JP4581784B2 - Method for producing a mold for producing a microchannel substrate - Google Patents

Description

  The present invention relates to a method for producing a mold for producing a plastic microchannel substrate having smooth and fine microchannel protrusions, and a plastic microchip substrate produced using the mold.

    Recently, research on miniaturization of chemical reactions and separation systems using microfabrication technology called microreactor and micrototal analysis system (μTAS) has become active, and nucleic acids, proteins, It is expected to be applied to the analysis and synthesis of sugar chains, rapid analysis of trace chemicals, and high-throughput screening of pharmaceuticals and drugs. Advantages of such system microfabrication include: (1) The amount of samples and reagents used in chemical reactions and antigen-antibody reactions can be reduced, and the amount of waste can be reduced. (2) The power source required for the process can be reduced. (3) By increasing the ratio of the surface area to the volume, it is possible to increase the speed of heat transfer and mass transfer. As a result, precise control of reaction and separation, high speed and high efficiency, and suppression of side reactions are expected. (4) It is possible to handle many samples at the same time on the same substrate, (5) It is possible to carry out from sampling to detection on the same substrate, etc. Realization is being considered. On the other hand, there are many disadvantages: (1) Detection sensitivity decreases because the detection area is small. (2) It is difficult to generate turbulent flow in a microscale fluid flow. (3) When bubbles or the like are generated, it is difficult to remove the influence of the surface tension greatly, and the measurement system is often greatly affected. Under these merits and demerits, microfluidics technology is being studied. In the automotive industry, acceleration sensors, pressure sensors, position sensors (gyroscopes), etc. In the telecommunications industry, optical waveguides, optical switches, mirrors, and lenses. In the life science industry, blood analysis, DNA analysis, chemical crime investigation use, etc. are found in our daily lives. Other applications include food, environmental testing, and munitions. The microfluidics technology currently being developed has many sensor applications, and microsensors using enzymes or antigen-antibody reactions, ion-sensitive field effect (ISFET), microelectrodes, microcantilevers, acoustic waves, and resonance have been reported. Yes. There have been many reports on applications such as microelectrophoresis chips, micro PCR (Plymerase Chain Reaction) chips, micro gas chromatography chips, micro liquid chromatography chips, DNA separation chips, and the like. The development of Lab-on-a-Chip that performs sampling to analysis on the same chip has also been reported. Multifunctional biochips using nucleic acids and antibodies specific to Bacillus anthracis and Escherichia coli, glucose, lactose, etc. A portable measuring device for monitoring the blood pressure, a clinical test chip using an antigen-antibody reaction, and the like.

In the early 1990s, silicon wafers were used as materials for microfluidics, μTAS, and Lab-on-a-Chip devices due to the influence of the mature electronics industry and manufacturing technology using completed silicon wafers. However, while electrical methods (electroosmosis method) are actively developed as fluid transport methods, high voltage is applied to maintain electrical liquid transport due to the low electrical conductivity and breakdown voltage of silicon. Restrictions have arisen on the use of silicon materials for applications that require. In addition, the surface of the silicon wafer is likely to chemically adsorb biological macromolecules (DNA, peptides, proteins), and there is a high risk of increasing non-specific adsorption. Therefore, treatment to prevent non-specific adsorption on the silicon wafer. Is not suitable for applications that use optical detection, etc., and the cost of raw materials may be high.Furthermore, for microfluidics applications, especially for diagnostic microfluidics applications where disposables are essential. It has been considered unsuitable.
Microfluidics manufacturing technology using silicon wafers is a chemical etching method that uses the microfabrication technology cultivated in IC manufacturing technology and the etching rate and etching characteristics depending on the crystal orientation of the silicon wafer or the type of etchant. Researchers pay attention because special microfluidic fabrication methods have been developed on silicon wafers, such as an anisotropic etching method, a plasma etching method that is a physical etching method, and an etching method that uses a sacrificial layer. Although there is an electrothermal fusion method as an adhesion method for silicon wafer microfluidics, it is easy to cause damage to the surface due to electrical conduction at high temperature, and there is also an adhesion method using an adhesive, It is said that there are problems with strength and reliability. It has become one of the stomach microfluidics drawbacks.

