JP2007283437A - Micro-passage forming method to plastics, and plastic biochip or micro-analysis chip manufactured by using the method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a high-performance plastic biochip or micro-analysis chip, having high smoothness of a micro-passage, and having no problem in flowing of a liquid and detecting a very small quantity of material. <P>SOLUTION: In this method of forming a micro-structure such as a micro-passage 1 mm or less wide and 1 mm or less deep on the surface made of plastics, cutting is performed using an end mill having an end cutting edge flat, that is, an end cutting edge whose radial concave angle of 0°. The plastic product is obtained by the above method. This biochip or micro-analysis chip is formed of the plastic product. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a method for forming a smooth and fine micro-channel in plastic, and further relates to a plastic product manufactured using the method, particularly a plastic biochip or a microanalysis chip.

  In recent years, biochips, which are devices in which a physiologically active substance is immobilized on a solid substrate, have attracted attention as means for achieving high throughput in drug discovery research and clinical tests. Typical examples of the physiologically active substance to be immobilized include nucleic acids, proteins, antibodies, sugar chains, glycoproteins, aptamers, etc. Nucleic acid microarrays, which are biochips on which nucleic acids are immobilized, are already available in many products. It is on the market. The form of the chip is a form in which various physiologically active substances are spotted and immobilized on a flat substrate, and are mainly used for research analysis in research institutions.

  In recent years, research on miniaturization of chemical reaction, separation, and analysis system using microfabrication technology called micro analysis chip, μTAS (micro total analytical system), or lab-on-chip has become active. Various chemical reactions, particularly physiological reactions, can be performed on the (fine channel). In this system, since a very small amount of sample can be analyzed quickly, it is expected to be commercialized as a next-generation biochip that takes advantage of this feature, particularly as a diagnostic biochip in a medical institution ( Hereinafter, these systems are referred to as micro-analysis chips).

  Currently, these biochips and microanalysis chips are mainly made of glass. In order to produce a micro-analysis chip with a glass substrate, for example, there is a method in which a substrate is coated with a metal or a photoresist resin, and a microchannel pattern is baked, followed by an etching process. However, glass is not suitable for mass production and is very expensive, and plasticization is desired.

  Plastic biochips and microanalysis chips can be manufactured by various molding methods such as injection molding using various plastics, and efficient and economical chip manufacturing is possible. It is suitable. However, the disadvantage is that it is not suitable for small-scale production. This is because for injection molding, molding is not possible unless a mold is prepared. The most important problem with plastic products is that it is generally difficult to make a mold with a fine part such as a microchannel, and the smoothness and accuracy of the mold surface cannot be kept high enough. Can be mentioned.

  Next, in the case of producing a small amount of various types of plastic products, a commonly used method is cutting, but plastic has a low softening point and is easy to melt cutting chips. There is a problem that it does not finish cleanly. In addition, microfabrication for biochips and microanalysis chips is usually a process of creating a flow path or the like so as to form a recessed portion, and it is technically necessary to polish the bottom surface of this flow path with a normal polishing apparatus or the like. Is quite difficult. In order to solve the problem, there is a method of devising the shape of a cutting jig such as an end mill (Patent Document 1). However, when the processing size is reduced, the above problem becomes significant and is used for a biochip or a microchemical chip. When the microchannel is formed by cutting, the machined surface is often very dirty, and the optimum machining condition cannot be found or often takes time to find out. In particular, as a problem in the cutting process, there is a tool mark that is generated when a cutting process using a rotating tooth such as an end mill is performed. A tool mark is a trace of a drill. During processing, very fine and regular irregularities may occur on the processed surface, which may hinder optical analysis in biochips and microchemical chips. Of course, if the unevenness is extremely fine, there is often no problem at all, but in many cases the unevenness is large and often hinders optical analysis. In other words, the cutting process is suitable for the production of a small variety of products, but there is a problem that the machining accuracy is insufficient in the processing of the micro flow path which is the subject of this patent. From the above, when trying to obtain a plastic micro-channel, the current molding and cutting, or a combination of both, is insufficient in terms of processing accuracy, especially the surface smoothness of the channel is insufficient. In many cases, it does not meet market demands.

