JP2006258508A - Bonding method of plastic member, and biochip and micro analysis chip manufactured using method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a process for laminating a plastic biochip or a micro analysis chip firmly at a low temperature, and the plastic biochip or the micro analysis chip laminated thereby. <P>SOLUTION: This bonding method of plastic members, which is a bonding method of two or more board-like plastic members, has characteristics wherein a fine circuit is formed on the bonding surface side of at least one board-like plastic member, and a projection-shaped portion is formed on a part of on the bonding surface of at least one board-like plastic member, and bonding is performed by deformation of the projection-shaped portion at the bonding time. The method also has a characteristic wherein, preferably, the bonding method is one or a composite method between a laser bonding, bonding by overheating and ultrasonic bonding. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for satisfactorily bonding a plastic biochip or microanalysis chip, and relates to a plastic biochip or microanalysis chip obtained by using the method.

  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, plastic biochips or microanalytical chips still have many technical drawbacks and have not gained recognition to replace glass. In particular, the biochip or microanalysis chip collectively called microfluidics is an analysis chip characterized by a micro flow path provided inside the chip. There are many drawbacks, and it is still in the research stage. The problem with plastic microfluidics is that it is necessary to attach another plastic plate on a plastic plate that has been processed into a fine flow path, and to cover the fine flow path.・ The fact that a simple and reliable method has not yet been found is considered to be one of the major factors hindering its practical application.

  In the bonding process for plastic biochips or microanalysis chips, bonding is mainly performed by using an adhesive or by thermocompression bonding with heating, ultrasonic waves, or laser (see Patent Document 1). However, the use of an adhesive tends to cause an excess portion between the substrates, and the microchannel is likely to be blocked or the inner wall is contaminated. The fusion by heating is likely to cause a deactivation problem of the physiologically active substance due to overheating described later. Although heat welding by ultrasonic waves can join surfaces of several millimeters square, it is unsuitable for heat welding of surfaces of several centimeters square, and insufficient welding tends to occur. With laser irradiation, it is very difficult to overheat only the central part of the plastic, such as the two plastic bonding surfaces, regardless of the irradiated surface, and it is not practical at this time.

  Furthermore, if you look at the sticking of plastic products regardless of biochips or microanalysis chips, as a joining method other than the above, you can make a protrusion on the part of the joining surface of the part you are going to join, There is a proposal of a method in which a part is bonded to another surface to be joined and the part is thermally fused by ultrasonic vibration (see Patent Document 2). However, this method can be used only for relatively small molded products that are not very fine, and the method is not intended for biochips and microanalysis chips having a fine structure.

  In addition, when considering application to analysis chips, particularly biochips, various substances such as nucleic acids, proteins, antibodies, sugar chains, glycoproteins, and aptamers are often coated or immobilized on detection sites. Since these physiologically active substances are vulnerable to heating and can be chemically deactivated, the bonding process exposed to high temperatures is unsuitable for the production of biochips and microanalytical chips. From the above, there has not yet been found a technique that can completely bond contact surfaces at a relatively low temperature and can be used for bonding plastic biochips and microanalysis chips. For the practical application of plastic biochips and microanalytical chips, low temperature bonding technology is considered to be more important.

JP 2002-139419 A JP-A-5-16241

  The present invention provides a process for bonding plastic biochips and microanalysis chips at a relatively low temperature, inexpensively, simply, and firmly, and further, the plastic biochips and microanalysis bonded thereby. The purpose is to provide a chip.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have provided a protrusion on a part of a portion that is assumed to be bonded, and undergoes a process of deforming it at the time of bonding, at a relatively low temperature, It has been found that it can be quickly laminated with sufficient bond strength. Moreover, it was confirmed that a plastic biochip and a plastic microanalysis chip processed using the same could be realized, and the present invention was achieved.

