JP4424993B2 - Microchip concentration method in gas-liquid two-phase flow and microchip device therefor - Google Patents

Description

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

  In recent years, studies on microchemical systems that make use of the characteristics of microspaces have been promoted in various fields. The inventors of this application have already established a method called a continuous fluid chemical process combining a micro unit operation and a multiphase flow network as a method for realizing a complex chemical system. This continuous fluid chemical process has a feature that a very high-efficiency microchemical system can be constructed by combining a plurality of micro unit operations such as mixing, extraction, and phase separation. However, in the conventional microsystem, the process is set with the concentration as a parameter, and the concept of volume change has not been included. Therefore, the concentration method and the condensation method with volume change have not been realized.

  Therefore, the invention of this application is based on the development of a microchemical system by the inventors and the knowledge therefor, and an object is to integrate a concentration method with volume change as an operation on a microchip.

  More specifically, an object of the invention of this application is 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.

  In order to solve the above problems, the invention of this application is as follows. First, in a microchip in which a channel is formed on a substrate, an interface by a gas-liquid two-phase flow is formed in the channel to concentrate the liquid phase. A method for concentrating in a microchip with a gas-liquid two-phase flow is provided.

According to the invention of this application, secondly, the above-described concentration 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 the gas phase> the liquid phase. Is a concentration method characterized in that gas is introduced into and discharged from the flow path in multiple stages to form gas-liquid interfaces in the flow path, and fourth, a gas-liquid two-phase flow is formed. There is provided a concentration method characterized in that at least a part of the flow path is heated to evaporate a part of the liquid phase solvent.

The fifth aspect of the present invention is a device for concentrating a liquid phase by forming an interface by a gas-liquid two-phase flow in a channel in a microchip having a channel formed in a substrate, The gas-liquid two-phase flow gas and liquid introduction paths and discharge paths are arranged , and the gas-liquid two-phase flow gas phase and liquid phase area in the cross-section of the flow path are arranged at the bottom of the flow path. to regulate the ratio, the flow direction of the ridge are provided corresponding to the gas-liquid interface position, the arrangement of the ridges is characterized that you control the flow rate ratio of the gas phase and the liquid phase of the gas-liquid two-phase flow A microchip device is provided.

Sixth, the above-mentioned microchip device is characterized in that the protrusions are arranged so that the flow rate ratio in the flow channel is gas phase> liquid phase, and seventh, the gas-liquid two-phase provided introduction passage of the gas in the flow and the discharge path is in multiple stages, the microchip device gas-liquid interface in the passage is characterized in that it is a multi-stage form, the eighth, the gas-liquid two-phase A microchip device is provided with a heating mechanism for heating at least a part of a flow path in which a flow is formed . Ninth, a back surface portion or a cover of a substrate provided with a flow path the microchip device, wherein a heater wire or a planar heater is disposed on the surface portion of the upper plate to provide.

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 fine channel having protrusions. FIG. 3 is a process outline diagram illustrating a method for forming a fine flow path having protrusions. FIG. 4 is a process outline diagram illustrating a two-stage etching method for forming an asymmetric fine channel. FIG. 5 is a schematic view illustrating the arrangement of heater wires. FIG. 6 is a process outline diagram illustrating a method for forming a heater wire. 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 in which a microheater is provided. 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 illustrating the stable condition of the two-phase flow of ethyl acetate and air. FIG. 12 is a diagram illustrating the stability condition of the two-phase flow of water and air.

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

First, in the concentration method of the invention of this application, the liquid phase is concentrated by forming an interface by a gas-liquid two-phase flow of gas and liquid in a microchannel formed on the substrate of the microchip. It is basically done.
This concentration method is a concentration operation in a minute limited space called a microchannel. The specific interface area is large, the evaporation rate of the solvent is high, and it is performed under the limitation of gas-liquid equilibrium, and it is maintained as a liquid. Therefore, it has the principle feature that it is easy to control.

