JP2006075679A - Two-phase flow stabilizing chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To stabilize a two-phase flow formed in the flow channel in a microchip. <P>SOLUTION: Grooves different in cross-sectional area are respectively formed to the surfaces of two substrates and the groove forming surfaces of both substrates are laminated to form a flow channel having a protruded cross section, which comprises flow channel parts different in cross-sectional area, in the chip. When two kinds of solvents different in properties are allowed to flow to the flow channel from an introducing port. The interface of the two-phase flow is rotated by 90° to become parallel to the bonded surface of the chip and the two-phase flow is stabilized. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention extracts a substance in a minute amount of solution, for example, a microorganism, protein, nucleic acid, carbohydrate, antigen, antibody or a mixture of these, or stabilizes a two-phase flow in order to perform a chemical reaction or analysis. It relates to the device.

  In recent years, in the field of analytical chemistry, research on μTAS (Micro Total Systems) has been actively conducted, and it is expected to use a microchip to achieve high-speed analysis, sample saving, and solvent saving. In the reaction in the micro space on the microchip, there is a possibility that the reaction efficiency can be improved as compared with the reaction using the conventional chemical operation. When a chemical process or equipment is used at a micro size, the interface area per unit volume (called specific interface area) at which a chemical reaction occurs is larger than at a macro size, so it occurs at the liquid-liquid interface. The efficiency of the phenomenon is increased. Further, the liquid flowing through the microchannel due to fluid dynamics has a small Reynolds number because the flow path is fine, and two layers parallel to the same direction as the flow are easily formed.

  For example, when extraction is performed between two liquids such as water and phenol that are not mixed, and the flow path has a normal size, the liquid has a small specific interface area that becomes a reaction field if it remains in two layers, but it is disadvantageous. When the space size of the path is small, the diffusion distance is shortened and the specific interface area of the reaction is also large. Therefore, it is not necessary to perform mechanical mixing, and mixed extraction can be performed only by molecular diffusion.

Until now, in order to stabilize the two-phase flow in the flow channel (microchannel), a method of providing a groove-shaped guide on the bottom surface (see Non-Patent Document 1), or a method of providing a broken-line guideline on the bottom surface (Non-Patent Document). Reference 2)), and a method of hydrophobic treatment by chemical modification with a toluene solution of octadecyltrichlorosilane (see Non-Patent Document 3) has been taken. However, a method of allowing a two-phase flow to flow stably by a simpler method is desired.
For example, a centrifugal separation method is generally used to separate the emulsion. Recently, as a method of separating an emulsion in a microchannel, a method of phase separation through an emulsion through a flow path formed by bonding a hydrophilic substrate and a hydrophobic substrate has been reported (see Non-Patent Document 4). A method of separating the emulsion by a simpler method is desired.
Anal. Chem., 74, 1565-1571 (2001) Proceedings of the 7th Chemistry and Micro-Nano System Research Meeting P52 2P08 Proceedings of the 7th Chemistry and Micro-Nano System Research Meeting P59 2P15 The 7th International conference on Microreaction Technology, Proceedings P41

In general, in a microchannel, a two-phase flow is likely to be formed because the Reynolds number is small, but depending on the type of the solvent, a two-phase flow may be difficult to form due to the viscosity of the solvent or the surface tension with the channel surface. Examples include dichloromethane / water, chloroform / water, n-hexane / water, and the like. That is, it is difficult to carry out solvent extraction by carrying out interphase molecular transport in a microchannel using these solvents because the interface becomes unstable and becomes a plug flow.
An object of the present invention is to form a stable two-phase flow in a microchip with a simple flow path shape or to enable phase separation of an emulsion.

In the present invention, in a chip having a channel having a cross-sectional shape with a width and depth of 1 mm or less in the substrate, the cross-sectional shape orthogonal to the flow direction of the channel is joined by the first and second convex shapes. The two-phase flow stabilizing chip has a convex shape, and the first cross-sectional shape is larger in cross-sectional area and width than the second cross-sectional shape.
It is preferable that the inner surface of the channel portion having the first cross-sectional shape is hydrophilic and the inner surface of the channel portion having the second cross-sectional shape is hydrophobic.
As one method for that purpose, one or both of the inner surface of the channel portion having the first cross-sectional shape and the channel portion having the second cross-sectional shape can be chemically modified to be hydrophilic or hydrophobic.
As another method, the flow channel portion having the first cross-sectional shape may be formed on the hydrophilic substrate, and the flow channel portion having the second cross-sectional shape may be formed on the hydrophobic substrate.
A two-phase flow stabilization chip can be provided by having two liquid inlets and connecting a liquid inflow path connected to the liquid inlets to the flow path.