Microfluidics fabrication processes have been established using glass materials as new materials other than silicon wafers. Glass materials are attracting attention as a major material in developing microfluidics, μTAS, and Lab-on-a-Chip devices thanks to established manufacturing technologies, and microfluidics also in terms of surface characteristics and material characteristics. It has been considered an excellent material for devices. However, glass materials suffer from high microfluidic manufacturing costs and lack of mass production technology when commercializing microfluidic technology. The manufacturing cost is mainly the material price and the cost in the manufacturing process. In the case of glass, although it is relatively cheaper than a silicon wafer, cleaning, metal deposition, resist coating, wet etching, and substrate bonding processes are performed for each substrate. This is a complicated and expensive process. Among them, the processes that are problems are an etching process and an adhesion process. In the etching process, an etchant using a strong acid such as hydrogen fluoride (HF) or a mixture of hydrogen fluoride (HF) and nitric acid (HNO ₃ ) is used. However, the etching rate is very slow, 2 μm to 7 μm / min, and the production capability is lowered. It is conceivable to increase the etchant concentration in order to improve the etching rate, but there is a limit because the surface smoothness deteriorates. In addition, since a strong acid is used as an etchant, a pattern mask in which gold (Au) that is not attacked by a strong acid is deposited on the surface of the glass substrate is required. Since this is not possible, a chromium (Cr) layer is required as an adhesive layer. The gold (Au) film for the pattern mask is required to have a thickness of 300 nm or more so that no pinhole is generated. Furthermore, wet etching of glass has limitations when etching geometric designs because glass is an isotropic material. A microfluidic design often requires high aspect ratio channels, square or rectangular channels, and a chip using a glass material cannot easily meet these requirements. In the bonding process, it is necessary to process at a high temperature of several hundred degrees. Even if the electrothermal fusion method is used, there is a problem similar to that of a silicon wafer (Non-Patent Document 1).

Under such circumstances, it has been gradually found that there are many advantages to using plastic as a material for microfluidics, μTAS, Lab-on-a-Chip devices. Plastic materials are much cheaper than silicon wafers and glass materials, and well-established, low-cost manufacturing technologies such as injection molding, embossing, casting, and cutting can be used. Various plastic materials can be selected. The selection range is very large even with a commercially available material alone. For example, PC (Polycarbonate), PMMA, COC, epoxy, PDMA (Poly (dimethyl Siloxane)) and the like are listed as options. Among these, COC is recognized as a bioadaptive material (no problem even if it comes into contact with blood) by the FDA and is considered a promising material.
Examples of microfabrication technology for plastic materials include injection molding using a mold, hot embossing, mold, etc. Among them, the injection molding method is suitable for mass production and has attracted attention. Examples of plastic processing methods that do not use a mold include a cutting method (Patent Document 1) in which a microchannel is directly formed on a plastic by an end mill, and a laser method in which a microchannel is formed on a plastic substrate with a laser beam. Currently, it is practically used only at the prototype level for research purposes. In injection molding, a molten thermoplastic material is introduced into a mold cavity, the cavity is cooled, and the resin is cured, so that a microchip substrate can be manufactured efficiently and economically, which is suitable for mass production. The hot embossing method is a method in which a mold is pressed onto a plastic substrate heated near the glass transition point (Tg) to transfer the shape of the mold. Is inferior to the injection molding method. The mold method is a method for producing a microchannel by pouring a photo-curing resin or a thermosetting resin into a micro-processed mold and polymerizing the mold by applying ultraviolet rays, an electron beam, or heat, and releasing the mold. Since curable plastics can be processed at low temperatures, it is possible to fabricate microchip substrates without damaging equipment or devices due to heat or vibration, but they are suitable for prototyping because of their long reaction curing time and cooling time. Is not suitable for mass production.

