JP2005103423A - Microchemistry device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchemistry that is capable of modifying properties of the surface of a microchemistry device, particularly the surface properties of the selected same type of a substrate optionally or the surface properties of the different type of a substrate to the selected same properties almost without modifying the basic properties of the microchemistry device substrate. <P>SOLUTION: The microchemistry device is provided, wherein at least the part of a site which is in contact with the sample and/or medium or the solution is thinly coated by a coated layer comprised of a polycondensation compound using a metal alkoxide or a polycondensation compound using a mixture having a metal salt and/or a metal organic acid salt added to a metal alkoxide. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a microchemical device such as a microchip or a microreactor used for performing analysis, inspection, culture, reaction, or the like in a minute amount, and in particular, a sample used for performing analysis, inspection, culture, reaction, or the like. The present invention relates to a microchemical device made of a synthetic resin having a surface that has removed or enhanced interaction with a medium.

Recently, DNA analysis, polymerase chain reaction, separation by electrophoresis, cell response, cell Soteingu, reforming of the fuel for micro fuel cells, biochemical analysis, such as NO _X analysis, biochemical reactions, environmental analysis, trace chemical reactions, combinatorial In order to perform various analyzes and reactions such as chemistry or combinatorial bioengineering analysis or reaction at high throughput (many, in a short time or simply) or under high-precision uniform conditions, Development of microchemical devices such as microchips and microreactors that can be used for reaction is progressing.

  In general, a microchemical device absorbs an external gas into a liquid (inside the device), a fine channel (channel) or a container (well) on a small normal flat plate, which is a base (a main component of the microchemical device). The diaphragm or the electrode or the connector that is an interface with the outside is integrated and formed as necessary, and these fine channels and containers are used to make the above-mentioned Analyze and react.

  In the present invention, a device in which at least one or many channels or / and containers as described below are installed is referred to as a microchemical device. That is, the size of the fine channel installed on the substrate has a width and depth in the range of 1 to 1000 μm, preferably 10 to 500 μm, more preferably 30 to 300 μm, and the size of the container installed on the substrate. When the shape of the container is a square, its maximum side and depth are, and when it is a circle or ellipse, its diameter or major axis and depth is 1-1000 μm, preferably 10-500 μm. In this microchemical device, it is sufficient that at least the flow path or container in the above-mentioned range is installed. Therefore, a flow path or container outside the above range may be installed at the same time. Other functions may be installed at the same time. Such microchemical devices are used for separation, analysis, inspection, diagnosis, reaction, culture, and the like.

  In general, the finer the flow path and the container (chamber), the larger the specific surface area, and the effect on the surface becomes dominant. In the micro scale, the heat exchange efficiency is relatively high as compared with the macro scale, the molecular diffusion effect is increased, and the liquid flow becomes a laminar flow. Therefore, in a microchemical device that actively uses such physical properties, it is important to control the surface state of the flow path and the container.

  In general, glass, synthetic resin, metal, ceramic, or the like is used as a base material constituting these microchemical devices.

  However, the characteristics of the surface of a microchemical device using such a material are determined by the material of the substrate itself. For example, even if a sample such as DNA or a cell is transported through a channel by a medium, the sample If the affinity between the microchemical device and the microchemical device surface is strong, the sample may be left behind from the flow of the medium, and normal analysis and reaction may not be performed. On the other hand, if an analysis or reaction technique that uses the interaction between the sample and the surface of the microchemical device channel is employed, this may not be achieved.

As one method for solving such problems, when the material constituting the microchemical device is hydrophobic, in order to make it hydrophilic, microchemical using a material in which a hydrophilic polymer is mixed with a hydrophobic polymer. Improvements such as creating a device have been proposed (Patent Document 1). However, this method improves the surface properties, but because the polymer is mixed as the material constituting the substrate, physical properties other than the surface properties of the microchemical device substrate (for example, moldability, transparency, heat resistance, etc.) are reduced. A problem occurred.
Japanese Patent Application No. 2001-363121

  In the present invention, the surface characteristics of the microchemical device surface, the surface characteristics of the same kind of selected substrate, or the surface characteristics of different types of substrates can be selected without changing the basic physical properties of the microchemical device substrate. The problem of the prior art is solved by making it possible to change to the same characteristic.

  That is, in the present invention, the microchemical device as described above can be easily manufactured and mass-produced at low cost, and the surface chemistry of the surface where the sample or medium used for analysis or reaction is in contact with the microchemical device. Properties (specifically, surface free energy, experimental contact value of water contact angle) can be arbitrarily changed over a wide range so that required analyzes and reactions can be performed at high throughput. It is a task to do.

