JP2006026791A - Micro-fluid chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a micro-fluid chip capable of making a fluid control element such as a micro-pump reusable. <P>SOLUTION: The micro-fluid chip is composed of one or more ports, a substrate having a minute flow path to communicate with the ports, and an opposite substrate which is stuck to a minute flow path forming face of the substrate. The micro-fluid chip is characterized by having a micro-fluid component assembly which is attachably/detachably self-sucked by being laid on the upper face of at least one port out of the ports or attachably/detachably self-sucked by being inserted into the port. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a microfluidic chip. More specifically, the present invention relates to a microfluidic chip in which a fluid control element such as a micropump can be detachably disposed.

  Microstructures such as microchannels, reaction vessels, and ports have been built into the substrate as is known recently under the name of Microscale Total Analysis Systems (μTAS) or Lab-on-Chip (Lab-on-Chip). A microdevice configured to perform various operations such as chemical reaction, synthesis, purification, extraction, generation and / or analysis of a substance within the microstructure has been proposed and partially put into practical use. Structures manufactured for this purpose and having a microstructure such as microchannels, ports and reaction vessels in the substrate are collectively referred to as “microfluidic chips” or simply “microchips”. Microfluidic chips can be used in a wide range of applications such as chemical industry and environmental measurement as well as chemical, biochemical, pharmaceutical, medical, and veterinary fields such as genetic analysis, clinical diagnosis, and drug screening. Compared with the same type of equipment of the common size, the microfluidic chip (1) uses significantly less sample and reagent, (2) analysis time is short, (3) high sensitivity, (4) portable to the field, It has the advantages of being able to analyze on the spot and (5) disposable.

  The material, structure and manufacturing method of the microfluidic chip are disclosed in, for example, Patent Document 1 and Patent Document 2. As described in Patent Document 1 and Patent Document 2, in general, these microfluidic chips include a substrate having a microstructure such as a microchannel (microchannel) on one plane, and these microfluidic chips. It has a structure in which a facing substrate having a target plane for sealing the structure is bonded. Various materials are used for each substrate depending on the manufacturing method, the intended use of the microfluidic chip, etc., but silicon rubber-based polydimethylsiloxane (PDMS) is used as the substrate material, and a glass substrate is used as the facing substrate. Since the PDMS substrate and the glass facing substrate are permanently bonded, there is an advantage that leakage of fluid from the microchannel or the like is completely prevented.

  A microchannel or reaction vessel in a microfluidic chip handles a fluid (mainly a liquid such as a chemical solution or a sample). For this purpose, a function for controlling the flow and transfer of the fluid is required. In particular, a small functional component built in a microfluidic chip is called a fluid control element. A typical fluid control element is a microvalve or a micropump.

  An example of a micropump disposed in a microfluidic chip is described in Patent Document 3. According to FIG. 1 of Patent Document 1, the micropump 100 includes a first channel 115 in which the channel resistance changes according to the differential pressure, and the ratio of the change in the channel resistance to the change in the differential pressure is the first channel. A second flow path 117 smaller than 115, a pressurizing chamber 109 connected to the first flow path 115 and the second flow path 117, and a piezoelectric element 107 for changing the pressure inside the pressurizing chamber 109. In addition, by changing the pressure inside the pressurizing chamber 109 with the piezoelectric element 107, the ratio of the channel resistance of the first channel 115 and the channel resistance of the second channel 117 can be made different. Thereby, a very small amount of liquid can be conveyed with high accuracy in both forward and reverse directions. However, this micropump has the following drawbacks. (1) Expensive piezoelectric elements are discarded along with the microfluidic chip, resulting in an increase in cost; (2) Drive control of the piezoelectric elements is not easy and cannot transport liquids as expected; (3) Use piezoelectric elements Therefore, the microfluidic chip cannot be reduced in size; (4) Since no on-off valves or check valves are provided before and after the pressurizing chamber, the flow of liquid cannot be completely stopped; (5) Pressurizing chamber Since there is no open / close valve or check valve before and after the pump, pump operation cannot be performed against a large external pressure; and (6) liquid flow because of the difference in flow resistance. It can be used for control but not for gas flow control.