Many researchers have focused on a mold manufacturing technique that can process a channel of 10 μm level as a mold manufacturing technique. In the early 1980's, Karlsruhe Research Center (Germany) developed a LIGA technology that can be adapted to microfluidic production. “LIGA” is an abbreviation for German Lithography (lithography), Galvanoforming (electroplating), and Abforming (replication). In this LIGA process, a PMMA resist is exposed and developed with X-rays through a photomask for X-rays, and then a mold (cavity) is manufactured by electroplating (electroforming), and a plastic microchannel substrate using the mold Is produced. Later, UV-LIGA was developed that uses UV light instead of X-ray exposure. Compared with LIGA using X-rays, the aspect ratio is reduced, but when cost is taken into consideration, the UV-LIGA technology is also an excellent technology. In addition, Si, glass, metal plates processed by wet etching and dry etching methods, and electroplating of metals such as Ni using glass, plastic, metal plates, etc. processed by cutting methods using an end mill as an original plate ( There is also a method in which a mold is produced by electroforming, and a plastic microchannel substrate is produced using the mold. In these mold manufacturing methods, an electroforming process is indispensable, but an ordinary mold manufacturing method requires an electroforming thickness of about 20 to 30 mm including a base as a base. In general, nickel (Ni) is often used as an electroforming material for molds, and there is a limitation on the current density that can be applied to perform precision and dense electroforming of thick films with little internal stress. Therefore, generally, the electroforming speed is 10 to 20 μm / hr. In order to electrocast a thickness of 20 to 30 mm, a long processing time of 1000 to 3000 hours is required. In order to solve this problem, a method of applying a photoresist on a metal plate, patterning it into a microchannel shape using LIGA or UV-LIGA photolithography, and forming only the microchannel portion by electroforming is also employed. . The depth of the microchannel is usually about 20 to 150 μm, and the electroforming time is 1 to 15 hours, which is a very useful production method, which is shortened compared with a general method.
With these processing techniques, it is possible to produce a plastic microchannel substrate with relatively good performance. However, there are still problems with plastic microchannel substrates, and their practical application is insufficient. There are various problems, but one of them is insufficient surface smoothness. In order to detect a chemical substance to be analyzed or produced, usually an optical detection device such as confirmation of fluorescence intensity, detection by a thermal lens microscope, detection by IR spectrum or UV spectrum is suitably performed. In many cases, light is incident on the chip and the intensity of the light is confirmed from the opposite surface or the incident surface. Therefore, if the surface smoothness of the bottom of the microchannel is low, regardless of whether it is made of plastic or non-plastic, the detection sensitivity of the chemical substance to be analyzed or produced is greatly reduced. There is a demand (Patent Document 2).
Nobuaki Honda, Chemical Engineering, Vol. 66, No. 2, P71-74 (2002) JP 2002-210609 A Japanese Patent Laid-Open No. 2004-340752

    The object of the present invention is that the surface smoothness is low because the liquid flow and the detection sensitivity of the chemical substance to be analyzed or produced are greatly reduced due to the low surface smoothness of the bottom of the microchannel, and there is a problem in detecting trace substances. An object of the present invention is to provide a plastic microchannel substrate having a microchannel bottom having a very high surface smoothness by producing a mold having excellent microchannel-like projections and further using this mold.

The present invention is as follows.

(1) A method for producing a mold for producing a microchannel substrate having a metal protrusion for forming a microchannel having a width of 1 mm or less and a height of 1 mm or less on a metal substrate,
(1) A step of forming a macro channel projection and a dummy projection on a metal substrate ,
The process in which the height of the dummy protrusion is greater than the height of the microchannel protrusion
(2) and a step of polishing the upper surface portion of the microchannel-like protrusion and the upper surface of the dummy protrusion,
Only including,
Forming a macro-channel-shaped protrusion and a dummy protrusion on the metal substrate;
(A) A step of etching or cutting a silicon substrate, a glass substrate, or a plastic substrate to produce an original plate,
(B) and a process of electroforming metal on the original plate
Or
(C) a step of coating a photoresist on a metal substrate;
(D) patterning a photoresist by photolithography,
(E) and a step of electroforming metal on the patterned portion,
A method for producing a mold for producing a microchannel substrate, wherein
( 2 ) The method for producing a template for producing a microchannel substrate according to ( 1 ), wherein the microchannel-like protrusion and the dummy protrusion are a metal containing nickel.
(3) the metal substrate is made of metal containing nickel (1) or (2) a method for manufacturing a microchannel substrate fabrication mold of any one.
( 4 ) In the step of polishing the upper surface portion of the microchannel-shaped protrusion and the upper surface of the dummy protrusion,
The method for producing a template for producing a microchannel substrate according to any one of (1) to ( 3 ), including a step of polishing by a CMP (Chemical Mechanical Polishing) method.
( 5 ) The method for producing a template for producing a microchannel substrate according to any one of (1) to ( 4 ), wherein the surface roughness (Ra) of the upper surface of the metal projection for forming the microchannel is 0.2 μm or less.
( 6 ) A mold for producing a microchannel substrate produced by the method for producing a template for producing a microchannel substrate according to any one of (1) to ( 5 ).
( 7 ) A plastic microchip substrate, wherein a microchannel is formed on a plastic substrate using the microchannel substrate production mold described in ( 6 ).
( 8 ) The plastic microchip substrate according to ( 7 ), wherein the surface roughness (Ra) of the bottom of the microchannel is 0.2 μm or less.
( 9 ) The plastic microchip substrate according to ( 7 ) or ( 8 ), wherein the plastic substrate is composed of a saturated cyclic polyolefin.
( 10 ) ( 7 ) to ( 9 ) A micro-chip in which a bioactive substance containing at least one of nucleic acid, protein, sugar chain, and glycoprotein is immobilized on a part of a microchannel of the plastic microchip substrate. Chip substrate.