  In order to solve the above-described problems, the present invention provides a method in which at least a part of a site where the sample or / and the medium or the solution is in contact is a polycondensation compound using a metal alkoxide, or a metal salt or / and a metal organic compound. A microchemical device is provided which is thinly coated with a coating layer made of a condensation polymerization compound using a mixture to which an acid salt is added (Claim 1).

  Further, in order to solve the above-mentioned problems, the present invention provides a method in which at least a part of a portion where the sample or / and the medium or the solution is in contact is in a polycondensation compound using a metal alkoxide or in a metal alkoxide. A microchemical device characterized by being thinly coated with a coating layer in which a metal colloid or a metal oxide colloid is dispersed in a condensation polymerization compound using a mixture to which a metal organic acid salt is added. (Claim 2).

  Here, the main material constituting the substrate of the microchemical device is preferably a thermoplastic synthetic resin or a thermosetting synthetic resin.

  The main materials constituting the substrate of the microchemical device are polymethyl methacrylate, polycarbonate, polydimethylsiloxane, polystyrene, polyethersulfone, polysulfone, polyethylene terephthalate, polybutylene terephthalate, polyphenylene sulfide, polyetherimide, polypropylene, poly It is also preferable to consist of at least one of cycloolefin and polyperfluoroalkoxy resin.

  The metal alkoxide, metal salt or metal organic acid salt, which is a raw material constituting the main material of the coating layer covering at least a part of the microchemical device, is silicon, zirconium, titanium, boron, aluminum, nickel, Preferably, it is at least one of tantalum, calcium, magnesium, zinc, and phosphoric acid ester (Claim 5).

  The material of the coating layer that covers at least a part of the microchemical device is at least one of tetraethyl silicate, trimethyl borate, zirconium butoxide, titanium propoxide, aluminum butoxide, zinc chloride, titanium oxide, and ethoxytrimethylsilane. It is preferable that it is 1 type (Claim 6).

  In coating the surface of the microchemical device, it is also preferable to form a surface coating on the microchemical device substrate after applying a primer.

  As described above in detail, according to the present invention, the surface chemical characteristics of the microchemical device can be arbitrarily set according to the purpose of use, so that highly accurate or high-throughput analysis and reaction can be performed. A range of uses for chemical devices is possible. In addition, since a microchemical device made of a synthetic resin and having excellent surface characteristics can be easily manufactured in large quantities by an injection molding method or the like, and the surface treatment can be easily performed, the microchemical device can be provided at low cost.

  Hereinafter, a microchemical device according to an embodiment of the present invention will be described.

  In the present invention, in order to solve the above-described problems, a polychemical compound using a metal alkoxide, or a metal salt or / and a metal organic acid using a metal alkoxide on the surface of a microchemical device sample or / and a medium contacting the surface. In a coating layer composed of a polycondensation compound using a mixture to which a salt is added, or in a polycondensation compound using a metal alkoxide, or using a mixture in which a metal salt or / and a metal organic acid salt is added to the metal alkoxide. The polymer compound was thinly coated with a coating layer in which a metal colloid or metal oxide colloid was dispersed, so that the contact angle with water on the surface of the microchemical device could be arbitrarily set over a wide range. The present invention is characterized in that a so-called sol-gel method is used to form a coating layer at a necessary portion of a microchemical device to form a surface having a desired water contact angle.

  In the microchemical device of the present invention, for example, a thermoplastic or thermosetting synthetic resin can be used as a main material constituting the substrate, and fine flow paths and wells can be easily formed on the surface of the microchemical device by injection molding or the like. Furthermore, a coating layer made of a polycondensation compound using a polycondensation compound using a metal alkoxide, or a mixture obtained by adding a metal salt or / and a metal organic acid salt to a metal alkoxide, or a metal alkoxide was used. The surface is covered with a coating layer in which metal colloid or metal oxide colloid is dispersed in a polycondensation compound or in a polycondensation compound using a mixture of a metal alkoxide and a metal salt or / and a metal organic acid salt. Thin coating makes it easy to manufacture high-quality microchemical devices and enables mass production at low cost. It is possible to provide.

  In addition, as described above, the surface of this microchemical device can be modified to match the purpose corresponding to the intended analysis and reaction, so that these analysis and reaction can be performed accurately or at high throughput. It becomes like this.

