JP2009090164A - Microchip device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchip device having the high functional liquid-liquid separation performance which has overcome the problems included in conventional techniques. <P>SOLUTION: In the microchip device with a mechanism that two types of immiscible liquids are introduced into a detailed passage via different passages and passed within the detailed passage while forming two-laminar flow in contact with each other via the interface in the detailed passage, and then withdrawn through the different divided passages again, the detailed passage is characterized in that it is formed by bonding a first sheet-like member and a second sheet-like member after drilling a gutter to at least one of them, the hydrophilic chemical treatment is effected to the inner wall of the flowing side of the hydrophilic liquid in the detailed passage and the hydrophobic chemical treatment is effected to the inner wall of the flowing side of the hydrophobic liquid so that two types of liquids flow as the two-laminar flow, and in that a partition member jutted so as to divide the two-laminar flow from both sides along the interface of the two types of liquids is installed to the side walls of the detailed passage. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a microchip device that is widely used for extraction and purification operations of trace substances in a complex mixture sample, for example, environmental pollutants such as agricultural chemicals in environmental water, drugs and proteins in biological samples, and the like.

  Research on solvent extraction technology using micro-channels of microchip devices has been actively conducted since it has the advantage that the specific interface area is larger than that of macro systems. In addition, according to fluid dynamics, the liquid flowing through the fine channel has a smaller Reynolds number (ratio of inertia force to frictional force due to viscosity), and the flow is stronger than the inertial action. Two parallel laminar flows are likely to be formed.

  Since the two-layer flow in such a fine channel is hardly affected by gravity, two kinds of liquids having different specific gravity (for example, water and ether) that are not mixed are brought into contact in the horizontal direction in the same direction. When flowing, a two-layer flow separated into left and right is formed.

  At this time, for example, if a large amount of hydrophobic contaminants and a small amount of hydrophilic substance (target substance) are dissolved in ether, the target substance moves from the ether layer to the aqueous layer while riding on the flow of the solvent. . And if the flow path which branches a water layer and an ether layer downstream is provided, it will become possible to extract a target substance.

  As described above, it is easy to form a parallel two-layer flow in the fine flow path. However, depending on the type of the solvent, a stable two-layer flow may be difficult to be formed 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.

  Until now, in order to stabilize the two-layer flow in the microchannel, for example, a method of providing a groove-shaped guide on the bottom surface of the microchannel (Patent Document 1), or a broken-line guide on the bottom surface of the microchannel A method of forming a groove (patent document 2) or a method of forming grooves with different depths and widths on two substrates, making the wall surface of each groove hydrophilic and hydrophobic, and forming a flow path by combining both grooves (patent document 2) 3) etc. have been taken.

Japanese Patent Laid-Open No. 2002-001102 JP 2005-034827 A Japanese Patent Laid-Open No. 2006-075680

  However, in the method of Patent Document 1, since the guide structure is formed only on the bottom surface of the flow path, there are limitations on combinations of solvents and the like in order to form a stable interface. In addition, it is technically difficult to use the inner wall of the channel together with chemical treatment.

  In addition, the method of Patent Document 2 has a high technical difficulty in producing a guide structure and is not suitable for practical use. Further, since the liquid-liquid contact area is reduced by the guide, the extraction efficiency is lowered. is there.

  In the method of Patent Document 3, chemical treatment of the inner wall of the flow path is easy. However, if the cross-sectional shapes of the upper and lower flow paths are equal, the effect of stabilizing the interface is reduced, so that the liquid-liquid flow rates are equal. There is a problem that it is difficult to use.

  On the other hand, when looking at the substrate of the microchip device, plastic and glass are generally used. However, plastics have good processability but have problems with chemical resistance. Further, glass has high chemical resistance, but its workability is inferior to that of plastic and its mechanical strength is low. Therefore, durability is somewhat difficult in view of practical application.

