JP2019055379A - Micro flow channel chip, and manufacturing method of the same - Google Patents

Abstract

To enable manufacturing by an easier method, various micro flow channel chips having different functions, and micro flow channel chips having a plurality of functions.SOLUTION: A manufacturing method of a micro flow channel chip 1 including a resin substrate 10 having a flow channel groove 12 on one surface 10a, and a resin film 20 joined to the resin substrate 10 so as to cover the flow channel groove 12 includes: a preparation step of preparing a laminate film 2 which has the resin film 20 and a peeling film 22 stuck to the resin film 20, and has a functional component-containing layer 21 provided between the resin film 20 and the peeling film 22 so as to be peelable from the peeling film 22; a peeling step of peeling the peeling film 22 from the laminate film 2; and a joining step of joining from an exposed surface side, the resin film 20 after the peeling step to the surface 10a on which the flow channel groove 12 in the resin substrate 10 is formed.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a microchannel chip and a manufacturing method thereof.

  In recent years, fine flow paths (micro flow paths) are formed on glass substrates using microfabrication technology, and chemical reactions, separation / analysis, etc. of a small amount of sample are performed in the micro space of the micro flow path. Research on microchannel chips that can be used is underway.

  For example, in International Publication No. 2012/060186 (Patent Document 1), a microchannel including a resin substrate having a channel groove on one surface and a resin film bonded to the resin substrate so as to cover the channel groove. A chip is disclosed. Since this micro-channel chip can be manufactured by joining a resin substrate and a resin film by thermal fusion, the manufacturing cost can be reduced compared to the case of manufacturing a glass substrate or the like. Can do.

  Further, for example, Japanese Patent Application Laid-Open No. 2003-159526 (Patent Document 2) has a function of suppressing the analysis sample from being adsorbed and remaining in the microchannel by configuring the resin substrate with a hydrophilic resin material. A microchannel chip is disclosed.

  According to the method of Patent Document 1, the microchannel chip can be manufactured at a lower cost. However, when a function is to be given to the microchannel of the microchannel chip, a special resin substrate having a desired function has to be prepared as in Patent Document 2 so far. That is, every time a desired function is changed, it is necessary to develop and manufacture a resin substrate having the function from the beginning, resulting in a problem that the manufacturing cost increases. In particular, when a plurality of functions are to be given to one microchannel chip, it has been difficult to realize the conventional method.

International Publication No. 2012/060186 JP 2003-159526 A

  It is desired that various microchannel chips having different functions and microchannel chips having a plurality of functions can be manufactured by a simpler method.

The manufacturing method of the microchannel chip according to the present invention is as follows.
A method of manufacturing a microchannel chip, comprising: a resin substrate having a channel groove on one surface; and a resin film bonded to the resin substrate so as to cover the channel groove,
While having the said resin film and the film for peeling bonded together to the said resin film, it has a functional component content layer provided so that peeling was possible from the said film for peeling between the said resin film and the said film for peeling. A preparation step of preparing a laminated film;
A peeling step of peeling the peeling film from the laminated film;
A bonding step of bonding the resin film after the peeling step from the exposed surface side to the surface of the resin substrate on which the flow channel grooves are formed.

According to this configuration, after peeling off the peeling film from the laminated film to expose the functional component-containing layer, the resin film is joined from the exposed surface side to the surface on which the flow channel groove is formed in the resin substrate. A microchannel chip having a desired function can be manufactured by a simple method.
Therefore, as long as a laminated film having a functional component-containing layer having a desired function is prepared, there is no need to develop and manufacture a special resin substrate as in the prior art, so that the manufacturing cost can be reduced. Furthermore, for example, a plurality of laminated films having functional component-containing layers having different functions are used side by side along the surface of the resin substrate having the flow channel grooves, or a functional component-containing layer having a plurality of different functions. By using a laminated film having a plurality of functions, a plurality of functions can be easily imparted to one microchannel chip.

  Hereinafter, a preferable aspect of the method for manufacturing a microchannel chip according to the present invention will be described. However, the scope of the present invention is not limited by the preferred embodiments described below.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing at least one of a hydrophilic group and a hydrophobic group.

As one aspect,
The functional component-containing layer is a layer containing both a hydrophilic group and a hydrophobic group, and the functional component contains the hydrophilic component and the hydrophobic group according to the flow of fluid in the flow channel. It is mentioned that the content layer is patterned.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing an antistatic agent.

As one aspect,
Examples of the functional component-containing layer include a layer containing any one of a cationic polymer, an anionic polymer, and a zwitterionic polymer.

As one aspect,
It is mentioned that the said functional component content layer is a layer containing a protein low adsorption substance.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing one component involved in specific reaction or specific binding.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing a primer in the polymerase chain reaction.

