JP2002257838A - Drive mechanism capable of positioning and chip with the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To solve the problem that the absence of a simple drive mechanism of an integrated chemical chip in which a micro-channel, reaction, and an analyzing device are incorporated on one chip and which is capable of transferring a flowable reagent in the channel while precisely positioning the reagent and being integrated on the same chip as the channel obstructs the sophistication of the chip. SOLUTION: The devised drive device is capable of step-by-step positioning by combining a pump capable of controlling a force with the channel in which a plurality of obstructions capable of trapping a moving interface by surface tension are arranged, forming them on the same chip, and releasing the trapping by a pulsating force exceeding the force of the trapping.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The field of microfluidics and microfabrication in which microfabrication of semiconductors is applied to biochemistry, microchannels, reactions, and analyzers are built on a chip, and analysis is performed on one chip. to
tal analysis (μ-TAS), Lab-o
The field called na-chip is a DNA chip,
It shows a very rapid rise as a high-speed electrophoresis chip. Not only in the field of analysis, but also in chemical synthesis, the integration of chemistry as a mass-synthesized chip utilizing high reactivity associated with miniaturization and massive parallelism resulting from miniaturization is progressing. In addition, biochemistry is based on the technique of determining the base sequence of the human genome, analyzing the expression mechanism of proteins for the purpose of genomic drug discovery, or searching for effective components from a large number of random gene sequences. Opportunities for handling ingredients on a large scale are increasing. The present invention relates to a mechanism for transporting a substance such as a liquid on an integrated chemical chip used in such a field.

[0002]

2. Description of the Related Art Using a semiconductor fine processing technique or the like, a fine groove is dug on a quartz or resin plate, and a plate with a hole is covered to form a flow path. These flow paths are joined or branched in a pattern designed in advance, and mixing, reaction, separation, and analysis can be performed by flowing a substance therein. A phenomenon called electroosmotic flow is often used for the movement of the substance in the flow channel. An electroosmotic flow is a method in which a liquid such as an aqueous solution is placed inside a narrow flow path, and when a voltage is applied to both ends of the flow path, a force is applied to an electric double layer formed between the liquid and the wall, and the liquid moves. It is a phenomenon. In a branched or merged flow path, the flow at the branch / merge point can be controlled and the direction and flow ratio can be changed by applying an appropriate voltage to the liquid reservoir at the end of each branch / merge point. It is. In this method, all branches / confluences are electrically connected, and the voltage applied to each node is a solution of a complex system of equations, and it is necessary to prepare as many high voltage sources as the number of contacts, which increases the scale. Was blocked. In addition, since a voltage is applied to the entire flow path through which the substance to be actually conveyed flows, it becomes easily uncontrollable due to bubbles mixed in or generated in the flow path, and the electric conductivity of the substance flowing through the flow path changes with the reaction. If the flow path cross-sectional area changes due to foreign matter or solid conveyed material, an appropriate voltage for controlling the flow changes, which is very difficult to control.

[0003] The order of mixing the chemicals is determined by the order of connection of the flow paths, and thus the processing procedure is fixed at the time of chip design. In such a continuous flow process, the reaction time is determined mainly by the length of the flow path and is fixed. Some chips can perform batch-type processing in which the connected reaction layers are sequentially conveyed at an arbitrary timing when the chips are used, by air pressure applied from outside the chips or centrifugal force due to rotation. Some have a mechanical valve to control the direction of liquid flow,
This valve is also controlled by air pressure from the outside. However, these high-performance chips require large external devices, and impair the merits of chip formation such as small size and portability. There is no example of a general purpose chip that can be programmed to use the procedure.

[0004]

The difficulties and limitations as described above can be easily integrated on a chip, have a small area occupation rate, and are suitable for large-scale use, easy to use, and suitable for handling liquid. It has to do with the lack of a drive. The present invention provides an actuator that satisfies such conditions and performs a linear operation capable of precisely controlling a moving amount like a stepping motor. As a result, a chemical integrated chip or the like whose procedure can be determined at the time of use can be easily realized without using a valve.