  When the emulsion is allowed to flow through the chip, phase separation can be achieved by forming a two-layer flow with a specific interface area.

The two-phase flow stabilization chip of the present invention is characterized in that the cross-sectional shape is convex, and the two-phase flow is stabilized with a simple structure due to the difference in specific interface area of the cross section of the flow path.
By chemically modifying the inner surface of the flow channel portion or using a substrate having hydrophilic or hydrophobic properties, the inner surface of the flow channel portion having the first cross-sectional shape becomes more hydrophilic, and the second cross-sectional shape It is possible to make the flow path portion having the hydrophobicity, and it is possible to further stabilize the two-phase flow.
In addition, gas-liquid interface stabilization can also be applied to synthesis reactions such as gas-liquid reactions using microchannels. Moreover, extraction operation can also be performed at the interface of a two-phase flow, and can be applied to phase separation of an emulsion or the like.
Since the structure of the present invention is a very simple structure and can be introduced into various chip manufacturing processes, it can be applied to complicated microchips incorporating valves and the like.
In this way, new technical means for highly integrated microchips and multilayer liquid formation in the microchips are provided.

  FIG. 1 shows an example of the cross-sectional shape of the flow path in the two-phase flow stabilization chip of one embodiment. As an example of the flow path in the chip, grooves 3a and 3b to be flow paths are formed on the respective substrates 2 and 4, and the two substrates are bonded to form a flow path by overlapping the grooves. (FIG. 1-A) and the groove | channel 9 used as the flow path which has flow-path part 9a, 9b from which cross-sectional shape differs in the board | substrate 7 of 1 sheet, and the flat board | substrate 5 is closed so that the opening of the groove | channel 9 may be closed. There is a method of bonding (FIG. 1-B).

FIG. 2 shows a manufacturing method of an embodiment (FIG. 1-A) produced by bonding two substrates each having a groove to be a flow path formed on each substrate (FIG. 1A).
(A) First, after the glass substrate 30 is washed, the photoresist 32 is coated.
(B) Next, the photoresist 32 is exposed to UV (ultraviolet) light using the photomask 34.
(C) Thereafter, the photoresist 32 is developed and patterned.
(D) Using the patterned photoresist 32 as a mask, the substrate 30 is etched with, for example, a 46% hydrofluoric acid aqueous solution to form the flow channel groove 36.
(E) The photoresist 32 is removed.
(F) Similarly, the flow path grooves having different cross-sectional sizes are formed on the other substrates, the surfaces of the both substrates on which the grooves are formed face each other, and the flow paths are formed by liquid-tight bonding with a hydrofluoric acid solution. 38 is formed.

  As a substrate material, a glass substrate, a silicon substrate, or a resin substrate can be used. In any case, a groove to be a flow path is formed on the bonding surface of the upper substrate and the lower substrate chemically, mechanically, or by various means such as laser irradiation or ion etching so that the grooves overlap. By sticking together, the convex channel proposed in the present invention can be created.

  The cross-sectional shape of the channel according to the present invention is a convex shape, and the first large cross-sectional shape and the second small cross-sectional shape are combined. FIG. 3 shows an example of the cross-sectional shape. Regarding the means for processing each cross-sectional shape, the triangular or trapezoidal portions shown in (B), (C), (D), (F), and (H) are obtained by anisotropic etching of the silicon substrate with alkali ( The portions having curves shown in E), (F), (G), and (H) are processed by wet etching, and the rectangles (A), (B), (C), (E), and (G) are used. Can be formed by anisotropic etching using dry etching.