As one aspect,
In the preparation step, the functional component-containing layer may be patterned by a micro contact printing method.

The microchannel chip according to the present invention is
A resin substrate having a channel groove on one surface;
A resin film bonded to the resin substrate,
The resin film has a functional component-containing layer in a portion covering the flow channel.

  As in this configuration, the functional component-containing layer is exposed in the microchannel including the channel groove by having the functional component-containing layer in the portion covering the channel groove of the resin substrate. A microchannel chip having the above functions can be easily realized. Therefore, according to this configuration, a desired function can be exhibited in the microchannel chip without using a special resin substrate as in the prior art.

  Hereinafter, preferred embodiments of the microchannel chip according to the present invention will be described. However, the scope of the present invention is not limited by the preferred embodiments described below.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing at least one of a hydrophilic group and a hydrophobic group.

As one aspect,
The functional component-containing layer is a layer containing both a hydrophilic group and a hydrophobic group, and the functional component contains the hydrophilic component and the hydrophobic group according to the flow of fluid in the flow channel. It is mentioned that the content layer is patterned.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing an antistatic agent.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing a cationic polymer, an anionic polymer, or a zwitterionic polymer.

As one aspect,
It is mentioned that the said functional component content layer is a layer containing a protein low adsorption substance.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing one component involved in specific reaction or specific binding.

As one aspect,
It is mentioned that the functional component-containing layer is a layer containing a primer in the polymerase chain reaction.

  Further features and advantages of the present invention will become more apparent from the following description of exemplary and non-limiting embodiments described with reference to the drawings.

Cross section of microchannel chip Schematic diagram showing an example of a micro-channel chip manufacturing method

  Embodiments of a microchannel chip and a manufacturing method thereof will be described with reference to the drawings. As shown in FIG. 1, the microchannel chip 1 of this embodiment includes a resin substrate 10 having a channel groove 12 and a resin film 20 bonded to the resin substrate 10. A functional component-containing layer 21 is provided in a portion covering the road groove 12.

  As the resin constituting the resin substrate 10, a resin excellent in heat resistance and transparency can be selected as appropriate. The resin substrate 10 can be made of, for example, a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate.

  The resin substrate 10 has a flow channel 12 on the first surface 10a which is one surface. The number of the channel grooves 12 may be one or plural. When a plurality of flow channel grooves 12 are provided, these flow channel grooves 12 may be provided in series or in parallel. Further, the flow channel 12 may have a branch. For example, the flow channel 12 may have a width of 1 mm or less and a depth of 0.01 mm or more and 0.5 mm or less. In this way, experiments and the like on a minute scale can be performed. A part of the flow channel 12 passes through the resin substrate 10 and opens to the second surface 10b which is the other surface, and the port 14 is formed by the opening.

  The outer shape and size of the resin substrate 10 can be appropriately set in consideration of handling properties, analysis suitability (analysis method and suitability for an analysis apparatus), and the like. For example, in the case of a quadrangle (square or rectangular), for example, the side is preferably 10 mm or more and 200 mm or less, more preferably 10 mm or more and 100 mm or less. The outer shape of the resin substrate 10 may be another polygonal shape, a circular shape, an elliptical shape, or the like.

  The resin substrate 10 may be manufactured by, for example, injection molding, or may be manufactured by cutting the resin substrate 10.

  As the resin constituting the resin film 20, a resin excellent in heat resistance and transparency can be appropriately selected. The resin film 20 can be made of, for example, a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate. The resin constituting the resin film 20 may be the same resin as the resin constituting the resin substrate 10 or may be a different resin.

  Although the thickness of the resin film 20 is not specifically limited, For example, it can be 0.01 mm or more and 1 mm or less. By being 0.01 mm or more, wrinkles and the like are hardly generated at the time of joining, and the flow channel 12 can be sufficiently sealed. Moreover, the favorable followability to the unevenness | corrugation of the resin substrate 10 can be acquired because it is 1 mm or less.

  The resin film 20 has a functional component-containing layer 21 on the first surface 20a that is one surface. The functional component-containing layer 21 is formed, for example, in a state where a predetermined functional component is mixed in an adhesive. As an applicable pressure-sensitive adhesive, the functional component can be retained without losing the function of the functional component, and is peeled off from a peeling film 22 described later while maintaining the adhesive state with the resin film 20. That it is possible is mentioned as a condition. Examples of such an adhesive include acrylic, rubber, silicone, and urethane. In addition, a layer may be formed by directly providing a predetermined functional component itself on the first surface 20a without being mixed in an adhesive or the like.

  Examples of the functional component include a substance having a hydrophilic group, a substance having a hydrophobic group, an antistatic agent, a cationic polymer, an anionic polymer, an amphoteric polymer, a low protein adsorption substance, and a specific reaction. Alternatively, one component involved in specific binding, a primer in the polymerase chain reaction, and the like can be mentioned.