[0005]

SUMMARY OF THE INVENTION As shown in FIG. 1, the present invention provides an integrated pump capable of controlling a force and a fixed or designed interval such as a row of dots formed in a flow path. It consists of a combination of regions where a plurality of obstacles having different shapes and surface properties are arranged. When a substance having an interface such as a liquid and a gas is fed or drawn into the area of the obstacle using a pump, the interface is trapped by the obstacle due to surface tension. Next, when a force exceeding the trapping force is applied by a pump, the trap is released, and the interface starts to move to the next obstacle. If you reduce the power of the pump to a value that cannot exceed the trap while moving, it will be trapped again at the next obstacle. That is, if appropriate conditions are set, a pulse-like force is applied by a pump to move one obstacle by one pulse,
It is possible to realize a linear actuator as if it were a stepping motor.

[0006]

FIG. 2 shows a basic type of an embodiment of the present invention. According to the present invention, the movement amount whose position is precisely controlled is transmitted by using a gas-tight medium and a gas-tight flow path that is continuous with the movement amount, and the target object is moved while being precisely positioned. As the integrated pump capable of controlling the force used in the present invention, for example, an electrode that is airtight and does not generate bubbles (such as a salt bridge using a gel such as polyacrylamide patterned by photocuring) is used. Such as a conventional electroosmotic pump. In particular, the combination with such an electroosmotic pump is promising because a scaling rule in which the capability is improved as the size is reduced is established. Also, in the present invention, unlike the conventional techniques, the pump unit, the position control unit, and the substance to be actually conveyed can be made of the same substance, but are connected by a medium capable of transmitting pressure, There is a great advantage in that it can be designed independently. For example, if a gas or a liquid that is insulative and does not mix (oil versus water) is used
The substance to be transported, the electrical connection between the pump and the position control unit and the connection where the substance is diffused and mixed can be cut off, each can be designed electrically and materially independently,
Can be optimized. FIG. 3 shows an embodiment in which a plurality of the present invention are combined. Thus, when a plurality of the present invention are combined,
The advantage that each can be designed independently is further emphasized. For the sake of simplicity, it is assumed below that the pump and the actuating material of the positioning mechanism, the aqueous solution as the transport material and the air as the pressure medium between them. That is, in the continuous flow type chip using the electroosmotic flow as described in the related art, since all the junctions / junctions are electrically connected, the voltage is prepared by the number of the contacts. And refused to scale up. In the present invention, since the insulation is provided electrically, the scale can be easily increased simply by juxtaposition. Further, when the advantage that the material continuity can be cut by a pressure medium such as a gas and the advantage that it can be precisely positioned are combined, the following advantages are obtained. That is, by precisely controlling the positions of a plurality of flowing substances separated by the pressure medium in the flow path, the plurality of substances can be moved to an arbitrary position without using a valve so as not to be mixed with each other. It is easily possible to separate two liquid masses into a plurality of liquid masses or to mix them as necessary, using the configuration of FIG. Therefore, by using the configuration of FIG. 3, it is possible to easily realize that the chemical solution is taken out of the reservoir in an arbitrary order as needed, guided to the reaction layer in an arbitrary order and reacted, and analyzed in the analysis layer as needed. It is. That is, a general-purpose chemical chip can be realized in which the processing procedure can be determined when the chip is used, and various programs can be realized on a case-by-case basis by assembling various programs when the chip is used. This is a great merit compared to a conventional chip in which the processing procedure is determined and fixed at the time of chip design.

[0007]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment in which the present invention is implemented on a chip made of quartz will be described below. 20mm × 2
A 1 μm thick Cr film is sputtered on a 0 mm quartz plate and patterned by photolithography and wet etching. Using this as a hard mask, C ₄ F ₈ + CH ₂ F ₂
30 μm width, 20 depth by MLD plasma using gas
A μm channel is formed. A quartz lid having an inlet / outlet was press-bonded in 1% HF to form a chip. An electroosmotic flow using a gel salt bridge electrode patterned by applying a solution containing acrylamide, bisacrylamide, and a photo-curing initiator into the flow channel and applying ultraviolet light only to the salt bridge, and using it as an airtight and bubble-free electrode A pump was formed. Cylinders with a diameter of 5 μm were erected at intervals of 100 μm without a flow path to serve as obstacles. This was diluted with a physiological phosphate buffer solution to 1/10 and introduced from a pump section to obtain a working fluid. This working fluid flows to the position control unit, and the interface between the gas and the liquid is trapped in a cylinder by surface tension to realize a stepping operation. The pump used can generate a fixed pressure in proportion to the applied voltage. As shown in FIG. 4, forward and backward stepping operations were confirmed by changing the pressure in a pulsed manner.