JP 2000-27813 A JP 2001-157855 A JP 2001-322099 A

  Accordingly, an object of the present invention is to provide a microfluidic chip that allows a fluid control element such as a micropump to be reused.

  The invention according to claim 1 as means for solving the above-mentioned problems is that the one or more ports, a substrate having a fine flow path communicating with the port, and a facing surface bonded to the fine flow path forming surface of the substrate In a microfluidic chip comprising a substrate, it is placed on the upper surface of at least one of the ports and is detachably self-adsorbed, or inserted into the port and detachably self-adsorbed. A microfluidic chip having a microfluidic component assembly.

  According to a second aspect of the present invention, the substrate is made of polydimethylsiloxane, and the outer shell or the body of the microfluidic component assembly is made of polydimethylsiloxane or glass. 2. The microfluidic chip according to claim 1, wherein a part is built in the outer shell or the main body.

  The invention of claim 3 as means for solving the problem is the microfluidic chip according to claim 1 or 2, wherein the microfluidic component is selected from the group consisting of a micropump, a microelectrode, and a microvalve.

  The invention according to claim 4 as means for solving the above-mentioned problem is that the one or more ports, a substrate having a fine channel communicating with the port, and a facing surface bonded to the fine channel forming surface of the substrate In a microfluidic chip composed of a substrate, the horizontal portion of the substrate 3 is placed in a horizontal state with the micropump component 15 placed horizontally so that the micropump component 15 can be detachably mounted on the upper surface of at least one of the ports. The microfluidic chip is characterized in that it can be easily mounted and can be made compact as a whole.

  According to the present invention, a microfluidic component such as a micropump, a microelectrode, and a microvalve is built in polydimethylsiloxane or glass and assembled into a microfluidic component PDMS substrate port. The microfluidic component assembly can be self-adsorbed to the PDMS substrate by being placed on the top surface or inserted into the port. In a conventional microfluidic chip, micropumps and electrodes are discarded together with the chip after use, but according to the present invention, the microfluidic component assembly is detached from the PDMS substrate after using the microfluidic chip, These microfluidic component assemblies can be reused in another microfluidic chip, and significant cost reductions can be realized.

  Hereinafter, preferred embodiments of the present invention will be specifically described with reference to the drawings. FIG. 1 is a schematic sectional view of an example of a microfluidic chip 1 according to the present invention. The PDMS substrate 3 in the microfluidic chip 1 of the present invention is provided with a fine channel 5 and ports 7 and 9 communicating with the fine channel. The method of forming such a fine channel and port itself is described in Patent Document 1 and Patent Document 2, etc., and no further explanation is necessary. Needless to say, the PDMS substrate 3 has various channels such as a reaction vessel and a valve (for example, an on-off valve and / or a check valve) as necessary, in addition to the illustrated fine channel 5 and ports 7 and 9. Components can be formed. Further, the PDMS substrate 3 is not limited to the illustrated single layer, and a PDMS substrate having a multilayer structure in which two or more layers are laminated can also be used. For example, a glass facing substrate 10 is permanently bonded to the lower surface side of the PDMS substrate 3. Two or more fine channels 5 and ports 7 and 9 can be provided.

  In FIG. 1, a micropump assembly 11 is placed on the upper surface of the port 7. The micropump assembly 11 has an outer shell 13 and a micropump component 15 built in the outer shell 13. Lead wires 17 and 19 for driving the pump are connected to the micropump component 15. Needless to say, the other ends of the lead wires 17 and 19 are connected to an appropriate DC power source (not shown). A liquid storage space 21 is formed in the upper part of the micropump component 15, and a tube 23 for feeding the liquid into the liquid storage space 21 is fixed with an appropriate adhesive. The inner diameter of the port 7 can be appropriately determined according to the size of the micropump component 15. Since the entire outer shell 13 of the micropump assembly 11 is formed of PDMS, when the discharge side of the micropump component 15 is aligned and aligned with the port 7, the outer shell 13 made of PDMS becomes the PDMS. Permanently adheres to the upper surface of the substrate 3. After the intended analysis operation or the like is performed on the microfluidic chip 1, the micropump assembly 11 is peeled off from the PDMS substrate 3 and collected. Therefore, the micropump assembly 11 can be reused with another microfluidic chip.