JP 2002-210609 A

  The present invention relates to a feature when a micro-channel is formed on a plastic surface by cutting, and relates to a method for realizing it, and a plastic biochip and a micro-analysis chip using the same are prepared and provided. It is intended to do.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have found that the tool mark is extremely sharp by cutting using an end mill having a bottom blade flat, that is, a bottom blade having a radial angle of 0 °. The present inventors have found that a plastic micro-channel can be made that is small, smooth and good in accuracy, and has led to the present invention.

That is, the present invention is as follows.
(1) In a method of forming a fine structure such as a microchannel having a width of 1 mm or less and a depth of 1 mm or less on a surface made of plastic, a bottom blade flat, that is, a bottom blade with a radial angle of 0 ° is provided. A method of forming a micro flow path in a plastic, characterized by cutting using an end mill.
(2) A plastic product having the microchannel formed by the microchannel formation method according to (1).
(3) The plastic product according to (2), wherein Ra of the surface smoothness of the bottom surface of the microchannel is 0.1 μm or less.
(4) The plastic product according to (2) or (3), wherein Ry of the surface smoothness of the bottom surface of the microchannel is 1 μm or less.
(5) The plastic product according to any one of (2) to (4), wherein there is no tool mark on the bottom surface of the microchannel.
(6) A biochip or microanalysis chip comprising the plastic product according to any one of (2) to (5).
(7) A mold for plastic molding produced by electroforming using the plastic product according to any one of (2) to (5) as a mold.
(8) A method for producing a plastic product, which is molded by injection molding or hot embossing using the plastic molding die according to (7).
(9) A plastic biochip or microanalysis chip obtained by the method for producing a plastic product according to (8).
(10) The plastic biochip according to (6) or (9), which is at least one selected from a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip.
(11) The plastic biochip according to (6) or (9), which is at least one selected from a chip for chemical analysis, a chip for environmental analysis, and a chip for chemical synthesis.

When producing a plastic biochip or microanalysis chip having a fine flow path, the smoothness of the flow path obtained by using the production method of the present invention compared to the conventional method is very high, and the liquid Therefore, it is possible to create a high-performance microchannel without any problem in the flow of liquid and detection of trace substances. Furthermore, it is possible to provide high-performance biochips and microanalysis chips at low cost.

Hereinafter, embodiments of the present invention will be described in detail.
The present invention is characterized in that, in a micro flow path formed by cutting plastic, cutting is performed using an end mill having a bottom blade flat, that is, a bottom blade having a radial angle of 0 °. Furthermore, the present invention relates to a plastic product produced by the method, in particular, a biochip and a micro analysis chip.
The microchannel in the present invention refers to a groove having a width of 1 mm or less and a depth of 1 mm or less. There are no particular limitations on the shape, such as the length, bending, and branching of the microchannel. The cross-sectional shape of the groove is not particularly limited. There are no problems with rectangular, triangular, semi-circular, through-holes, or a composite of them. However, for the purpose of optical detection, in some or all of the channels, there is a bottom surface of the channel that is parallel to the substrate surface, such as rectangular, trapezoidal, semicircular or elliptical, and their composite shapes. It is necessary that a cross-sectional shape exists.

  Examples of the plastic used in the present invention include high-density polyethylene, low-density polyethylene, polypropylene, polystyrene, various cyclic polyolefins, polymethyl methacrylate, polynorbornene, polyphenylene oxide, polycarbonate, polyamide, polyester, polytetrafluoroethylene, and various silicones. Resin, semi-cured or fully cured phenolic resin, semi-cured or fully cured epoxy resin, and other various thermoplastic or thermosetting plastics in general. It does not specifically limit regarding physical properties, such as a kind of plastic, a polymerization degree, melting | fusing point, Tg, an elasticity modulus, the light transmittance, and gas barrier property. There is no problem with a composite of a plurality of plastics. Further, there is no problem even if a metal, metal oxide, various inorganic substances, physiologically active substances, various oily substances, etc. are mixed / applied / adhered / embedded on the surface or inside of the plastic.