  FIG. 1 is a schematic diagram showing the basics of the concentration method of the invention of this application. For example, on a microchip substrate (1) made of glass, ceramics, silicon, resin, or the like, a fine channel (2) formed by fine processing such as etching is provided. In this fine channel (2), a gas-liquid two-phase flow of the gas phase (3A) and the liquid phase (3B) is formed, and the solvent constituting the liquid phase (3B) is evaporated at the interface (3C). Concentration is performed. Of course, on the substrate (1) on which the fine channel (2) is formed, the cover upper plate is disposed in close contact so that the gas phase (3A) does not dissipate the liquid phase (3B).

  The gas introduction path (4A) and the liquid introduction path (4B), and the gas discharge path (5A) and the liquid discharge path (5B) for forming the gas-liquid two-phase flow are similarly finely processed. Is disposed on the substrate (1).

  The size and length of the microchannel (2) are not particularly limited, but are set appropriately for configuring a microchemical system on a microchip. For example, when looking at a cross section perpendicular to the flow direction of the fine channel, a practical standard can be a width of 500 μm or less and a depth of about 300 μm or less.

  In the concentration method of the invention of this application, it is necessary to form an interface by a gas-liquid two-phase flow in the microchannel (microchannel). In consideration of the types of substances constituting each of the phases, a suitable gas phase and liquid phase flow rate ratio for setting the interface is set.

  Generally, the flow rate ratio per unit time between the gas phase (3A) and the liquid phase (3B) in the fine channel (2) is controlled so that the gas phase flow rate is larger than the liquid phase flow rate. It is desirable. However, if the gas phase flow rate is excessive or excessive with respect to the liquid phase flow rate, the liquid phase substance is mixed in the gas phase, and an interface as a gas-liquid two-phase flow is not formed. Of course, conversely, the formation of the interface is difficult even when the gas phase flow rate is too low.

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. The microchip is provided with a mechanism as an auxiliary means for performing such flow rate ratio control with high accuracy . And a controller configured like this, as illustrated the cross-section in FIG. 2, the bottom of the micro channel (2), provided in the flow direction ridges (6) which corresponds to the interface position of the gas-liquid The flow rate ratio between the gas phase (3A) and the liquid phase (3B) can be controlled by selecting the arrangement position of the protrusion (6) .

  Of course, the ridge (6) serves as a guide, and not only when it is strictly at the gas-liquid interface (3C) position, but also ensures that the gas-liquid two-phase flow and a predetermined flow rate ratio are ensured. Needless to say, the condition may be shifted from the gas-liquid interface (3C) position at an allowable position as shown in FIG.

  By selecting the position of the ridge (6), the fine channel (2) having an asymmetric cross section, for example, as shown in the example of FIG. 2, is one of effective means for increasing the gas flow rate.

  For the formation of the fine channel (2) and the protrusion (6), for example, as shown in FIG. 3, a photoresist is disposed on a metal vapor deposition film on the surface of the glass substrate, and UV light is irradiated through the mask. It can be formed by photolithography and etching in which transfer is performed and then development is performed by metal etching or hydrofluoric acid etching. In accordance with this method, as shown in FIG. 4, by performing two-stage etching that repeats transfer and etching, an asymmetric fine channel (2) having a protrusion (6) as shown in FIG. 2 can be formed. .

  In the invention of this application, it is also effective to heat at least part of the gas-liquid two-phase flow to generate part of the liquid-phase solvent by this heating. Various mechanisms are considered for such heating, but from the viewpoint of device configuration and heating operability, the back surface portion of the substrate provided with the fine flow path or the surface portion of the cover upper plate, It is illustrated as a suitable thing to provide the heater wire and planar heater by resistance heating. FIG. 5 shows an example in which such a heater wire (7) is provided. For example, as shown in FIG. 6, it can be easily formed by etching a Cr vapor deposition film.

Furthermore, with regard to the concentration method and the device therefor according to the invention of this application, for example, a plurality of interfaces by gas-liquid two-phase flow as described above may be provided intermittently so that the concentration operation can be performed in multiple stages. For this purpose, the gas flow path for the introduction and emissions of gases at each stage can be provided a plurality of locations are considered.