  From the viewpoint of the efficiency of solvent extraction, the extraction temperature is an important factor. However, as shown below, the thermal conductivity of plastic is smaller than that of glass or metal. The temperature responsiveness in the flow path is not high.

Thermal conductivity [cal / cm · s · K]
Copper 0.934
Aluminum 0.523
Stainless 0.037
Polypropylene 0.33 × 10 ^-3
Glass 0.13
In addition, metal is a material having high mechanical strength, durability, chemical resistance, and thermal conductivity, but since it is not highly workable, it is rarely used as a substrate for microchip devices.

  An object of the present invention is to provide a microchip device having a high-function liquid-liquid separation function that overcomes the problems of the prior art by making full use of high micromachining technology for metal materials such as stainless steel in view of the above points. There is.

In order to achieve this object, a microchip device according to the present invention includes:
Two kinds of liquids that do not mix with each other are introduced into one fine channel from separate channels, and are passed through the fine channel while forming a two-layer flow in contact with each other through the interface in the fine channel. Later, in the microchip device configured to again take out the two types of liquid into separate flow paths,
The fine channel is formed by forming a groove in at least one of the first plate-like member and the second plate-like member and then bonding them together, and the fine channel on the side where the hydrophilic liquid flows The inner wall is made of hydrophilic chemical treatment, and the inner wall on the side where the hydrophobic liquid flows is subjected to hydrophobic chemical treatment so that two kinds of liquid flow in a two-layer flow,
A partition member protruding so as to partition the two laminar flows from both sides along the interface between the two kinds of liquids is provided on the side wall of the fine channel.

  The plate-like member is made of metal and can be temperature-controlled.

  The hydrophobic and hydrophilic chemical treatment is characterized in that it is a method of coating a hydrophobic or hydrophilic thin film, or a method of fixing hydrophilic fine particles or hydrophobic fine particles to a flow path.

  The partition member is characterized in that a cross section is tapered.

  Further, the partition member is characterized in that the protrusion from the base portion to the interface is larger on the downstream side than on the upstream side of the fine channel.

  Further, the thickness of the partition member is 30% or less of the channel depth of the fine channel, and the width of the partition member is so that two kinds of liquids are taken out from the micro channel separately into separate channels. At the branch point, the length is at least 60% of the channel width.

  In addition, the partition member portion can be removed from the microchip device and replaced, and the position and size of the partition member overhang can be arbitrarily selected according to the flow rate of the two-layer flow. Yes.

  Further, the partition member is attached to a side wall of the fine channel by being fitted into a long groove formed along a joint portion between the two plate-like members.

According to the microchip device of the present invention,
Two kinds of liquids that do not mix with each other are introduced into one fine channel from separate channels, and are passed through the fine channel while forming a two-layer flow in contact with each other through the interface in the fine channel. Later, in the microchip device configured to again take out the two types of liquid into separate flow paths,
The fine channel is formed by forming a groove in at least one of the first plate-like member and the second plate-like member and then bonding them together, and the fine channel on the side where the hydrophilic liquid flows The inner wall is made of hydrophilic chemical treatment, and the inner wall on the side where the hydrophobic liquid flows is subjected to hydrophobic chemical treatment so that two kinds of liquid flow in a two-layer flow,
Since the partition member that protrudes so as to partition the two laminar flows from both sides along the interface between the two kinds of liquids is provided on the side wall of the fine channel,
It has become possible to provide a microchip device having a high-performance liquid-liquid separation function that overcomes the problems of the prior art by making full use of high micromachining technology for metal materials such as stainless steel.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 1 and FIG. 2 show an example of components constituting a new liquid-liquid separation microchip device according to the present invention.

  In this embodiment, two kinds of liquids that do not mix with each other are introduced into one fine flow path from separate flow paths, and a two-layer flow in contact with each other through the interface is formed in the fine flow path. It is a microchip device configured to take out two kinds of liquids again in separate flow paths after passing through the inside.