By using the production method of the present invention, a mold having microchannel-like protrusions with excellent surface smoothness can be produced, and further using this mold, the bottom of the microchannel has a very high surface smoothness, and a liquid It is possible to fabricate a high-performance microchannel substrate that does not have any problem in the flow of liquid and detection of trace substances.

Hereinafter, the present invention will be described in detail.
FIG. 1 is a schematic cross-sectional view showing an embodiment of a method for producing a mold for producing a microchannel substrate according to the present invention.
FIG. 1A shows a case in which metal electroforming is performed on an original plate 1 prepared by etching or cutting a silicon substrate, a glass substrate, or a plastic substrate. The material of the original plate is preferably silicon, glass, plastic or the like because it is generally used and processing techniques are accumulated, but it is not particularly limited to this material. As a processing method, an etching method or a cutting method is preferably used and is not particularly limited as long as the microchannel can be processed on the substrate.
FIG. 1B shows a metal mold 2 obtained by electroforming and transferring a metal from an original plate. The material to be electroformed is preferably nickel (Ni) or a material containing nickel (Ni) because it has mechanical properties and hardness, and is generally used in electroforming and has established mass production technology, but injection molding, hot embossing, etc. There is no particular limitation as long as electroforming can be performed on the surface of the metal plate without any mechanical, chemical, and thermal problems in processing. Even in such a mold, plastic can be molded by the injection molding method, hot embossing method, or mold method. However, the microchannel surface is not smooth and can be used for microchips that do not require precision, but the optical detection is highly accurate. It cannot be used for microchips that use.
FIG. 1C is a cross-sectional view after the microchannel-like protruding portion 3 and the dummy protruding portion 4 are polished together. Since the microchannel protrusions are polished together with the dummy portions, the pressure during polishing is dispersed in the microchannel portions and the dummy portions, so that the microchannel electroformed portions are prevented from being deformed or missing. Since the dummy part serves to protect the microchannel electroformed part from deformation due to pressure and shear force during the polishing process, it is preferably thicker than the thickness of the microchannel part, and the area larger than the microchannel part is polished. This is preferable because the pressure can be dispersed in the microchannel portion.
As a polishing method, CMP (Chemical Mechanical Polishing) has been established for polishing Si wafers and the like, and it is desirable because it can produce extremely excellent surface smoothness. However, lapping used for polishing glasses lenses and contact lenses is desirable. There is no particular limitation as long as it is a polishing method capable of producing desired surface smoothness, such as a polishing method using a film and a buffing method used when polishing a metal material. The surface roughness (Ra) of the upper surface portion of the microchannel protrusion is preferably 0.2 μm or less, more preferably 0.1 μm or less. If the surface roughness (Ra) of the upper surface of the microchannel protrusion exceeds 0.2 μm, the surface of the plastic microchannel to be transferred has the same level of surface property, so detection using an optical system such as a thermal lens microscope May be impossible to detect with the instrument.
A plastic microchannel substrate is manufactured by using an injection molding method, a hot embossing method, and a template method using the template thus prepared. The surface roughness (Ra) of the microchannel bottom of the produced plastic microchannel substrate is preferably 0.2 μm or less, more preferably 0.1 μm or less. If the surface roughness (Ra) of the upper surface of the microchannel projection exceeds 0.2 μm, it may be impossible to detect with a detector using an optical system such as a thermal lens microscope.

