WO2003076038A1

WO2003076038A1 - Method of enriching liquid phase inside micro chip by gas-liquid two-phase flow and micro chip device therefor

Info

Publication number: WO2003076038A1
Application number: PCT/JP2003/002337
Authority: WO
Inventors: Takehiko Kitamori; Manabu Tokeshi; Akihide Hibara
Original assignee: Kanagawa Academy Of Science And Technology
Priority date: 2002-03-14
Filing date: 2003-02-28
Publication date: 2003-09-18
Also published as: JP4424993B2; JPWO2003076038A1

Abstract

A method of enriching liquid phase inside a micro chip having a flow passage formed in the substrate thereof, comprising the steps of forming a boundary face in the flow passage by a gas-liquid two phase flow for enriching the liquid phase, wherein an enriching method followed by a volumetric change is integrated in the micro chip, whereby the liquid phase can be enriched at a high efficiency.

Description

Description Method of concentration in microchip by gas-liquid two-phase flow and

Microchip devices for that purpose

The invention of this application relates to a method for concentration in a microchip by a gas-liquid two-phase flow and a microchip device therefor. Background art

In recent years, studies on microchemical systems that take advantage of the characteristics of microspaces have been advanced in various fields. The inventors of this application have already established a method called a continuous fluid chemical process that combines micro-unit operation and a multi-phase flow network as a method to realize a complex chemical system. This continuous fluid chemistry process is characterized by the ability to construct a very efficient microphone-mouth chemistry system by combining multiple micro-unit operations such as mixing / extraction and phase separation. However, in conventional microsystems, the concentration of the process was set to a parameter, and the concept of volume change was not included. For this reason, the concentration method with volume change and the condensation method have not been realized.

Thus, the invention of this application has an object to integrate a concentration method involving a volume change as an operation on a microchip, based on the development of a microchemical system by the inventors and their knowledge so far.

More specifically, it is an object of the invention of the present application to provide a new concentration method using evaporation of a solvent in a gas-liquid two-layer flow in a channel of a microchip, and a microchip device therefor. Disclosure of the invention

The invention of this application solves the above problems. First, in a microchip having a flow path formed in a substrate, a liquid-phase two-phase flow is formed in the flow path to form a liquid-phase interface. Provided is a method for concentrating in a microphone-mouth chip by gas-liquid two-phase flow, which is characterized by performing concentration.

Secondly, the invention of this application is characterized in that the above-mentioned enrichment method is characterized in that the flow rate ratio between the gas phase and the liquid phase in the flow path is controlled so that gas phase> liquid phase. The fourth is a condensing method characterized by forming a gas-liquid interface in multiple stages by introducing gas into the flow path in multiple stages and discharging the gas. Fourth, a gas-liquid two-phase flow is used. Provided is a concentration method characterized by heating at least a part of a formed flow path to evaporate a part of a liquid phase solvent.

Fifth, the invention of this application is a device for concentrating a liquid phase by forming an interface by a gas-liquid two-phase flow in a flow channel in a microchip having a flow channel formed in a substrate. Thus, a microchip device is provided, in which a gas and a liquid constituting a gas-liquid two-phase flow are respectively provided with an introduction path and a discharge path.

Sixth, the above-mentioned microchip device is characterized in that a flow rate control mechanism for controlling the flow rate ratio in the flow path to be gas phase> liquid phase is provided. On the bottom of the flow channel, there is provided a ridge in the flow direction corresponding to the position of the gas-liquid interface, and the arrangement of the ridge is at least part of the flow control mechanism. Eighth, a micro flow path is provided in which a gas is introduced into the flow path in multiple stages to form a gas-liquid interface in the flow path in multiple stages, and the gas is discharged in accordance with the multi-stage flow. The ninth is a microchip device characterized in that a heating mechanism for heating at least a part of a flow path in which a gas-liquid two-phase flow is formed is provided. In the case of 0, heat is applied to the back of the substrate on which the flow path is provided or to the surface of the upper plate. The present invention provides a microchip device characterized in that a heater or a planar heater is provided.

1 BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic diagram showing the basic configuration of the invention of this application.

FIG. 2 is a cross-sectional view showing an example of an asymmetric microchannel having a ridge.

FIG. 3 is a schematic process diagram illustrating a method for forming a fine channel having a ridge. FIG. 4 is a schematic process diagram illustrating a two-step etching method for forming an asymmetric fine channel.

Fig. 5 is a schematic diagram illustrating the arrangement of the Hi-Ichi Line.

FIG. 6 is a schematic process diagram illustrating a method for forming a line of heaters.

FIG. 7 is a schematic cross-sectional view of an asymmetric fine channel as an example.

FIG. 8 is a schematic perspective view of a microchip as an embodiment provided with a microheater.

FIG. 9 is a diagram illustrating the relationship between the concentration and the applied voltage in the example. <FIG. 10 is a schematic diagram of a three-stage channel.

FIG. 11 is a diagram exemplifying a stable condition of a two-phase flow of ethyl acetate and air.