  Since the surface of the microchemical device of the present invention is coated with another type of material as described above after the substrate is molded, the substrate material of the microchemical device is suitable for the substrate from an appropriate moldability and intended use. Any synthetic resin can be selected as long as it satisfies the required characteristics (for example, transparency and heat resistance). For example, polymethacrylate such as polymethyl methacrylate, polycarbonate, polystyrene, ABS, aromatic polyester such as polyethylene terephthalate and polybutylene terephthalate, various polyolefins such as polypropylene and polycycloolefin, polysulfone, polyethersulfone, polyphenylene sulfide, poly In addition to thermoplastic synthetic resins such as lactic acid and polyperfluoroalkoxy resins, thermosetting synthetic resins such as polydimethylsiloxane and polytetrafluoroethylene can also be used.

  These synthetic resins may be used alone or in combination of two or more as required. Alternatively, a microchemical device in which two or more kinds of individual synthetic resins are arranged at different positions of the microchemical device can be configured by using a multicolor molding method or the like. Further, depending on the purpose of use, additives such as carbon black, graphite, titanium oxide, and zinc oxide can be mixed with the above synthetic resin. When carbon black or graphite is added, the generation of autofluorescence of the microchemical device substrate can be suppressed and the accuracy of analysis can be increased.

  Metals of metal alkoxide, metal salt or metal organic acid salt, which are the raw materials constituting the main material of the coating layer covering at least a part of the microchemical device, are silicon, zirconium, titanium, boron, aluminum, nickel, tantalum, It is at least one of calcium, magnesium, zinc and phosphorus.

  A polycondensation compound using a metal alkoxide, or a polycondensation compound using a mixture obtained by adding a metal salt or / and a metal organic acid salt to a metal alkoxide can be obtained by mixing the main materials and performing a sol-gel reaction. In the sol-gel reaction, after mixing main materials, the metal alkoxide is hydrolyzed by water obtained by ester reaction of acetic acid and alcohol, or water obtained by direct dropwise addition, and the metal-containing polycondensation compound is converted into a sol-gel reaction. can get.

  It is also possible to disperse metal colloids or metal oxide colloids in polycondensation compounds using metal alkoxide or polycondensation compounds using a mixture of metal alkoxide and a metal salt or / and metal organic acid salt. It is.

  The polycondensation compound thus produced is coated on a substrate by a method such as spin coating, dipping, or screen printing. At that time, in order to increase the adhesion to the substrate, it is also possible to coat the polycondensation compound after applying an undercoat. Examples of the material used for the undercoating include a resin and a condensation polymerization compound, and examples of the resin material include acrylic, and the condensation polymerization compound is a resin or a coating material used for the top coating or a coating material used for the top coating. What added / and metal oxide or / and metal colloid can be used.

  The substrate coated with the condensation polymerization compound is heated at a temperature of room temperature to 300 ° C., preferably 50 ° C. to 150 ° C., to dry and solidify the condensation polymerization compound.

  A metal alkoxide, a metal salt or a metal organic acid salt is selected from at least one or more, and 1 to n moles of water, nitric acid, hydrochloric acid and other catalysts are added to ethanol per mole of a metal element (oxidation number n), A liquid obtained by hydrolysis in a solvent of isopropanol, n-butanol and sec-butanol is applied to a microchemical device substrate to form an oxide film. In the hydrolysis, Ti, Zr, Ta, Nb, and Al are added with acetylacetone, ethyl acetoacetate, methyl acetoacetate, acetic acid, monoethanolamine, and diethanolamine as stabilizers. Table 1 lists the compositions of Examples 1-12. The compounds a, b and c in the table can also be added to these compositions. Here, a is 3-aminopropyltriethoxysilane (3-Aminopropyltriethoxysilane), b is 3-Glycidyloxypropyltrimethoxysilane, and c is tris (1,1,1,3,3,3- Hexafluoroisopropyl) ethoxysilane {Tris (1,1,1,3,3,3-Hexafluoro-isopropyl) ethoxysilane}.

  The synthesized coating agent can be applied to the target resin surface by a technique such as spin coating or dipping, and dried appropriately at a temperature from room temperature to 180 ° C. to form a film. When the surface further requires water repellency, the fluorine compound c in the table or triethoxy-1,1,2,2-tetrafluoro-n-octylsilane (Triethoxy-1,1,2,2-tetrafluoro) -n-octylsilane) can be accommodated, and when further hydrophilicity is required, it can be accommodated by treatment with water vapor after film formation.

  Selection of the solvent for the coating agent is not limited to those described above, and the composition dissolves, and any solvent can be used as long as it can form a film.

  The composition described in Example 12 in Table 1 was thinly applied to the surface of an injection-molded article made of polycarbonate, polymethyl methacrylate, or polyetherimide, and further treated with water vapor. As a result, the contact angle of water on the surface of the uncoated product was 72 ° to 80 °, whereas the contact angle of water on the surface of these coated water treated products was 32 ° to 40 °. In addition, the contact angle of water in glass, which is a typical hydrophilic material, is 30 ° to 40 °.

