three-dimensional shapes as described above depending on the application. In addition, a sample introduction port, a discharge port, and / or a liquid reservoir are formed at the end or in the middle of the microchannel, and a centrifuge unit, a metering unit, a mixing reaction unit, optical or electrical measurement, and the like. The parts and the like are formed in a series structure as themselves or as microchannels connecting them.
<Example 1>
As shown in FIGS. 1A and 1B and FIG. 2, the microchannel and microchip of the present invention are provided on the surface of a substrate made of two PET sheets having a thickness of 1 mm. Are formed by the substrates 11 and 12 having a pattern corresponding to. The substrates 11 and 12 can be formed by molding using a mold. In this way, the substrates 11 and 12 having the patterns of the microchannels 14 and 34 are bonded to each other with the patterns facing each other through the adhesive 13, for example, so that the microchannels 14 and 34 are formed inside. The formed microchip 10 is obtained.

  In the microchip 10, for example, first, a sample is introduced from the sample introduction port 20. The introduced sample passes through the centrifugal separator 21 and moves to the liquid reservoir 22 by a centrifugal force or the like obtained by rotating the microchip 10. The sample passes from the liquid reservoir 22 through the microchannel 14 to the measurement unit 26 of the optical system. Here, for example, light irradiation is performed, the number of cells is counted, and the absorbance is measured.

As shown in FIGS. 1A and 1B, the microchannel 34 transmits light to the microchannel 34 at a position corresponding to the measurement unit, and the component concentration in the sample is determined by the transmittance. The width is set to 700 μm, the depth is 700 μm, and the length is 10 mm.
At the top of both side surfaces inside the microchannel 34, there are eight fine concave portions of a triangular pyramid each having a width × height × depth of about 700 μm × 300 μm × 700 μm as a bubble nucleus introducing means 35 on each side. , With a spacing of 1000 μm. One surface constituting the bubble nucleus introducing means 35 has inclined surfaces of θ = about 60 ° and θ ′ = 120 ° with respect to the direction in which the sample flows.

  The reagent and sample stored at 4 ° C. are injected into the microchip from the inlet 20, and the entire microchip is heated to 37 ° C. to promote the reaction between the reagent and the sample, and the sample is moved. I let you. When the sample passes through the part of the bubble nucleus introducing means 35, the gas existing in the microchannel 34 remains, and the bubble nucleus is introduced into the corner part of the bubble nucleus introducing means 35, and the solubility decreases due to temperature rise. It was confirmed that the excess gas was absorbed by the introduced bubble nuclei and no bubbles were generated in portions other than the bubble nuclei introducing means 35. It was also confirmed that the bubble nuclei grown in the bubble nuclei introducing means 35 surely stayed in this recess.

As a result, when the microchannel 34 is irradiated with light having a width of 300 μm from the outside and the component concentration in the sample is detected by the transmittance, all bubbles are generated in the bubble nucleus introducing means 35, and the detection light 17 Since no bubbles are generated in the part where the air passes, accurate detection can be performed without being subjected to irregular reflection of light by the bubbles.
<Examples 2 to 6>
As shown in the plan views of FIGS. 3A to 3E, the microchannel of this embodiment is the same as the microchip shown in FIG. It was formed in the same manner as in Example 1 except that 35e was changed to various shapes.

In this microchip, the same effect as in Example 1 was obtained.
<Example 7>
As shown in FIGS. 4 (a) and 4 (b), the microchannel of this example was a quadrilateral sectional shape having a width of 100 μm and a depth of 100 μm, as shown in FIGS. On the upper and lower surfaces and both side surfaces of the inner surface of the microchannel 24, fine concave portions having a width and a depth of about 1 μm are partially formed as a bubble nucleus introducing means 15 at a density of 10,000 / mm ^2. Yes.

Reagents and samples stored at 4 ° C. were injected into the microchip from the inlet 20. In order to promote the reaction between the reagent and the sample, the entire microchip was heated to 40 ° C.
At this time, the gas component corresponding to the amount of change in the saturation solubility with respect to the temperature change elutes to become bubbles, but when the liquid flows through the microchannel 24, it exists in the microchannel 24 by the bubble nucleus introducing means 15. The gas to be trapped in the recess by the liquid became bubble nuclei. This introduced bubble nucleus absorbs the gas that is excessively dissolved in the liquid and reduces the gas that is excessively dissolved in the liquid while growing, preventing the generation of bubbles other than the means for introducing the bubble nucleus To do. As a result, bubbles were generated only in the bubble nucleus introducing means, and the generated bubbles were stably held in the bubble nucleus introducing means. The gas in which the liquid is dissolved absorbs the dissolved gas by the bubble nuclei by concentration diffusion, and moves to the periphery of the bubble nuclei where the dissolved gas concentration is lowered, and efficiently controls the generation of bubbles and the remaining position. I was able to.

Accordingly, the sample can be moved smoothly without disturbing the flow of the sample. For example, the sample measured by the measuring unit 23 can be accurately measured because no bubbles are mixed therein. It was.
<Example 8>
The microchannel of this embodiment transmits light to the microchannel 14 at the position corresponding to the measurement unit in the microchip shown in FIG. 2 as shown in FIGS. 5 (a) and 5 (b). Thus, the width is set to 300 μm, the depth is 100 μm, and the length is 10 mm so that the component concentration in the sample can be detected by the transmittance.