FIG. 12 is a diagram illustrating a stable condition of a two-phase flow of water and air. In addition, the code | symbol in a figure shows the following.

1 Microchip substrate

2 Micro channel

3 A gas phase

3 B liquid phase

4 A gas inlet

4 B liquid introduction path

5 A gas discharge path

5 B liquid discharge path

6 ridge

7 Heater wire BEST MODE FOR CARRYING OUT THE INVENTION

The invention of this application has the features as described above, and embodiments thereof will be described below.

First, in the enrichment method of the invention of this application, an interface is formed by a gas-liquid two-phase flow of gas and liquid in a fine channel (microchannel) formed on a substrate of a microchip to concentrate the liquid phase. It is fundamental to do.

This enrichment method is an enrichment operation in a small, limited space called a microchannel, which has a large specific interfacial area, a high evaporation rate of the solvent, and is performed under the restriction of gas-liquid equilibrium. It has a fundamental feature that control is easy because it is maintained.

FIG. 1 is a schematic diagram showing the basics of the enrichment method of the invention of this application. For example, a microchannel (2) formed by microfabrication such as etching is provided on a microchip substrate (1) made of glass, ceramics, silicon, resin, or the like. In the fine channel (2), a gas-liquid two-phase flow of a gas phase (3A) and a liquid phase (3B) is formed, and a solvent constituting the liquid phase (3B) is formed at the interface (3C). It is evaporated and concentrated. Of course, on the substrate (1) on which the fine channels (2) are formed, the cover upper plate is placed in close contact to prevent the gas phase (3A) from dissipating the liquid phase (3B). . The gas introduction path (4 A) and the liquid introduction path (4 B) for forming the gas-liquid two-phase flow, and the gas discharge path (5A) and the liquid discharge path (5 B) are the same. It is arranged on the substrate (1) by fine processing.

The size and length of the microchannel (2) are not particularly limited, but are appropriately set for configuring a microchemical system on a microchip. For example, looking at a cross section orthogonal to the flow direction of the microchannel, a practical guideline is that the width is 500 / xm or less and the depth is about 300 im or less.

And in the enrichment method of the invention of this application, the fine channel Since it is necessary to form an interface due to gas-liquid two-phase flow in the channel, the cross-sectional area of the microchannel and the types of substances constituting each of the gas phase and the liquid phase are taken into consideration. A suitable gas-phase and liquid-phase flow ratio for interface formation will be set.

In general, the flow rate ratio between the gas phase (3A) and the liquid phase (3B) in the microchannel (2) is set so that the flow rate of the gas phase is larger than the flow rate of the liquid phase. It is desirable to control. However, if the flow rate of the gas phase is excessive or excessive with respect to the flow rate of the liquid phase, liquid phase substances are mixed in the gas phase, and an interface as a gas-liquid two-phase flow is not formed. Of course, conversely, even when the gas flow rate is too small, the formation of the interface becomes difficult.

However, in general, as described above, it is preferable that the flow rate ratio between the gas phase and the liquid phase is gas phase> liquid phase. It is also considered that the microchip is provided with a mechanism as an auxiliary means for controlling the flow ratio with high accuracy. For example, as one of such control mechanisms, a ridge (6) in the flow direction corresponding to the position of the gas-liquid interface is provided at the bottom of the microchannel (2), as shown in the cross-section in Fig. 2. It is considered that the flow rate ratio between the gas phase (3A) and the liquid phase (3B) can be controlled by selecting the location of the ridge (6).

Of course, the ridge (6) plays the role of a guide, and not only when it is strictly located at the gas-liquid interface (3C), but also a gas-liquid two-phase flow and a predetermined flow rate ratio are ensured. It goes without saying that, under the condition, there may be a deviation from the gas-liquid interface (3 C) position at an allowable position as shown in FIG.

Depending on the position of the ridge (6), a microchannel (2) having an asymmetrical cross section, as shown in the example of Fig. 2, is one of the effective means for increasing the gas flow rate.

As for the formation of the microchannel (2) and the ridge (6), for example, as shown in Fig. 3, a photoresist is disposed on a metal deposition film on the surface of a glass substrate, and UV light is irradiated through a mask. Transfer and then metal etching ゃ hydrofluoric acid etching and development ぅ photolithography and etching

Five

Clear ffl paper (Rule 9 Can be formed. According to this method, as shown in Fig. 4, by performing two-stage etching in which transfer and etching are repeated, an asymmetric fine channel (2) having ridges (6) as shown in Fig. 2 can be formed. it can.

In the invention of this application, it is also effective to heat at least a part of the gas-liquid two-phase flow to generate a part of the liquid phase solvent by this heating. Various mechanisms can be considered for such a heating mechanism. However, from the viewpoint of the device configuration and the heating operability, the back surface or the cover of the substrate provided with the fine flow path is considered.

-It is exemplified that it is preferable to provide a line heater or a plane heater by resistance heating on the surface of the upper plate or the like. FIG. 5 shows an example in which such a heater line (7) is provided. For example, as shown in FIG. 6, it can be easily formed by etching a Cr vapor deposition film.