That is, the present invention
(1) A method for joining two or more plate-like plastic members, wherein a fine circuit is formed on the joining surface side of at least one plate-like plastic member, and at least one plate-like plastic member has A method for joining plastic members, characterized in that a projection-shaped part is formed on a part of the joining surface, and the projection-shaped part is joined when deformed during joining,
(2) In the joining method, any one of laser joining, joining by overheating, ultrasonic joining, or a composite joining method thereof is used, The joining method of plastic members according to (1),
(3) In the deformation of the protrusion-shaped part at the time of joining, when the height of the protrusion-shaped part before joining is 100%, the height of the projecting-shaped part deformed when joining is completed is 50% or less. A method for joining plastic members according to (1) or (2), characterized in that
(4) The method for joining plastic members according to any one of (1) to (3), wherein the material of the protrusion-shaped part is different from the material of the other part,
(5) The method for joining plastic members according to any one of (1) to (4), wherein the protrusion-shaped part is disposed in the vicinity of the fine channel.
(6) A plastic biochip or microanalysis chip, which is bonded using the bonding method according to any one of (1) to (5),
(7) The plastic biochip according to (6), which is at least one selected from a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip,
It is.

  When attaching plastic biochips and microanalysis chips, when resin is joined by heating, proteins and antibodies deactivate their physiological activity by heating, so joining treatment with heating could not be used. Compared with the conventional method, the method of the present invention can be applied at a relatively low temperature of 100 ° C. or less, and is particularly effective as a technology for producing plastic biochips and microanalysis chips.

Hereinafter, embodiments of the present invention will be described in detail.
This patent states that, in a plastic biochip or microanalysis chip, it is possible to bond firmly by providing a protrusion shape on a part of the bonding surface and deforming the protrusion shape in the bonding process. Heading and patenting.

  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, semi-cured phenol resin, This indicates a polymer material having a melting point and Tg, such as a semi-cured epoxy resin and other various thermoplastics, but the type, polymerization degree, physical properties such as melting point, Tg, and elastic modulus are particularly limited. It is not a thing.

  This patent is based on the premise that two or more plastics are joined. However, it is considered that the processing method is not limited to plastics but can be joined with plastics and non-plastics. Non-plastic here refers to copper, aluminum, iron, silicon, nickel and other various metals and alloys thereof, metal oxides such as silica, alumina, zirconia, titania, mixtures thereof, glass materials thereof, Various ceramics such as silicon carbide and boron nitride, linear wiring and foil-shaped wiring and various sensors made of these ceramics, various sensors, and other materials that do not fall under plastics, such as paper and wood, are targeted. Alternatively, fully cured phenolic resins and fully cured epoxy resins also fall into the category.

  The protrusion shape provided in advance on a part of the bonding surface used in the present invention refers to a protrusion-shaped object made of plastic and protruding from the surface of the bonding surface, preferably at a height of 200 μm or less. . The cross-sectional shape may be rectangular, trapezoidal or triangular, and is not particularly limited. When the projection is viewed from above, the overall shape is a point (circle, square, triangle, etc.), line (straight line, curve, dashed line, dot-dot line, etc.), surface (circle, square, triangle, etc.) However, it is not particularly limited. In the case of application to microfluidics, it is more preferable that the protrusions are arranged in parallel / linearly in the vicinity of the fine flow path, so that the protrusions can replace the seal and the liquid passing through the flow path is difficult to leak. In addition, if the flow path is processed on the surface of the joint surface or there is a complicated uneven shape, the target part is a protrusion or other part is recessed when it has a complicated shape as a whole. It may be difficult to determine whether or not you are just going. In this case, the height that occupies the majority of the area to be joined is set as a standard, and a portion that is more convex than that is determined as a protrusion.

  The protrusion in the present invention is characterized in that it is crushed during bonding. By applying energy from the outside only to the protrusions in some way, the tip or the entire protrusion is deformed by melting or dissolving, and as a result, the molecular motion of the plastic forming the protrusions becomes active and finally Can be bonded well to the object to be bonded. And even if a projection part deform | transforms, it is the characteristics that another site | part does not heat and does not deform | transform. The degree of collapse of the protrusion is not particularly limited, but when the height of the original protrusion is 100%, the height of the protrusion deformed upon completion of bonding is desirably 95% or less, and more preferably 50%. The following is more desirable for improving the bonding strength. Further, there is no problem even if the composition of the protrusions is different from the composition of other parts. It is considered more preferable to appropriately select a material having flexibility, melting point, heat distortion temperature, and melt viscosity more optimal for bonding.