One example is illustrated by FIGS. The upper substrate 2 and the lower substrate 4 serving as covers are, for example, quartz glass substrates. The upper substrates 2 and 4 are viewed from above. The substrate may be any material that can produce a flow path. On the contact surface side of the glass substrate 2 with the glass substrate 4, a channel groove 8 a (FIG. 5B) having a width of 100 μm and a depth of 40 μm and two introduction holes 10 for introducing liquid or gas. -1, 10-2 and a discharge hole 10-3 for discharge. The groove 8 meanders, one end branches into two near the introduction holes 10-1 and 10-2 and is connected to the introduction holes 10-1 and 10-2, and the other end is connected to the discharge hole 10-3. ing. The introduction holes 10-1, 10-2 and the discharge hole 10-3 are formed as through holes. On the contact surface side of the glass substrate 4 with the glass substrate 2, a channel groove 8 b (FIG. 5B) having a width of 300 μm and a depth of 40 μm is formed. The groove 8a and the groove 8b are formed symmetrically so as to overlap each other when facing each other. The groove forming surfaces of both the substrates 2 and 4 are brought into close contact with each other, and the flow paths are formed by, for example, liquid-tight bonding by means such as bonding with a hydrofluoric acid solution.
The width and depth of the flow path are examples, and both the width and depth can be changed.

The glass substrate 6 in FIG. 5A is obtained by bonding the groove forming surfaces of the glass substrate 2 and the glass substrate 4 face to face. A cross-sectional view of the flow path 8 is shown in FIG. The width 12-2 of the flow channel 8a is 100 μm, the width 12-3 of the flow channel 8b is 300 μm, the depth 12-4 of the flow channel 8a is 40 μm, and the depth 12-5 of the flow channel 8b is 40 μm. is there.
In such a flow path 8, when a gas is flowed from the introduction hole 10-1 and water is flowed from the introduction hole 10-2, easy-to-flow air flows through the flow path 8 a of the glass substrate 2 having the narrower flow path width. Since the difficult-to-flow water flows through the flow path portion 8b of the glass substrate 4, the fluid layer rotates 90 degrees in the flow path 8, and air flows through the flow path portion 8a of the glass substrate 2 and flows through the glass substrate 4. Water selectively flows through the path portion 8b.

The flow path of this chip is characterized in that the cross-sectional shape differs between the upper and lower substrates, but the two-phase flow in the flow path can be further stabilized by chemically modifying the inner surface of the flow path. . For example, there is a method of hydrophobic treatment by chemical modification (see Non-Patent Document 3) with a toluene solution of 10% octadecyltrichlorosilane, and there is also a method of hydrophilic treatment by a photocatalyst such as TiO ₂ . .

  As a means for stabilizing the two-phase flow, a hydrophobic or hydrophilic substrate can be used in addition to the chemical modification method. For example, it can be made hydrophilic by using a glass substrate and can be made hydrophobic by using PTFE (polytetrafluoroethylene) as a substrate.

  The means for stabilizing the two-phase flow described above can be combined. For example, a flow path is formed on a glass substrate by means of etching, and this is chemically treated and used as a hydrophilic substrate. A hydrophobic substrate in which a flow path is formed by etching on a fluoroethylene substrate can be used.

FIG. 6 shows a schematic diagram of stabilization of the two-phase flow according to the convex cross-sectional shape of the flow path. FIG. 6A shows a two-phase flow stabilization chip, which is shown in FIG. (B) shows the cross-sectional shape of the flow path 8 in the chip, and (C) is a plan view of the portion where the flow paths from the introduction holes 10-1 and 10-2 are joined. 1, 22-2 are shown. (E) is the cross-sectional shape of the part. (D) shows the two-layer flows 22-1 and 22-2 after 90-degree rotation of the layers has occurred after the flow paths merge. (F) is the cross-sectional shape of the portion, and shows that there is a layer flow 22-1 on the upper side.
For example, when ethyl acetate is flowed as the phase 22-1 and water is flowed as the phase 22-2, the phase in the flow path rotates 90 degrees as it moves from the surface view (C) to (D). It turns out that the second phase 22-1 rides on the phase 22-2, and the two-phase flow is stable by flowing through the flow paths having different cross-sectional areas.
4 and 5 can be various combinations such as air / water in addition to ethyl acetate / water.