FIG. 2 is a schematic cross-sectional view showing another embodiment of a method for producing a mold for producing a microchannel substrate according to the present invention.
FIG. 2A shows a state in which a photoresist 6 is applied on the metal plate 5. The metal plate is preferably nickel (Ni) or a metal material containing nickel (Ni) because it is widely used as a material for mechanical strength and hardness, electroforming, but mechanical for injection molding, hot embossing, etc. There is no particular limitation as long as electroforming can be performed on the metal plate surface without any chemical or thermal problems. The thickness of the photoresist is appropriately determined depending on the depth of the microchannel to be manufactured. When the thickness of the photoresist becomes thinner than the target microchannel depth, it is impossible to produce a microchannel that protrudes well from the pattern portion of the photoresist when electroformed. In addition, as a method for applying the photoresist, there are techniques such as spin coating, bar coating, die coating, and screen printing, but there is no particular limitation.
FIG. 2B is a cross-sectional view after patterning the photoresist, and the patterned portions 7 and 8 have the metal portions exposed on the surface but the other portions covered with the photoresist and not exposed. It is. The exposure and development conditions for the photoresist are processed under conditions that are appropriately optimized in consideration of the type of photoresist, coating thickness, and the like.
FIG. 2C is a cross-sectional view when a metal is electroformed by electroforming on a metal plate patterned with a photoresist. Only a portion where the metal plate is exposed is electroformed, and a metal portion 9 electroformed into a microchannel shape by a photoresist patterned in a microchannel shape and a dummy shape, and a metal portion 10 electroformed into a dummy shape are on the metal plate. It is convex. The thickness of the electroforming process is appropriately determined depending on the depth of the microchannel to be manufactured, but it is desirable that the thickness be about 10 to 30 μm thicker than the thickness of the microchannel to be manufactured. In order to improve the surface smoothness of the upper part of the microchannel-shaped protrusions electroformed after the electroforming process, it is necessary to electrocast the thickness including the cutting allowance. If the thickness is less than 10 μm, the desired surface smoothness may not be obtained because the shaving margin is small. The material to be electroformed is preferably nickel (Ni) or a material containing nickel (Ni) because it has mechanical properties and hardness, and is generally used in electroforming and has established mass production technology, but injection molding, hot embossing, etc. There is no particular limitation as long as electroforming can be performed on the surface of the metal plate without any mechanical, chemical, and thermal problems in processing.
FIG. 2D is a cross-sectional view after removing all the remaining photoresist, and is a cross-sectional view of the mold before the polishing process. Even in such a mold, plastic can be molded by the injection molding method, hot embossing method, or mold method. However, the microchannel surface is not smooth and can be used for microchips that do not require precision, but the optical detection is highly accurate. It cannot be used for microchips that use.
FIG. 2 (e) is a cross-sectional view after the microchannel-like protruding portion 9 and the dummy protruding portion 10 are polished together. Since the microchannel protrusions are polished together with the dummy portions, the pressure during polishing is dispersed in the microchannel portions and the dummy portions, so that the microchannel electroformed portions are prevented from being deformed or missing. Since the dummy part serves to protect the microchannel electroformed part from deformation due to pressure and shear force during the polishing process, it is preferably thicker than the thickness of the microchannel part, and the area larger than the microchannel part is polished. This is preferable because the pressure can be dispersed in the microchannel portion. As a polishing method, CMP (Chemical Mechanical Polishing) has been established for polishing Si wafers and the like, and it is desirable because it can produce extremely excellent surface smoothness. However, lapping used for polishing glasses lenses and contact lenses is desirable. There is no particular limitation as long as it is a polishing method capable of producing desired surface smoothness, such as a polishing method using a film and a buffing method used when polishing a metal material.
The surface roughness (Ra) of the upper surface portion of the microchannel protrusion is preferably 0.2 μm or less, more preferably 0.1 μm or less. If the surface roughness (Ra) of the upper surface of the microchannel protrusion exceeds 0.2 μm, the surface of the plastic microchannel to be transferred has the same level of surface property, so detection using an optical system such as a thermal lens microscope May be impossible to detect with the instrument.
A plastic microchannel substrate is manufactured by using the injection mold method, the hot embossing method, and the mold method using the mold thus prepared. The surface roughness (Ra) of the microchannel bottom of the produced plastic microchannel substrate is preferably 0.2 μm or less, more preferably 0.1 μm or less. If the surface roughness (Ra) of the upper surface of the microchannel projection exceeds 0.2 μm, it may be impossible to detect with a detector using an optical system such as a thermal lens microscope.

The plastic material used for the plastic microchannel substrate according to the present invention has low auto-fluorescence because the most currently used detection method, including processability and economy, is fluorescence detection. Cyclic polyolefin (COC), which is recognized as a material that can be contacted without any problem, is most preferable, but various plastic materials can be selected, and the use, processing, and solvent used for the produced macrochip Depending on the characteristics of the physiologically active substance and the detection method, it is appropriately selected in consideration of moldability, heat resistance, chemical resistance, adsorptivity and the like.
For example, polystyrene, polyethylene, polyvinyl chloride, polypropylene, polycarbonate, polyester, polymethyl methacrylate, polyvinyl acetate, vinyl-acetate copolymer, styrene-methyl methacrylate copolymer, acrylonitrile-styrene copolymer, acrylonitrile- Examples include butadiene-styrene copolymer, nylon, polymethylpentene, silicone resin, amino resin, polysulfone, polyethersulfone, polyetherimide, fluororesin, and polyimide.
In addition, additives such as pigments, dyes, antioxidants, and flame retardants may be appropriately mixed with these plastic materials.