  Here, the contact angle of water is such that water is dropped from a height of 50 mm with a syringe having a droplet size of 20 μL onto the surface of a horizontally placed test piece, and the water drop is parallel to the surface of the test piece. The photograph was photographed, and at the boundary line where the test piece, water droplet and air contacted, the angle on the water drop side was determined by measuring the angle between the water drop surface and the test piece surface. This contact angle was measured for each test piece under the same atmosphere (temperature 25 ° C., humidity 60 RH), and was calculated as the average value of the values measured at three locations on each test piece.

1 to 4, a plurality of tapered through holes 2 having a large diameter on the front surface side and a small diameter on the back surface side are formed in a base plate 1 made of polymethyl methacrylate, and each through hole is formed. A groove 3 having a continuous width of 100 μm and a depth of 50 μm is provided to connect the small diameter sides of 2 and 2, that is, the groove 3 is provided on the back side of the base plate 1, and polymethyl methacrylate is also used on the back side of the base plate 1. A microchip A to which the cover sheet 4 having a thickness of 50 μm was adhered was produced. This microchip A has a structure having liquid reservoirs 6 and 6 formed by through holes 2 and a cover sheet 4 at both ends of a pipe-shaped channel 5 formed by a groove 3 and a cover sheet 4. Chip. The composition described in Example 12 in Table 1 was thinly applied to the inside of the channel 5 of the microchip A, and further subjected to steam treatment. Here, in order to inject the composition described in Example 12 of Table 1 into the thin channel 5, the pressure is applied under pressure or under reduced pressure. And the reduced pressure drying means was used for the subsequent drying process. By this treatment, a SiO ₂ film having a thickness of 1 μm or less was formed on the inner surface of the channel 5.

  Then, when water was dropped from a spoid into the liquid reservoir 6 of the channel 5 of the microchip A, the water was automatically filled into the channel 5 immediately by capillary action. On the other hand, even when water was dropped from the spoid into the liquid reservoir 6 of the uncoated channel 5, the water was not filled into the channel 5 at all. In order to supply water into the uncoated channel 5, it was necessary to press-fit water with the outlet of the spoid in close contact with the liquid reservoir 6.

It is a top view of the microchip for electrophoresis. It is an exploded perspective view similarly. It is an enlarged sectional view similarly. It is a partially expanded sectional view of a channel part.

Explanation of symbols

A Microchip 1 Base plate 2 Through hole 3 Groove 4 Cover sheet 5 Channel 6 Liquid reservoir

Claims (7)

  A polycondensation compound using a polycondensation compound using a metal alkoxide, or a mixture obtained by adding a metal salt or / and a metal organic acid salt to a metal alkoxide, at least a part of the site where the sample or / and the medium or solution contacts A microchemical device characterized by being thinly coated with a coating layer comprising:   At least a part of the site where the sample or / and the medium or the solution is in contact was used in a polycondensation compound using a metal alkoxide or a mixture obtained by adding a metal salt or / and a metal organic acid salt to the metal alkoxide. A microchemical device which is thinly coated with a coating layer in which a metal colloid or a metal oxide colloid is dispersed in a condensation polymerization compound.   The microchemical device according to claim 1 or 2, wherein a main material constituting the substrate of the microchemical device is a thermoplastic synthetic resin or a thermosetting synthetic resin.   The main materials constituting the substrate of microchemical devices are polymethyl methacrylate, polycarbonate, polydimethylsiloxane, polystyrene, polyethersulfone, polysulfone, polyethylene terephthalate, polybutylene terephthalate, polyphenylene sulfide, polyetherimide, polypropylene, polycyclohexane. The microchemical device according to claim 1 or 2, comprising at least one of olefin and polyperfluoroalkoxy resin.   Metal alkoxide, metal salt or metal organic acid salt, which is a raw material constituting the main material of the coating layer covering at least a part of the microchemical device, is silicon, zirconium, titanium, boron, aluminum, nickel, tantalum, The microchemical device according to any one of claims 1 to 4, which is at least one of calcium, magnesium, zinc, and phosphate.   The material of the coating layer that covers at least a part of the microchemical device is at least one of tetraethyl silicate, trimethyl borate, zirconium butoxide, titanium propoxide, aluminum butoxide, zinc chloride, titanium oxide, and ethoxytrimethylsilane. It is a seed | species, The microchemical device of any one of Claims 1-4. The microchemical device according to any one of claims 1 to 6, wherein, when the surface of the microchemical device is coated, after the microchemical device substrate is primed, a surface coating is formed thereon.

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