  The micropump component 15 shown in FIG. 1 can be, for example, one in which an electrode is installed by packing before and after the porous membrane. The porous membrane is, for example, a nickel metal filter or a polycarbonate filter. The polycarbonate filter is commercially available from Sansho as an Isopore (registered trademark) membrane filter. This membrane consists of a polycarbonate film and is a track-etched screen filter recommended for any analysis where the sample is observed on the membrane surface. The polycarbonate filter has a pore diameter of 5 μm and a thickness of 11 μm. On the other hand, the pore diameter of the nickel metal filter is 5.01 μm and the thickness is 10 μm. When a voltage of several VDC to several tens of volts (for example, 2V to 15V) is applied between the electrodes before and after the film, the liquid flows from the anode side to the cathode side. Accordingly, the liquid in the liquid storage space 21 passes through the porous membrane and is pushed out into the port 7. The flow rate by this porous membrane pump can be changed within the range of 0.1 μL / s to 100 μL / s. The flow rate is roughly proportional to the applied voltage. When the polarity of the applied voltage is reversed, the flow direction of the liquid can be reversed. The advantage of using such a micropump component is that no pulsating flow occurs. This type of pump is “development of a micro flow pump using electroosmotic flow through a porous membrane”, Makoto Morita (Graduate School of Niigata University), et al. Published on January 27, pp. 359-360. The pump component 15 built in the PDMS outer shell 13 is not limited to the porous membrane type described above. Various types of micropump components can be used. For example, a micro pump using a unimorph vibration in which a piezoelectric element and a vibration plate are bonded together, a micro pump that vibrates a diaphragm with a piezoelectric element, a micro pump using a shear deformation of a piezoelectric element, and a diaphragm by electrostatic force A micro pump of a type to be deformed, a type of micro pump using a shape memory alloy as a part of the vibrator, and the like can be appropriately selected and used. The connection form of the tube 23 can be appropriately changed according to the pump to be used. For example, a configuration in which the tube 23 is connected to the input port of the pump and the output port of the pump is connected to the port 7 can be adopted.

  The material of the outer shell 13 is not limited to the above-described PDMS, but can be glass capable of self-adhesion with the PDMS substrate 3.

  FIG. 2 is a schematic sectional view of another example of the microfluidic chip 1 according to the present invention. In FIG. 2, another port 25 is formed in the middle of the fine flow path 5. An electrode assembly 27 is inserted into the port 25. The electrode assembly 27 is composed of a PDMS or glass body 29, and an electrode 31 is disposed on the lower surface of the body 29. A lead wire 33 is connected to the electrode 31. The electrode 31 is, for example, a conductive metal film such as platinum or gold. Such a metal film forming method is known to those skilled in the art. Since the main body 29 is formed of PDMS or glass, when the electrode assembly 27 is inserted into the port 25, the PDMS or glass main body 29 is permanently bonded to the inner wall surface of the port 25. After the intended analysis operation or the like is performed on the microfluidic chip 1, the electrode assembly 27 is peeled off from the inner wall surface of the port 25 and collected. Thus, the electrode assembly 27 can be reused with another microfluidic chip. In the case of a conventional microfluidic chip, such an electrode is formed on a glass facing substrate by printed wiring printing, etc., so after using the microfluidic chip, it is discarded together with the chip, and precious metal for the electrode is wasted. It was. However, the microfluidic chip of the present invention not only suppresses such precious metal waste, but also saves time and effort for printing printed wiring.

  The assembly inserted into the port 25 is not limited to the electrode assembly 27 shown in FIG. 2 but may be the micropump assembly 11 shown in FIG.