One example of a chip diagram for performing emulsion separation is illustrated by FIGS. The upper substrate 2 and the lower substrate 4 serving as covers are, for example, quartz glass substrates. On the contact surface side of the glass substrate 2 with the glass substrate 4, a channel groove 11 a (FIG. 8B) having a width of 100 μm and a depth of 40 μm, an introduction hole 14-1 for emulsion introduction, and discharge A discharge hole 14-2 is formed. The groove 11 meanders, one end is connected to the introduction hole 14-1, and the other end is connected to the discharge hole 14-2. The introduction hole 14-1 and the discharge hole 14-2 are formed as through holes. On the contact surface side of the glass substrate 4 with the glass substrate 2, a channel groove 11 b (FIG. 8B) having a width of 300 μm and a depth of 40 μm is formed. The groove 11a and the groove 11b are formed symmetrically so as to overlap each other. The groove forming surfaces of both the substrates 2 and 4 are brought into close contact with each other, and the flow path is formed by, for example, liquid-tight bonding by means such as bonding with a hydrofluoric acid solution.
The width and depth of the flow path are examples, and both the width and depth can be changed.

The glass substrate 6 in FIG. 8A is obtained by bonding the groove forming surfaces of the glass substrate 2 and the glass substrate 4 face to face. A cross-sectional view of the flow path 11 is shown in FIG. The width 16-2 of the flow channel 11a is 100 μm, the width 16-3 of the flow channel 11b is 300 μm, the depth 16-4 of the flow channel 11a is 40 μm, and the depth 16-5 of the flow channel 11b is 40 μm. is there.
In such a channel 11, when water and oil emulsion is flowed from the introduction hole 14-1, the oil part that is easy to flow flows through the channel 11 a of the glass substrate 2 having a narrow channel width, and the water part that is difficult to flow Flows through the flow passage portion 11b of the glass substrate 4, so that the phase separation of the emulsion in the flow passage 11 occurs, the oil portion in the flow passage portion 11a of the glass substrate 2, and the water portion in the flow passage portion 11b of the glass substrate 4. Flows selectively.

  When separating the emulsion, it is possible to increase the separation performance by treating the inner surface of the flow path with a hydrophilic or hydrophobic chemical modification in the same manner as when the two-phase flow is stabilized. .

  When the two-phase flow stabilization chip according to the present invention is used, it can be used for a very small amount of liquid-liquid extraction and a very small amount of gas-liquid reaction. In addition, the emulsion can be separated.

(A), (B) is a channel sectional view of an example, respectively. It is process sectional drawing which shows the flow-path formation method by the etching method. (A)-(H) are examples of the convex cross-sectional shape of a flow path, respectively. It is a top view of the two board | substrates which comprise the microchip of one Example. It is a figure which shows the microchip of the Example, (A) is a top view, (B) is sectional drawing in the XX line position of (A). It is a schematic diagram when a phase rotates 90 degrees in a channel of a microchip, (A) is a plan view, (B) is a sectional view of the channel, and (C) and (D) are enlarged plan views. , (E) and (F) are sectional views of (C) and (D), respectively. It is a top view of two board | substrates which comprise the microchip of another Example. It is a figure which shows the microchip of the Example, (A) is a top view, (B) is sectional drawing in the XX line position of (A).

Explanation of symbols

2, 4, 5, 6, 7, 30 Glass substrate 3, 8, 9, 11 Channel 3a, 3b, 8a, 8b, 9a, 9b, 11a, 11b Channel portion 10-1, 10-2, 14- 1 Inlet 10-3, 14-2 Outlet

Claims (6)

In a chip having a channel having a cross-sectional shape with a width and depth of 1 mm or less in a substrate,
The cross-sectional shape perpendicular to the flow direction of the flow path is a convex shape in which the first and second convex shapes are joined,
The two-phase flow stabilizing chip, wherein the first cross-sectional shape has a larger cross-sectional area and width than the second cross-sectional shape.   The two-phase flow stabilizing chip according to claim 1, wherein the inner surface of the flow path portion having the first cross-sectional shape is hydrophilic, and the inner surface of the flow path portion having the second cross-sectional shape is hydrophobic.   3. The two-phase flow according to claim 1, wherein one or both of the flow path portion having the first cross-sectional shape and the inner surface of the flow path portion having the second cross-sectional shape are chemically modified to be hydrophilic or hydrophobic. Stabilization chip.   The flow path portion having a first cross-sectional shape is formed on a hydrophilic substrate, and the flow path portion having a second cross-sectional shape is formed on a hydrophobic substrate. Two-phase flow stabilization chip.   5. The two-phase flow stabilization chip according to claim 1, wherein the two-phase flow stabilizing chip has two liquid inlets and a liquid inflow path connected to the liquid inlets is connected to the flow path. The two-phase flow stabilization chip according to any one of claims 1 to 4, wherein the flow path has one liquid inlet.

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