Further, with respect to the concentration method of the invention of the present application and a device therefor, for example, a plurality of interfaces by gas-liquid two-phase flow as described above may be provided intermittently so that concentration operation can be performed in multiple stages. For this purpose, it is considered to provide multiple gas flow paths for introducing and discharging the gas at each stage.

For example, the invention of the present application as described above enables highly efficient concentration operation on a microchip.

Therefore, an embodiment will be shown below and will be described in more detail. Of course, the invention is not limited by the following examples. Example

As shown in Fig. 1, a Co-DMAP complex in ethyl acetate was introduced from one of the double Y-type microchannels, and air was introduced from the other inlet to create a gas-liquid two-layer structure in the microchannel. A flow is formed, and the organic phase is measured along a microchannel with a thermal lens microscope, and concentrated as a change in the concentration of Co-DMAP complex per unit volume based on the relationship between the measurement position of the thermal lens microscope and the signal intensity. The efficiency was evaluated. And increase the concentration efficiency from the viewpoint of vapor-liquid equilibrium. For this purpose, a chip with asymmetric microchannel cross section (Fig. 7) was used. In addition, a micro-hidden was prepared on the back of the microchip and concentrated by heating.

That is, first, an asymmetric microchannel having the cross section shown in FIG. 7 was prepared by using the two-step etching method illustrated in FIG. 4, and the flow rate ratio was set to 1: 200 using this channel to perform measurement. In this case, a concentration of about 2 times was obtained, and evaporation in the microchip was confirmed. Furthermore, in order to increase the concentration efficiency, a micro-heater was fabricated by patterning a Cr thin film on the back surface of the microchip by etching as shown in Fig. 6 (Fig. 8), and the chip was locally heated. Fig. 9 shows the results of concentration measurement at a point of 30 mm after two-phase merging using this chip. The heat lens signal intensity increases with an increase in applied voltage, that is, a rise in temperature, indicating that the enrichment is improved by heating. From the signal intensity, the enrichment was more than 4 times (75% of the solvent evaporated) by volume change.

Assuming that a four-fold concentration can be obtained at a flow rate of 1: 20000, a three-stage operation as illustrated in FIG. 10 will actually achieve a 64-fold concentration rate.

In order to determine the stable conditions for the formation of an interface by gas-liquid two-phase flow, the above microchip was experimentally examined by changing the combination of gas and liquid phases and the flow rate ratio. The results are illustrated in FIGS. 11 and 12.

Fig. 11 shows the case of air and ethyl acetate, Fig. 12 shows the case of air and water, and region A in the figure shows the stable condition, and region B shows the unstable condition due to excess air. The C region indicates that the liquid is excessive and unstable.

For example, based on such studies, suitable stable flow rate ratio conditions will be specifically determined for various types of enrichment targets. Industrial applicability

As described in detail above, the invention of this application involves volume change

7 The enrichment method can be integrated on a microchip, and highly efficient enrichment can be achieved. This is very useful for the detection, measurement, and separation / recovery of environmentally regulated substances in the liquid phase, biologically related substances, biological substances, and trace substances such as reaction intermediates and reagents. Concentration on a microchip becomes possible.

Claims

The scope of the claims

1. Concentration in a microchip with gas-liquid two-phase flow characterized by forming an interface by gas-liquid two-phase flow in the flow channel and concentrating the liquid phase in a microchip with a flow path formed in the substrate Method.

2. The enrichment method according to claim 1, wherein the flow rate ratio between the gas phase and the liquid phase in the flow path is controlled so as to be gas phase> liquid phase.

3. The method according to claim 1, wherein a gas-liquid interface is formed in multiple stages by introducing gas into the flow channel in multiple stages and discharging the gas in the multiple stages.

4. The method according to any one of claims 1 to 3, wherein at least a part of the flow path in which the gas-liquid two-phase flow is formed is heated to evaporate a part of the liquid phase solvent.

5. A device for concentrating a liquid phase by forming an interface by a gas-liquid two-phase flow in a flow channel in a microchip having a flow channel formed on a substrate. A microchip device characterized in that a liquid introduction path and a liquid discharge path are provided.

6. The microchip device according to claim 5, wherein a flow rate control mechanism for controlling a flow rate ratio in the flow path to be a gas phase> a liquid phase is provided.

7. The flow path according to claim 6, wherein a protrusion in the flow direction corresponding to the gas-liquid interface position is provided at the bottom of the flow path, and the arrangement of the protrusion is at least a part of the flow control mechanism. Microchip device.

8. A flow path for introducing gas into the flow path in multiple steps and discharging the gas in the flow path for forming a gas-liquid interface in multiple steps in the flow path is provided. Any of Microchip Devis.

9. The microphone chip device according to any one of claims 5 to 8, further comprising a heating mechanism for heating at least a part of the flow path in which the gas-liquid two-phase flow is formed.

10. The microchip device according to claim 9, wherein a heater wire or a planar heater is provided on a back surface portion of the substrate provided with the flow path or on a surface portion of the upper surface of the force plate.