[0008]

According to the present invention, an actuator which can be easily integrated on a chip, has a small occupied area, is suitable for large-scale operation, and has a linear operation capable of precisely controlling a moving amount like a stepping motor is realized. did it. Further, by using such an actuator, the positions of a plurality of liquids in a flow path are precisely controlled, so that the plurality of liquids can be moved to an arbitrary position without using a valve so as not to mix with each other. It is also possible to separate two liquid masses into a plurality or to mix them as needed.
A general-purpose chip whose processing procedure can be programmed at the time of use can also be realized.

[Brief description of the drawings]

FIG. 1 is a diagram illustrating a principle for performing a positioning operation according to the present invention.

FIG. 2 is a view showing an embodiment in which one of the present invention is combined with an electro-osmotic flow pump to realize precise positioning of a remote droplet using a gas as a medium.

FIG. 3 is an embodiment of a case where the present invention is applied to a large-scale general-purpose chemical chip in which a plurality of the present invention are used and a processing procedure can be programmed at the time of use.

FIG. 4 is a diagram showing a stepping operation confirmed and realized by realizing the present invention on a chip using quartz.

[Explanation of symbols]

1 Integrated pump with controllable force 2 Flow path 3 Obstacle trapping interface by surface tension 4 Working substance A (liquid etc.) 5 Working substance B (gas etc.) 6 Interface between working substances A and B 7 Pulse voltage Input 8 Platinum electrode 9 Gel salt bridge electrode 10 Pump unit 11 Phosphate buffer 12 Pressure medium (air) 13 Substance to be conveyed (reagent etc.) 14 Obstacle trapped at the interface by surface tension composed of cylinders 15 Liquid reservoir 16 Common Channel 17 Actuator composed of pump and positioning device (the present invention) 18 Reaction layer etc. 19 Analysis layer etc. 20 Heater etc. 21 Reservoir of chemical liquid

Claims (4)

[The claims] 1. A driving device for forming a flow path inside a chip and transporting a substance in the flow path while positioning the flow path. A plurality of obstacles with different roads and shapes or surface properties are placed, and the interface of the material flowing through them is trapped by the obstacles due to surface tension, and the trap is removed with a pulse-like force exceeding the trapping force. A positioning mechanism characterized by stepwise positioning by moving to an object and being trapped there again. 2. The same chip as the positioning mechanism according to claim 1, a driving device for generating a force such as an electroosmotic flow pump using a gel electrode on one side, and a flow path through which a substance to be actually conveyed passes. In the pump, the positioning mechanism, and the actual mass transfer, the force acting between them is transmitted through the flow path by the same or different gas or liquid as the substance to be actually conveyed, and the target substance transfer is achieved. A chemical integrated chip characterized in that electrical connection between transported substances or physical connection such as mixing due to diffusion of a substance is divided as necessary to facilitate design. 3. A flow path provided with a stepwise positioning mechanism according to claim 1, a branch point is provided at a position where the flow path can be positioned, and a reagent storage, various reaction devices, an analysis device, etc. By disposing materials in any order between them, it is possible to perform mixing, reaction, analysis, etc. of substances not only in the procedure determined at the time of chip design but also in any procedure when using the chip. Characterized chemical integrated chip. 4. The use of a valve by precisely controlling the positions of a plurality of flowing substances in a flow path using a flow path in which the step-like positioning mechanism according to claim 1 is integrated on the same chip. A chemical integrated chip characterized by moving a plurality of substances to an arbitrary position so as not to mix with each other, or separating one liquid mass into a plurality of liquid masses, or mixing them as necessary.