On both side surfaces inside the microchannel 14, fine concave portions having a width and a depth of about 1 μm are partially formed at a density of 60000 pieces / mm ² as the bubble nucleus introducing means 15.
The reagent and sample stored at 4 ° C. were injected into the microchip from the introduction port 20, and the entire microchip was heated to 40 ° C. in order to promote the reaction between the reagent and the sample.
At this time, the gas component corresponding to the amount of change in the saturation solubility with respect to the temperature change is vaporized to form bubbles. However, when the liquid flows through the microchannel 24, it is present in the microchannel 24 by the bubble nucleus introducing means 15. The gas to be trapped in the recess by the liquid became bubble nuclei. This introduced bubble nucleus absorbs the gas that is excessively dissolved in the liquid and reduces the gas that is excessively dissolved in the liquid while growing, preventing the generation of bubbles other than the means for introducing the bubble nucleus Therefore, bubbles were generated only in the bubble nucleus introducing means, and the generated bubbles were stably held in the bubble nucleus introducing means. The gas in which the liquid is dissolved moves to the periphery of the bubble nucleus where the dissolved gas concentration is lowered by absorption of the dissolved gas by the bubble nucleus due to concentration diffusion, and the generation of bubbles and the residual position can be controlled efficiently. did it.

Thereby, when the microchannel 14 is irradiated with light having a width of 50 μm from the outside and the component concentration in the sample is detected by the transmittance, the diffuse reflection of light due to the bubbles 16 entering the optical path 17 is effectively prevented. And was able to perform accurate detection.
<Example 9>
In the microchannel of this embodiment, in the microchip shown in FIG. 2, light is transmitted through the microchannel at a position corresponding to the measurement unit, and the component concentration in the sample is detected by the transmittance. The width is set to 300 μm, the depth is 100 μm, and the length is 10 mm.

Bubble nucleus introduction means are partially formed at a density of 2000 / mm ^{2 on} both side surfaces inside the microchannel. One of the bubble nucleus introducing means is shown in FIG. The bubble nucleus introducing means 45 has a curved surface approximated by a sine wave having a width λ and a depth 2a on the side surface of the microchannel 44 formed of PET. Further, the liquid sample 40 to be introduced is constituted by a mixture of the reagent and the plasma relative to the microchannel 44, the contact angle theta _a is introduced at about 100 °.

In this case, the condition for introducing bubble nuclei is expressed by a> λ · (absolute value of tanθ _a ) / 2π (see Yoshioka Shoten “Physics of Surface Tension” 2003, p221 to p222), and means for introducing bubble nuclei The relationship between the width and the depth is expressed by a> 0.91λ.
Therefore, when the width of the bubble nucleus introducing means is 1 μm, 10 μm, 100 μm and 1000 μm, respectively, the depth is set to be larger than 1.82 μm, larger than 18.2 μm, larger than 182 μm and larger than 1820 μm. In addition, it is possible to reliably introduce the bubble nucleus into the bubble nucleus introduction means.

  As a result, the temperature of the liquid sample is raised by about 40 ° C., and the microchannel is irradiated with light having a width of 50 μm from the outside, and the component concentration in the sample is detected by the transmittance as described above. Thus, irregular reflection of light due to bubbles entering the optical path can be effectively prevented, and accurate detection can be performed.

  The present invention relates to a clinical analysis chip, an environmental analysis chip, a gene analysis chip (DNA chip), a protein analysis chip (proteome chip), a sugar chain chip, a chromatographic chip, used in the fields of medicine, food, drug discovery, etc. It can be used for various substrates that can be applied to gases and liquids called cell analysis chips and pharmaceutical screening chips.

The top view and sectional drawing which show one Embodiment of the microchannel of this invention. The top view of a microchip provided with the microchannel of FIG. The top view and sectional drawing which show another embodiment of the microchannel of this invention. The top view which shows another embodiment of the microchannel of this invention. The top view and sectional drawing which show another embodiment of the microchannel of this invention. Sectional drawing for demonstrating the conditions for introduce | transducing a bubble nucleus into a bubble nucleus introduction means in the microchannel of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Microchip 11, 12 Board | substrate 13 Adhesive 14, 24, 34, 44 Micro flow path 16 Bubble 17 Optical path 20 Inlet 21 Centrifugal part 22 Liquid reservoir 26 Measuring part 15, 35, 45 Bubble nucleus introduction means 40 Liquid sample

Claims (6)

A micro-channel for flowing a liquid, comprising at least a part of an inner surface of the micro-channel having bubble nucleus introduction means for introducing bubble nuclei from a gas existing in the channel into the liquid stream A microchannel characterized by comprising: The microchannel according to claim 1, wherein the bubble nucleus introducing means includes a surface inclined with respect to the liquid flow direction. The microchannel according to claim 1 or 2, wherein the bubble nucleus introducing means is constituted by a plurality of independent recesses. The microchannel according to any one of claims 1 to 3, wherein the bubble nucleus introducing means is formed on the entire inner peripheral surface of the microchannel at a predetermined position in the longitudinal direction of the microchannel. The microchannel according to any one of claims 1 to 3, wherein the bubble nucleus introducing means is formed on a part of the inner peripheral surface of the microchannel at a predetermined position in the longitudinal direction of the microchannel. A microchip comprising the microchannel according to any one of claims 1 to 5.