  The microchannel preferably has a width of 1 mm or less, more preferably 800 μm or less, and a depth from the viewpoint of increasing the amount of sample or reagent used or the amount of discharged waste liquid and increasing the speed of heat transfer / mass transfer. 1 mm or less is preferable, More preferably, it is 800 micrometers or less. However, the flow path design of these microchannels is not limited to the above because it is appropriately designed in consideration of the detection object and convenience. In addition, the microchannel function is equipped with microdevices, specifically, membranes, pumps, valves, sensors, motors, mixers, gears, clutches, microlenses, electrical circuits, etc. It can be compounded by processing on top.

A physiologically active substance can be immobilized on a part of the microchannel of the plastic microchip substrate. Examples of the physiologically active substance include nucleic acids, proteins, sugar chains, glycoproteins and the like, and an optimal physiologically active substance can be appropriately selected depending on the characteristics of the detection target. A plurality of physiologically active substances may be immobilized on the same channel, or different microchannels may be formed on the same microchip substrate and the physiologically active substances may be separately immobilized. In order to immobilize a physiologically active substance on a plastic microchannel substrate, surface modification is performed on the plastic surface, for example, introduction of functional groups, immobilization of functional materials, imparting hydrophilicity, imparting hydrophobicity, etc. It is also possible.

    EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Example 1
A microchannel portion 12 having a width of 800 μm, a length of 50 mm, and a depth of 100 μm and a dummy having a width of 3000 μm, a length of 50 mm, and a depth of 120 μm are formed on an acrylic resin substrate having a length of 70 mm, a width of 30 mm, and a thickness of 1 mm. The part 11 was formed by a cutting method. The cutting conditions were as follows. An end mill with a microchannel portion of 800 μm width was used, an end mill rotation speed of 15000 rpm, a feed rate of 0.5 mm / second, a cutting depth pitch of 50 μm, and a dummy portion with an end mill width of 3000 μm. The rotation speed of the end mill was 15000 rpm, the feed rate was 0.5 mm / second, and the pitch of the cutting depth was 60 μm. Cutting was performed with pure water constantly flowing on the substrate in order to discharge cutting powder during cutting. The surface roughness (Ra) of the bottom of the acrylic microchannel obtained was 0.35 μm. Gold (Au) is vapor-deposited on the acrylic microchannel, and then electroformed with a Watt's electroforming liquid (Ni electroforming liquid) at a current density of 20 mA / cm ² for 10 days, and nickel (Ni ) A mold was obtained. The surface roughness (Ra) of the upper portion of the microchannel portion of the nickel (Ni) mold was measured and found to be 0.35 μm. When polishing was performed with 6 μm alumina particles for 3 hours and 3 μm alumina particles for 3 hours with a CMP (Chemical Mechanical Polishing) polishing apparatus, the surface roughness Ra of the upper surface of the microchannel-shaped protrusion was 0.04 μm. . Using this nickel (Ni) mold, a microchannel substrate made of saturated cyclic polyolefin (COC) was produced by an injection molding method. When the surface roughness (Ra) of the bottom part of the produced plastic microchannel was measured, it was 0.03 μm. When the detection sensitivity was confirmed on the microchannel substrate using a thermal lens microscope, a good focus was obtained.

(Example 2)
A nickel (Ni) disk having a thickness of 15 mm and a diameter of 100 mm was spin-coated with SU-8 2075 photoresist (manufactured by Nippon Kayaku Microchem) at a thickness of 150 μm and prebaked in an oven. After pre-baking, a microchannel portion 12 having a width of 100 μm, a length of 50 mm, and a depth of 100 μm and a dummy portion 11 having a width of 3000 μm, a length of 50 mm, and a depth of 120 μm as shown in FIG. Pattern exposure was performed at a dose of. After the exposure, post-baking was performed, and the film was developed by dipping in a developer. Electrodes are attached to a Ni disk having a microchannel patterned photoresist on its surface, and electroformed for 15 hours at a current density of 10 mA / cm ² using Watt's electroforming liquid (Ni electroforming liquid). Then, a 125 μm-thick Ni electroformed projection was formed on the Ni disk, and the remaining photoresist was all removed with a developer. The surface roughness Ra of the upper surface of the microchannel protrusion was measured and found to be 0.28 μm. When polishing was performed with 6 μm alumina particles for 3 hours and 3 μm alumina particles for 3 hours with a CMP (Chemical Mechanical Polishing) polishing apparatus, the surface roughness Ra of the upper surface of the microchannel-shaped protrusion was 0.04 μm. . Using this nickel (Ni) mold, a microchannel substrate made of saturated cyclic polyolefin (COC) was produced by an injection molding method. The surface roughness (Ra) of the bottom of the produced plastic microchannel was measured and found to be 0.02 μm. When the detection sensitivity was confirmed on the microchannel substrate using a thermal lens microscope, a good focus was obtained.