  A microfluidic chip having a cross-sectional structure as shown in FIG. 1 was produced. The facing substrate 10 was made of glass having a thickness of 1 mm, and the substrate 3 was made of PDMS having a thickness of 2 mm. The width and height of the microchannel 5 were 200 μm each, and the length (distance) was 50 mm. The inner diameter of the port 9 was 1 mm. The outer diameter of the outer shell 13 of the micropump assembly 11 was 20 mm, the height was 15 mm, and the inner diameter of the tube 23 was 3 mm. As the micropump component 15, a polycarbonate porous membrane having a pore diameter of 5 μm, a number of holes of 320,000, and a thickness of 11 μm was used. The outer diameter of the micropump component 15 was 13 mm and was built in the outer shell 13. In accordance with the size of the micropump component 15, the inner diameter of the port 7 was 9 mm. The micropump assembly 11 was aligned with the port 7 of the PDMS substrate 3 and self-adsorbed. Thereafter, a colloidal solution in which polystyrene particles (particle diameter: 0.12 μm) were dispersed at a concentration of 0.01% in ion-exchanged water (distilled water from which ions were removed) was fed from the tube 23 to the liquid storage space 21. A DC voltage was applied through electrode lead wires connected before and after the polycarbonate porous membrane to drive the micropump. A flow occurred from the anode side to the cathode side of the applied voltage. As a result, the polystyrene colloid solution in the liquid storage space 21 flowed from the port 7 to the port 9 through the fine flow path 5. The applied voltage was changed, and the flow rate corresponding to each voltage was measured. The results are shown in FIG. As is clear from the characteristic curve shown in FIG. 3, the liquid flow rate can be changed by adjusting the applied voltage.

  The micropump assembly 11 in Example 1 is peeled off from the microfluidic chip of Example 1 and self-adhered to the upper surface of the port 7 of another microfluidic chip having the same flow path structure, and the same polystyrene colloid as in Example 1 When a liquid feeding experiment was performed using the solution, the same result as in Example 1 was obtained. In addition, liquid leakage from the adhesion interface between the micropump assembly 11 and the PDMS substrate 3 did not occur. From this, it can be understood that the micropump assembly according to the present invention can be effectively used repeatedly as an external micropump in a microfluidic chip.

The preferred embodiments of the present invention have been described above with reference to the drawings. However, the present invention is not limited to only the illustrated embodiments. For example, not only one hole 7 but also a plurality of holes 7 in the PDMS substrate 3 can be arranged, and a necessary component assembly can be self-adsorbed in each hole. A removable component assembly such as a micropump can also be disposed in the hole 9. Furthermore, as the detachable component assembly, not only a micropump and an electrode but also a microvalve can be implemented.
As the liquid, a colloidal solution made of ion-exchanged water in which silica particles are dispersed can be used instead of polystyrene particles. Silica particles are cheaper than polystyrene particles and have great economic advantages.
Use of saline as a liquid is not preferable because electrolysis occurs after voltage application and bubbles are generated and the flow rate is temporally reduced. In the polystyrene colloid solution and the silica colloid solution, such bubble generation and temporal decrease in the flow rate are not observed, and the flow rate becomes constant.

It is a partial outline sectional view of an example of the microfluidic chip of the present invention. It is a partial outline sectional view of another example of a microfluidic chip of the present invention. FIG. 6 is a characteristic diagram showing a change in flow rate with respect to an applied voltage in Example 1.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microfluidic chip of this invention 3 PDMS board | substrate 5 Fine flow path 7 Input port 9 Output port 10 Face-to-face board | substrate 11 Micro pump assembly 13 PDMS outer shell 15 Pump components 17 and 19 Lead wire 21 Liquid storage space 23 Liquid supply tube 25 Port 27 Electrode assembly 29 Body 31 Electrode 33 Lead wire

Claims (4)

In a microfluidic chip comprising one or more ports, a substrate having a fine channel communicating with the port, and a facing substrate bonded to the fine channel forming surface of the substrate, at least one of the ports A microfluidic chip having a microfluidic component assembly that is placed on the upper surface of the port and is detachably self-adsorbed or inserted into the port and detachably self-adsorbed. The substrate is made of polydimethylsiloxane, the outer shell or body of the microfluidic component assembly is made of polydimethylsiloxane or glass, and the microfluidic component is built in the outer shell or body. The microfluidic chip according to claim 1. The microfluidic chip according to claim 1 or 2, wherein the microfluidic component is selected from the group consisting of a micropump, a microelectrode, and a microvalve. In a microfluidic chip comprising one or more ports, a substrate having a fine channel communicating with the port, and a facing substrate bonded to the fine channel forming surface of the substrate, at least one of the ports By mounting the horizontal part on the horizontal part of the substrate 3 in a state where the micropump component 15 is placed horizontally so that the micropump part 15 is detachably mounted on the upper surface of the port, the mounting is facilitated and the whole is made compact. A microfluidic chip characterized in that it can be used.

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