  The two metal plates 1 and 2 made of a metal such as stainless steel, copper, and aluminum having a thickness of 0.5 to 10 mm, most preferably stainless steel, extend straight along the center line of the metal plate, respectively. Or [3], the groove 3 bent into the shape of [3] is prepared, and when the groove side of the metal plate 1 is faced down and placed on the groove side of the metal plate 2, the center portions of the two grooves are vertically Together, one linear microchannel is formed, and both ends of the linear microchannel apparently branch in a Y shape.

  The groove 3 is made by wet etching or drilling. The width of the groove is 200 to 1000 μm, and the depth of the groove is 50 to 250 μm. One metal plate is subjected to hydrophobic chemical treatment on the groove surface, and the other metal plate is subjected to hydrophilic chemical treatment on the groove surface.

  Hydrophobic and hydrophilic chemical treatment methods on the groove surface include, for example, a method of coating a hydrophobic or hydrophilic thin film, a hydrophobic fine particle whose surface is modified with hydrophilic fine particles or hydrophobic functional groups such as silica gel There is a method of fixing fine particles in a flow path.

  A long groove (counterbore) 4 indicated by a dotted line along the flow direction is provided to face both side walls of the flow path of the straight fine flow path (a joint portion of the two plate-like members). It has a structure in which a piece part 5 having an edge serving as a partition plate for dividing the upper and lower flow paths in a fitting form is inserted. The contact surface of each component is all processed into a mirror surface, and is structured to prevent liquid leakage from the flow path by tightening with screws or the like up and down.

  Edge pieces are used when the flow rate of the sample solution flowing through the flow path is high, and those used when the flow rate of the sample solution flowing through the flow path is low, and can be arbitrarily selected and replaced. It can be done. The edge piece shown on the upper side of FIG. 2 is for a high flow rate, and the edge piece shown on the lower side of FIG. 2 is for a low flow rate.

  When the flow rate is high, the liquid-liquid contact time is shortened, and therefore the distance from the mixing portion to the beginning of the edge is set longer than that of the device for the slow flow rate. On the other hand, when the flow rate is slow, the liquid-liquid contact time becomes long, so the distance from the mixing portion to the beginning of the edge is set shorter than that of a device for high flow rate.

FIG. 3 shows a cross-sectional view of a microchip device incorporating an edge piece. In the cross section A, a cross section a _{1 of the} flow path into which the hydrophilic liquid is introduced and a cross section a _{2 of the} flow path into which the hydrophobic liquid is introduced appear. In the cross section B, cross sections of the edge piece parts b ₁ and b ₂ (portions where the edge does not protrude) fitted to the flow path side wall of the straight portion appear. In the cross section C, the cross sections of the edge piece parts c ₁ and c ₂ (the part where the edge protrudes to the middle) fitted to the flow path side wall of the straight part appear. The region above the edge is the region where the hydrophilic liquid flows, and the region below the edge is the region where the hydrophobic liquid flows. And both liquids contact in the vicinity of the interface which connects the front-end | tip of an edge. In the cross section D, the cross sections of the edge piece parts d ₁ and d ₂ (parts where the edges protrude greatly) fitted to the flow path side wall of the straight part appear. The distribution of the liquid is the same as in the case of the cross section C. Since section E is the same as section A, it is omitted.

  This embodiment operates as follows. First, a reagent solution (for example, an aqueous solution) and an extraction solvent (for example, ether) are separately introduced from the two inlets on the left side of FIG. The groove surface is initially set so that an aqueous solution flows on the side subjected to hydrophilic chemical treatment and ether flows on the side subjected to hydrophobic chemical treatment. Note that an eluent from a liquid chromatograph device may be directly introduced instead of the reagent solution.