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

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

  An ethyl acetate solution of a Co-DMAP complex is introduced from one of the double Y-type microchannels as illustrated in FIG. 1, and air is introduced from the other inlet to form a gas-liquid two-layer flow in the microchannel. The organic phase was measured with a thermal lens microscope along the microchannel, and the concentration efficiency was evaluated as a change in the concentration of the Co-DMAP complex per unit volume from the relationship between the measurement position of the thermal lens microscope and the signal intensity. In order to increase the concentration efficiency from the viewpoint of gas-liquid equilibrium, a chip (FIG. 7) having an asymmetric cross section of the microchannel was used. Further, a microheater was prepared on the back surface of the microchip and concentrated by heating.

  That is, first, when a two-step etching method illustrated in FIG. 4 is used to produce an asymmetrical microchannel having the cross section of FIG. 7 and measurement is performed using this channel at a flow rate ratio of 1: 2000, 2 About twice the concentration was obtained, and evaporation within the microchip was confirmed. Further, in order to increase the concentration efficiency, a Cr thin film was patterned on the back surface of the microchip by etching as shown in FIG. 6 to produce a microheater (FIG. 8), and the chip was locally heated. FIG. 9 shows the result of concentration measurement at a point of 30 mm after two-phase joining using this chip. As the applied voltage increases, that is, the thermal lens signal intensity increases with increasing temperature, it can be seen that the degree of concentration is improved by heating. From the signal intensity, a degree of enrichment of 4 times (75% of the solvent evaporated) was obtained by the volume change.

  Assuming that a 4-fold concentration is obtained at a flow rate ratio of 1: 2000, the operation in the three stages as illustrated in FIG. 10 will actually achieve a 64-fold concentration rate.

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

  FIG. 11 shows the case of air and ethyl acetate, and FIG. 12 shows the case of air and water. In FIG. 11, the A region shows the stable condition, the B region is unstable due to excess air, and the C region. Indicates that liquid is unstable and unstable.

  For example, based on such examination, suitable stable flow rate ratio conditions are specifically determined for various types of concentration objects.

  As described above in detail, according to the invention of this application, it is possible to integrate a concentration method with a volume change on a microchip, thereby realizing high-efficiency concentration. As a result, the microchip is extremely useful for detection, measurement, separation and recovery of environmentally regulated substances in the liquid phase, biological substances, biological substances, and trace substances such as reaction intermediates and reactants. Concentration with can be performed.

DESCRIPTION OF SYMBOLS 1 Microchip board | substrate 2 Fine flow path 3A Gas phase 3B Liquid phase 4A Gas introduction path 4B Liquid introduction path 5A Gas discharge path 5B Liquid discharge path 6 Projection 7 Heater wire

Claims (9)

A method for concentrating a microchip in a gas-liquid two-phase flow, characterized in that in a microchip in which a channel is formed on a substrate, an interface is formed in the channel by a gas-liquid two-phase flow to concentrate the liquid phase. 2. The concentration 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 that the gas phase> the liquid phase. 3. The concentration method according to claim 1 , wherein the gas-liquid interface is formed in multiple stages in the flow path by introducing and discharging the gas into the flow path in multiple stages .   The concentration 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. A device for condensing a liquid phase by forming an interface by a gas-liquid two-phase flow in the channel in a microchip in which a channel is formed on a substrate, the gas and liquid constituting the gas-liquid two-phase flow Each introduction path and discharge path are disposed, and the flow path bottom corresponds to a gas-liquid interface position that regulates the area ratio between the gas phase and the liquid phase of the gas-liquid two-phase flow in the cross section of the flow path. the flow direction of the ridge are provided, the microchip device arrangement of the ridges is characterized that you control the flow rate ratio of the gas phase and the liquid phase of the gas-liquid two-phase flow. 6. The microchip device according to claim 5, wherein the protrusions are arranged so that the flow rate ratio in the flow channel is gas phase> liquid phase. The microchip according to claim 5 or 6, wherein a gas introduction path and a discharge path constituting a gas-liquid two-phase flow are provided in multiple stages, and gas-liquid interfaces are formed in multiple stages in the flow path. device. 8. The microchip device according to claim 5, 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 . 9. The microchip device according to claim 8, wherein a heater wire or a planar heater is disposed on the back surface portion of the substrate provided with the flow path or the surface portion of the cover upper plate .

Images