  The joining method in the present invention is not particularly limited. As an example, bonding by an adhesive, ultrasonic bonding, vibration bonding, laser bonding, solvent bonding, bonding by overheating, and the like can be used. A processing method that enables heating / melting of only the protrusions in a concentrated manner, such as laser or ultrasonic waves, or joining by overheating using a spot heater that can heat only a minute region is more preferably used. The

  Using the plastic bonding method of the present invention, a relatively large area can be bonded firmly and without contamination in a relatively low-temperature process, and a plastic biochip or microanalysis chip with good performance can be manufactured at low cost. is there. In particular, it can be suitably used for products subjected to fine processing such as microfluidics. In particular, a product group in which a physiologically active substance such as a nucleic acid chip, protein chip, antibody chip, aptamer chip, glycoprotein chip, etc. is immobilized on the surface or inside of the chip can be mentioned.

  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 molded product having the shape shown in FIG. 1 using acrylic as a raw material was obtained by molding and cutting. This molded product has a through-hole 1 (diameter 1 mm), a micro-channel 2 (length 25 mm, a cross-sectional shape is rectangular, a depth 100 μm, a width 200 μm), and a projection 3 (material is acrylic, height is the same as other parts) 50 μm, width 20 μm, cross-sectional shape is rectangular, and is installed at a location 40 μm away from the microchannel and through-hole).
Moreover, the resin plate shown in FIG. 2 was obtained by molding using acrylic as a raw material. The molded product shown in FIG. 2 is placed on the processed surface A of the molded product shown in FIG. 1, the horn of the ultrasonic welder is placed on the molded product 2 and a weight of 30 kg is applied, and the frequency is 20 kHz and the amplitude is 80 μm. The vibration direction was joined by applying ultrasonic vibration in a direction parallel to the surface for 1 second. The protrusion having a height of 50 μm was crushed to a height of 5 μm, but the two resin plates were joined. The bond was strong and did not peel off when twisted by hand. The microchannel portion was 200 μm wide and 100 μm deep as originally designed, and no deformation or the like was observed. Although water was allowed to flow through the fine channel portion, water did not flow outside the channel, and it was confirmed that the microfluidics can be used without any problem.

(Example 2)
A molded product having a shape shown in FIG. 3 was obtained by cutting using a polyvinyl chloride (heat deformation temperature 60 ° C.) in which black pigment was dissolved and an acrylic plate (heat deformation temperature 100 ° C.) coated on the surface. . This molded product has a through-hole 21 (diameter 1 mm), a micro-channel 22 (length 25 mm, a cross-sectional shape is rectangular, a depth 100 μm, a width 200 μm), and a projection 23 (the material is a poly-polysiloxane having a black pigment dissolved therein) Vinyl chloride, height 40 μm, width 100 μm, cross-sectional shape is rectangular, installed at a location 300 μm away from the microchannel and through-hole). Moreover, the resin plate shown in FIG. 2 was obtained by molding using acrylic as a raw material. The molded product of FIG. 2 is placed on the processed surface A of the molded product of FIG. 3, and a YAG laser processing machine is used to irradiate a YAG laser with a wavelength of 1064 nm and an output of 10 W by applying a weight of 30 kg. Only the projections of the polyvinyl chloride were melted and joined. The protrusion having a height of 40 μm was crushed to a height of 5 μm, but the two resin plates were joined. The bond was strong and did not peel off when twisted by hand. The microchannel portion was 200 μm wide and 100 μm deep as originally designed, and no deformation or the like was observed. Although water was allowed to flow through the fine channel portion, water did not flow outside the channel, and it was confirmed that the microfluidics can be used without any problem.

(Example 3)
A molded product having the shape shown in FIG. 4 using acrylic as a raw material was obtained by molding and cutting. This molded product has a through-hole 31 (diameter 1 mm), a micro-channel 32 (length 25 mm, a cross-sectional shape is a rectangle, a depth 100 μm, a width 200 μm), and a protrusion 33 (the material is acrylic, height is the same as other parts) 50 μm, width 20 μm, the cross-sectional shape is rectangular, and is provided at a location 40 μm away from the microchannel and the through-hole) and the projection 34 (material is acrylic, diameter 1 mm, height 850 μm as in other locations). A resin plate shown in FIG. 5 was obtained by molding using acrylic as a raw material. This molded product has a through-hole 41 (diameter 1 mm, provided at a position where 34 protrusions in FIG. 4 are inserted). 5 is placed on the processing surface A of the molded product of FIG. 1 and the projection 34 of FIG. 4 is inserted into the through hole 41 of FIG. Bonding was performed under the same conditions. With respect to the protrusion 33 in FIG. 4, the protrusion having a height of 50 μm was crushed to a height of 5 μm, and for the protrusion 34 in FIG. 4, the protrusion having a height of 850 μm was crushed to a height of 810 to 800 μm. The resin plates were firmly joined. The microchannel portion was 200 μm wide and 100 μm deep as originally designed, and no deformation or the like was observed. Although water was allowed to flow through the microchannel, it was confirmed that water could not flow outside the channel and could be used without any problems as a microfluidic.