(Example 3)
A stainless steel (SUS) disk having a thickness of 15 mm and a diameter of 100 mm was spin-coated with SU-8 2075 photoresist (manufactured by Nippon Kayaku Chem) at a thickness of 180 μm and prebaked in an oven. After pre-baking, a microchannel portion 12 having a width of 800 μm, a length of 50 mm, and a depth of 100 μm and a dummy portion 11 having a width of 3000 μm, a length of 50 mm, and a depth of 120 μm as shown in FIG. Pattern exposure was performed at a dose of. After the exposure, post-baking was performed, and the film was developed by dipping in a developer. An electrode is attached to a Ni disk having a microchannel patterned photoresist on the surface, and electroforming for 15 hours at a current density of 15 mA / cm ² using Watt's electroforming liquid (Ni electroforming liquid). Then, a 150 μm-thick Ni electroformed protrusion was formed on the SUS disk, and the remaining photoresist was all removed with a developer. The surface roughness Ra of the upper surface of the microchannel protrusion was measured and found to be 0.32 μm. When polishing was performed with a polishing film in which 3 μm alumina particles were fixed to a plastic film, the surface roughness Ra of the upper surface of the microchannel-shaped protrusion was 0.08 μm. Using this nickel (Ni) mold, a microchannel substrate made of polymethylmethacrylate (PMMA) plastic was produced by hot embossing. The surface roughness (Ra) of the bottom of the produced plastic microchannel was measured and found to be 0.05 μm. When the detection sensitivity was confirmed on the microchannel substrate using a thermal lens microscope, a good focus was obtained.

(Comparative Example 1)
A microchannel having a width of 800 μm, a length of 50 mm, and a depth of 100 μm was formed by a cutting method on an acrylic resin substrate having a length of 70 mm, a width of 30 mm, and a thickness of 1 mm. The cutting conditions were as follows: an end mill with a width of 800 μm was used, the rotation speed of the end mill was 15000 rpm, the feed rate was 0.5 mm / second, and the pitch of the cutting depth was 50 μm. Cutting was performed with pure water constantly flowing on the substrate in order to discharge cutting powder during cutting. The surface roughness (Ra) of the bottom of the acrylic microchannel obtained was 0.35 μm. Gold (Au) is vapor-deposited on the acrylic microchannel, and then electroformed with a Watt's electroforming liquid (Ni electroforming liquid) at a current density of 20 mA / cm ² for 10 days, and nickel (Ni ) A mold was obtained. The surface roughness (Ra) of the upper portion of the microchannel portion of the nickel (Ni) mold was measured and found to be 0.35 μm. When this mold was used to produce a plastic microchannel substrate by injection molding, the surface roughness (Ra) of the plastic microchannel bottom was 0.33 μm. When the detection sensitivity was confirmed on the microchannel substrate using a thermal lens microscope, the focus was not obtained, and it was found that the microchannel substrate could not be used for a measurement application using the thermal lens microscope.

(Comparative Example 2)
A nickel (Ni) disk having a thickness of 15 mm and a diameter of 100 mm was spin-coated with SU-8 2075 photoresist (manufactured by Nippon Kayaku Microchem) at a thickness of 150 μm and prebaked in an oven. After pre-baking, the film was exposed to a microchannel shape of 100 μm width × 50 mm length with a parallel light exposure machine at an irradiation amount of 300 mJ in terms of i-line. After the exposure, post-baking was performed, and the film was developed by dipping in a developer. Electrodes are attached to a Ni disk having a microchannel patterned photoresist on its surface, and electroformed for 15 hours at a current density of 10 mA / cm ² using Watt's electroforming liquid (Ni electroforming liquid). Then, a 125 μm-thick Ni electroformed projection was formed on the Ni disk, and the photoresist was all removed with a developer. The surface roughness Ra of the upper surface of the microchannel protrusion was measured and found to be 0.28 μm. Using this nickel (Ni) mold, a microchannel substrate made of saturated cyclic polyolefin (COC) was produced by an injection molding method. The surface roughness (Ra) of the bottom of the produced plastic microchannel was measured and found to be 0.25 μm. When the detection sensitivity was confirmed on the microchannel substrate using a thermal lens microscope, the focus was not obtained, and it was found that the microchannel substrate could not be used for a measurement application using the thermal lens microscope.