  The flow path machining process used in the present invention mainly targets cutting by various end mills. The cutting process is not particularly limited as long as the plastic surface is cut by mechanical processing. Moreover, if it is a mechanical cutting process, it will not specifically limit regarding the kind of process, the detail of an apparatus, the shape of a jig for cutting, a material, and a surface state. Furthermore, it is also possible to transfer a plastic cut product to a mold using nickel electroforming, etc., and then mold using injection molding or hot embossing molding using the mold. It is judged to be within the range. There are no limitations on molding conditions such as molding temperature, pressurization pressure, mold smoothness and shape. In addition, various photofabrication such as processing steps using a thick resist such as SU-8, processing steps using silicon etching, and LIGA are not included in the scope of claims of this patent.

  The tool mark in the present invention is fine and periodic unevenness generated by cutting. The tool mark can be observed with a scanning electron microscope, but more precisely, observation and measurement with an AFM are more desirable.

 As a result of evaluating whether or not optical detection is possible by intentionally changing the size of the tool mark existing on the bottom surface of the microchannel when the present inventor performs analysis by an optical method in a biochip or a microchemical chip If the period of the tool mark is less than 1 μm or the height is less than 100 nm, optical detection in the microchannel is possible even if the tool mark exists, and the tool mark itself is very difficult to see and the tool mark is substantially It turns out that it is safe to judge that it does not exist. Microchannels that satisfy the conditions did not find any problems in optical detection, but optical detection becomes extremely difficult when there are tool marks with numerical values exceeding those, and the performance as a biochip or microanalysis chip is remarkable. It was judged to have declined.

  In the present invention, the plastic product obtained by cutting using an end mill having a bottom blade flat, that is, a bottom blade having a radial angle of 0 °, is preferably a biochip or a micro analysis chip. In particular, plastic biochips such as nucleic acid chips, protein chips, antibody chips, aptamer chips, glycoprotein chips, environmental measurement chips, various chemical analysis chips, etc. There is no particular limitation on the above.

  The processing accuracy of the surface in the microchannel obtained by the present invention is preferably 0.1 μm or less in terms of Ra. It is equally desirable that Ry is 1 μm or less. If Ra and Ry exceed the upper limit values, it is not desirable because optical detection / measurement of trace components becomes difficult for the same reason as described in the adverse effect of the tool mark.

  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)
Microchip processing shown in FIG. 1 was performed on an acrylic resin plate (heat distortion temperature 140 ° C.) having a thickness of 30 mm × 70 mm square and a thickness of 1 mm (note that the material of the workpiece is specified in the following examples and comparative examples) If not, all are acrylic.) Here, the microchannel has a length of 45 mm, a width of 0.3 mm, and a depth of 0.2 mm, and the through hole has a diameter of 1 mmφ. The micro-channel was processed using a bottom edge flat end mill prepared by polishing the bottom edge of a square end mill. Cutting conditions were as follows: a non-coated super steel end mill with a diameter of 0.3 mmφ and a non-coated super steel was used and processed at a rotational speed of 20,000 rpm and a scanning speed of 2 mm / sec. If the cutting conditions are not specified, it shall be processed under the above conditions.) The cutting fluid used was a water-soluble cutting oil.