(Comparative Example 1)
Using acrylic as a raw material, the molded product having the shape shown in FIG. 6 was obtained by molding and cutting. This molded product has a through-hole 51 (diameter 1 mm) and a micro-channel 52 (length 25 mm, cross-sectional shape is rectangular, depth 100 μm, width 200 μm). Experiments were performed to join the molded products of FIGS. 6 and 2 under the same conditions as in Example 1. FIG. However, the molded product of FIG. 6 having no protrusion shape and the molded product of FIG. 2 could not be joined, and microfluidics could not be obtained.

(Comparative Example 2)
A joining experiment was conducted in the same manner as in Comparative Example 1. In addition, the weight of the ultrasonic horn was set to 200 kg, and the ultrasonic application time was set to 20 seconds. However, the molded product of FIG. 6 having no protrusion shape and the molded product of FIG. 2 could not be joined, and microfluidics could not be obtained.

(Comparative Example 3)
Using acrylic as a raw material, the molded product having the shape shown in FIG. 6 was obtained by molding and cutting. Further, a molded product having the shape shown in FIG. 2 was obtained by molding using acrylic as a raw material. The molded product of FIG. 2 is placed on the processed surface A of the molded product of FIG. 6 and heated to 120 ° C. for 30 minutes in a state where a weight of 50 kg is applied. A joined product of the molded product was obtained. Bonding was extremely strong. Although it was gradually cooled after the completion of joining, the entire molded product was warped thereafter. Although water was allowed to flow through the fine channel portion, water did not flow outside the channel. However, the initial design of the fine channel part is 200 μm wide and 100 μm deep, but after the bonding process, it is deformed to 240 μm wide and 70 μm deep, and a high temperature is applied to the entire channel. It has been suggested. It has been found that there is a problem in producing a biochip or microanalysis chip by this processing method due to warpage of the entire chip and deformation of the flow path due to heating of the entire flow path.

It is a schematic diagram of a plane and a cross section showing a microfabricated molded product in Example 1. It is a schematic diagram of the plane and cross section which show the molded article in Examples 1, 2 and Comparative Examples 1-3. It is a schematic diagram of a plane and a cross section showing a microfabricated molded article in Example 2. It is the schematic diagram of the plane and cross section which show the microfabrication molded product in Example 3. FIG. It is a schematic diagram of a plane and a section showing a molded product in Example 3. It is a schematic diagram of the plane and cross section which show the microfabrication molded product in Comparative Examples 1-3.

Explanation of symbols

1, 21, 31, 41, 51 through holes,
2, 22, 32, 52 microchannel,
3, 23, 33, 34 Projection

Claims (7)

A method of joining two or more plate-like plastic members, wherein a fine circuit is formed on the joining surface side of at least one plate-like plastic member, and the joining surface of at least one plate-like plastic member is A method for joining plastic members, characterized in that a protrusion-shaped part is formed in a part, and the protrusion-shaped part is joined by deformation at the time of joining. 2. The method for joining plastic members according to claim 1, wherein any one of laser joining, joining by overheating, ultrasonic joining, or a composite joining method thereof is used as the joining method. In the deformation of the protrusion-shaped part at the time of joining, when the height of the protrusion-shaped part before joining is 100%, the height of the protrusion-shaped part deformed at the completion of joining is 50% or less. The method for joining plastic members according to claim 1 or 2. The method for joining plastic members according to any one of claims 1 to 3, wherein the material of the protrusion-shaped part is different from the material of the other part. The method for joining plastic members according to any one of claims 1 to 4, wherein the protrusion-shaped portion is disposed in the vicinity of the fine flow path. A plastic biochip or microanalysis chip, which is bonded using the bonding method according to claim 1. The plastic biochip according to claim 6, which is at least one selected from a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip.

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