(Comparative Example 3)
A nickel (Ni) disk having a thickness of 15 mm and a diameter of 100 mm was spin-coated with SU-8 2075 photoresist (manufactured by Nippon Kayaku Chem) at a thickness of 180 μm and prebaked in an oven. After pre-baking, the film was exposed to a microchannel shape of 800 μm width × 50 mm length with a parallel light exposure machine at an irradiation amount of 330 mJ in terms of i-line. After the exposure, post-baking was performed, and the film was developed by dipping in a developer. An electrode is attached to a Ni disk having a microchannel patterned photoresist on the surface, and electroforming for 15 hours at a current density of 15 mA / cm ² using Watt's electroforming liquid (Ni electroforming liquid). Then, a 150 μm thick Ni electroformed projection was formed on the Ni disk, and the photoresist was completely peeled off with a developer to obtain a nickel (Ni) mold. The surface roughness Ra of the upper surface of the microchannel protrusion was measured and found to be 0.32 μm. When polishing was performed with 6 μm alumina particles for 3 hours and 3 μm alumina particles for 3 hours with a CMP (Chemical Mechanical Polishing) polishing apparatus, the microchannel protrusions were deformed and partly lost and could not be used as a mold. It became a state.

  By using the production method of the present invention, a mold having microchannel-like protrusions with excellent surface smoothness can be produced, and further using this mold, the bottom of the microchannel has a very high surface smoothness, and a liquid It is possible to fabricate a high-performance microchannel substrate that does not have any problem in the flow of liquid and detection of trace substances.

It is the cross-sectional schematic which becomes one Example of the manufacturing method of the casting_mold | template for microchannel board | substrate manufacture of this invention. It is the cross-sectional schematic which becomes the other Example of the manufacturing method of the casting_mold | template for microchannel board | substrate preparation of this invention. It is the schematic which becomes one Example of the pattern of the microchannel part of this invention, and a dummy part.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Original plate 2 Mold body electroformed and transferred from original plate 3 Microchannel electroformed portion 4 Dummy electroformed portion 5 Metal substrate 6 Photoresist 7 Microchannel portion photoresist pattern (development portion)
8 Dummy part photoresist pattern (development part)
9 Microchannel electroformed part 10 Dummy electroformed part 11 Dummy pattern part 12 Microchannel pattern part

Claims (10)

A method for producing a mold for producing a microchannel substrate having a metal projection for forming a microchannel having a width of 1 mm or less and a height of 1 mm or less on a metal substrate,
(1) A step of forming a macro channel projection and a dummy projection on a metal substrate ,
The process in which the height of the dummy protrusion is greater than the height of the microchannel protrusion
(2) and a step of polishing the upper surface portion of the microchannel-like protrusion and the upper surface of the dummy protrusion,
Only including,
Forming a macro-channel-shaped protrusion and a dummy protrusion on the metal substrate;
(A) A step of etching or cutting a silicon substrate, a glass substrate, or a plastic substrate to produce an original plate,
(B) and a process of electroforming metal on the original plate
Or
(C) a step of coating a photoresist on a metal substrate;
(D) patterning a photoresist by photolithography,
(E) and a step of electroforming metal on the patterned portion,
A method for producing a mold for producing a microchannel substrate, wherein The microchannel protrusions and a method for manufacturing a microchannel substrate fabrication mold of claim first, wherein dummy protrusions is a metal containing nickel. Wherein the metal substrate is a method for manufacturing a microchannel substrate manufacturing mold according to any one of claims 1 or 2 and a metal containing nickel. In the step of polishing the upper surface portion of the microchannel-like protrusion and the upper surface of the dummy protrusion,
The method for producing a mold for producing a microchannel substrate according to any one of claims 1 to 3 , comprising a step of polishing by a CMP (Chemical Mechanical Polishing) method. The method for producing a template for producing a microchannel substrate according to any one of claims 1 to 4, wherein the surface roughness (Ra) of the upper surface portion of the metal projection for forming the microchannel is 0.2 µm or less. Claim 1-5 microchannel substrate fabrication molds produced by the method for manufacturing a microchannel substrate fabrication mold of any one. A plastic microchip substrate, wherein a microchannel is formed on a plastic substrate using the mold for producing a microchannel substrate according to claim 6 . The plastic microchip substrate according to claim 7, wherein the surface roughness (Ra) of the bottom of the microchannel is 0.2 μm or less. The plastic microchip substrate according to claim 7 or 8, wherein the plastic substrate is composed of a saturated cyclic polyolefin. A microchip substrate in which a physiologically active substance containing at least one of nucleic acid, protein, sugar chain, and glycoprotein is immobilized on a part of a microchannel of the plastic microchip substrate according to any one of claims 7 to 9 .

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