  The two solutions flow from the left to the right in the fine channel, come into contact with the Y-shaped mixing part, are divided into upper and lower parts according to the chemical properties of the inner wall, and flow in a laminar flow in the straight channel. Liquid-liquid extraction is performed between the two liquid layers while the two liquids flow in a laminar flow up and down in accordance with the inner wall chemistry.

  The liquid-liquid interface is physically separated from the two laminar flows by the protrusion of the edge that has a taper-shaped cross-section that divides the micro-channel vertically from the middle of the straight micro-channel part. And separately collected in the downstream Y-shaped flow path.

  The protrusion of the edge from the base portion to the interface is larger on the downstream side than the upstream side of the linear microchannel. The edge has a maximum thickness of 30% of the channel depth, and the edge length is sized to block at least 60% of the channel width at the channel branch point.

  The present embodiment is a device design when a temperature control element 6 such as a Peltier element is incorporated in a microchip device for the purpose of controlling the liquid-liquid extraction efficiency. As shown in FIG. 5, the temperature control element 6 is disposed along both sides of the straight flow path portion that performs liquid-liquid extraction, and controls the temperature of the extraction portion to a desired temperature.

  One of the reasons for using a metal plate such as stainless steel, copper, or aluminum as the material of this microchip device is that it is highly responsive to the temperature, which is one of the factors affecting the extraction efficiency (heat conduction). This is due to a request to use a material with a high rate.

  Widely used in liquid-liquid extraction equipment.

It is a figure which shows one Example of the microchip device component concerning this invention. It is a figure which shows another Example of the microchip device component concerning this invention. It is a figure which shows sectional drawing of the microchip device concerning this invention. It is a figure which shows one Example of the microchip device concerning this invention. It is a figure which shows another Example of the microchip device concerning this invention.

Explanation of symbols

1, 2: metal plate, 3: groove, 4: long groove, 5: piece part, 6: temperature control element, a ₁ , a ₂ : flow path, b ₁ , b ₂ , c ₁ , c ₂ , d ₁ , d ₂ : Edge piece

Claims (8)

Two kinds of liquids that do not mix with each other are introduced into one fine channel from separate channels, and are passed through the fine channel while forming a two-layer flow in contact with each other through the interface in the fine channel. Later, in the microchip device configured to again take out the two types of liquid into separate flow paths,
The fine channel is formed by forming a groove in at least one of the first plate-like member and the second plate-like member and then bonding them together, and the fine channel on the side where the hydrophilic liquid flows The inner wall is made of hydrophilic chemical treatment, and the inner wall on the side where the hydrophobic liquid flows is subjected to hydrophobic chemical treatment so that two kinds of liquid flow in a two-layer flow,
A microchip device characterized in that a partition member extending so as to partition a two-layer flow from both sides along an interface between the two kinds of liquids is provided on a side wall of the fine channel. 2. The microchip device according to claim 1, wherein the plate-like member is made of metal and can be controlled in temperature. The hydrophobic and hydrophilic chemical treatment is a method of coating a hydrophobic or hydrophilic thin film, or a method of fixing hydrophilic fine particles or hydrophobic fine particles to a flow path. Microchip device. The microchip device according to claim 1, wherein the partition member has a tapered cross section. 2. The microchip device according to claim 1, wherein the partition member has an overhang from the base portion to the interface that is larger on the downstream side than on the upstream side of the fine channel. The partition member has a thickness of 30% or less of the flow path depth of the fine flow path, and the horizontal width of the partition member is a branch that separates two kinds of liquid from the fine flow path into separate flow paths. 2. The microchip device according to claim 1, wherein the microchip device has a length that covers at least 60% of the flow path width. The partition member portion is configured to be removable from the microchip device and replaceable, and the position and size of the overhang of the partition member can be arbitrarily selected according to the flow velocity of the two-layer flow. Item 2. The microchip device according to Item 1. 2. The micro of claim 1, wherein the partition member is attached to a side wall of the fine flow path by being fitted into a long groove formed along a joint portion of the two plate-like members. Chip device.

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