(Example 2)
After the nickel sputter coating having a thickness of 50 nm is applied to the surface of the microchip prepared in Example 1, nickel electroforming is performed in a Barett bath. After processing for 20 hours at an electric current of 45 mA / cm 2, the acrylic resin prototype was dissolved and removed by refluxing chloroform to obtain a nickel micro mold having a thickness of about 1 mm. The obtained mold was bonded to a metal block with a thermosetting adhesive, and the metal block was attached to an injection molding machine to perform injection molding. Cyclic polyolefin was used as the resin used for molding. The molding temperature was 150 ° C. and the mold temperature was 50 ° C. The molded product formed by injection molding was manually runner and deburred to obtain the microchip of FIG.

(Comparative Example 1)
In Example 1, microchannel processing was performed using a commercially available square end mill, and the microchip of FIG. 1 was obtained.

(Evaluation method 1)
The surface roughness of the microchannel obtained in Example 1, Example 2 and Comparative Example 1 was measured using a laser type non-contact surface shape measuring instrument.

(Evaluation method 2)
Using AFM, the presence or absence of periodic unevenness present on the surface of the microchannel obtained in Example 1, Example 2 and Comparative Example 1 was confirmed, and the period and average when periodic unevenness was present Height was measured.

(Evaluation method 3)
A flat sheet of acrylic or cyclic polyolefin having a thickness of 30 mm × 70 mm and a thickness of 0.2 mm was placed on the surface of the processed product obtained in Example 1, Example 2 and Comparative Example 1, and thermocompression bonded by a press. The microchannel portion of the obtained product was filled with water, and measurement was attempted using a thermal lens microscope in that state. Details of the thermal lens microscope are detailed in, for example, Japanese Patent Publication No. 2000-356611. In this evaluation, an argon laser was used as an excitation light source, a helium neon laser was used as a detection light source, and the spot diameter was 1 μm. The sample flowing in the flow path was water, and whether or not the excitation and detection lasers were focused was used as a criterion for this evaluation. There was no problem when the laser focused and there was no problem in measurement, and there was a problem when measurement was difficult because the laser was not focused.

(Evaluation results)
Table 1 shows the microchannel surface roughness (Ra, Ry), AFM measurement results (whether periodic irregularities are present, the period and height of protrusions when they are present), and the measurement results obtained with a thermal lens microscope. Show. The comparative example also has periodic unevenness on the bottom surface of the microchannel, and as a result, it is difficult to measure with a thermal lens microscope. As a result, it was confirmed that measurement with a thermal lens microscope was possible.

The plane model which shows the shape of the components of the micro analysis chip in an Example and a comparative example.

Explanation of symbols

1 Acrylic resin plate or cyclic polyolefin resin plate (30 mm x 70 mm, thickness 1 mm)
2 Micro channel processed by molding or cutting (width 0.3mm, depth 0.2mm, length 40mm)
3 Through hole (diameter 1mmφ) obtained by cutting

Claims (11)

In a method of forming a micro flow path having a width of 1 mm or less and a depth of 1 mm or less on a plastic surface, cutting is performed using an end mill having a bottom blade flat, that is, a bottom blade having a radial angle of 0 °. A method for forming a micro-channel in plastic. The plastic product which has the said micro channel formed by the micro channel formation method of Claim 1. The plastic product according to claim 2, wherein the surface smoothness Ra of the bottom surface of the microchannel is 0.1 μm or less. The plastic product according to claim 2 or 3, wherein the surface smoothness Ry of the bottom surface of the microchannel is 1 µm or less. The plastic product according to any one of claims 2 to 4, wherein there is no tool mark on the bottom surface of the microchannel. A biochip or microanalysis chip comprising the plastic product according to claim 2. A mold for plastic molding produced by electroforming using the plastic product according to claim 2 as a mold. A method for producing a plastic product, which is molded by injection molding or hot embossing using the plastic molding die according to claim 7. A plastic biochip or microanalysis chip obtained by the method for producing a plastic product according to claim 8. The plastic biochip according to claim 6 or 9, which is at least one selected from a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip. The plastic biochip according to claim 6 or 9, which is at least one selected from a chip for chemical analysis, a chip for environmental analysis, and a chip for chemical synthesis.

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