  By including a substance having a hydrophilic group as a functional component, hydrophilicity can be imparted to the surface of the flow channel 12. Thereby, the fluid (for example, aqueous solution) can be easily flowed in the flow channel 12. Such a function of imparting hydrophilicity can be realized by, for example, a substance having a hydroxyl group, an ionic group, or a group (group having a biased charge) that is largely polarized in the molecule.

  Contrary to the above, hydrophobicity can be imparted to the surface of the flow channel 12 by including a substance having a hydrophobic group as a functional component. Thereby, it is possible to make it difficult for a fluid (for example, an aqueous solution) to flow in the flow channel 12. Therefore, for example, when there is a reaction field of the sample in the flow channel 12, the sample can stay in the reaction field for a long time, and the reaction rate can be increased. Such a function of imparting hydrophobicity can be realized, for example, by a substance having a long-chain hydrocarbon group, a cyclic olefin group, or a phenyl group.

  In addition, by including both a substance having a hydrophilic group and a substance having a hydrophobic group as the functional component, the flow of fluid can be easily controlled according to the position in the flow channel 12. . In this case, a substance having a hydrophilic group and a substance having a hydrophobic group are preferably patterned on the functional component-containing layer 21 in accordance with the flow of fluid.

  By including an antistatic agent as a functional component, charging on the surface of the channel groove 12 can be suppressed. Thereby, for example, when analysis by capillary electrophoresis is performed using the microchannel chip 1, the influence on the capillary electrophoresis can be reduced. Such an antistatic function can be realized by, for example, a conductive polymer or metal powder.

  By including a cationic polymer, an anionic polymer, or a zwitterionic polymer as a functional component, a charge can be imparted to the surface of the flow channel 12. Thereby, for example, when a charged substance is present in the fluid, the charged substance can be trapped and separated from other components in the fluid.

  By including a protein low-adsorbing substance as a functional component, it is possible to suppress nonspecific adsorption of proteins to the surface of the flow channel 12. Therefore, the analysis accuracy can be increased. Such a low protein adsorption function can be realized by, for example, AWP (ammonium tungstate) or MPC polymer (poly (2-methacryloyloxyethyl phosphorylcholine)).

  By including one component involved in a specific reaction or specific binding as a functional component, a specific reaction can be caused in the flow channel 12 or a specific component can be extracted or removed. As the specific reaction, for example, an enzyme reaction can be exemplified. In this case, an enzyme or a substrate corresponding thereto can be included in the functional component-containing layer 21 as a functional component. As specific binding, for example, an antigen-antibody reaction can be exemplified. In this case, an antigen or an antibody corresponding thereto can be included in the functional component-containing layer 21 as a functional component.

  By including a primer in the polymerase chain reaction as a functional component, PCR (polymerase chain reaction) can be performed in the channel groove 12. Thereby, the DNA fragment of a specific sequence can be amplified.

  Such various functional components may be used singly or in any combination as required. When a plurality of types of functional components are used in combination, the existence region of each functional component in the functional component-containing layer 21 may be divided for each functional component.

  Although the thickness of the functional component content layer 21 is not specifically limited, For example, it is 1 nm or more and 10 micrometers or less.

  The resin substrate 10 and the resin film 20 are such that the first surface 10a of the resin substrate 10 on which the flow channel grooves 12 are formed and the first surface 20a of the resin film 20 on which the functional component-containing layer 21 is formed face each other. Are stacked. That is, the resin film 20 is joined to the resin substrate 10 so as to cover the flow channel 12, thereby forming a micro flow channel including the flow channel 12 between the resin substrate 10 and the resin film 20. The And the functional component content layer 21 of the resin film 20 is provided in the state exposed to the microchannel.

  As shown in FIG. 2, the manufacturing method of the microchannel chip 1 described above includes a resin film 20 and a peeling film 22 bonded to the resin film 20, and includes the resin film 20 and the peeling film 22. A preparation step for preparing the laminated film 2 having the functional component-containing layer 21 provided so as to be peelable from the peeling film 22 between, a peeling step for peeling the peeling film 22 from the laminated film 2, and a step after the peeling step It includes a bonding step of bonding the resin film 20 from the exposed surface side to the surface of the resin substrate 10 where the flow channel grooves 12 are formed.

  In the preparation step, a functional component or a pressure-sensitive adhesive containing the functional component is applied to the entire first surface 22a, which is one surface of the peeling film 22, or to the entire first surface 20a of the resin film 20. The functional component-containing layer 21 may be formed, and the functional component-containing layer 21 may be formed on the first surface 22a of the peeling film 22 or the first surface 20a of the resin film 20 by a known microcontact printing method. It can also be patterned. The applicable peeling film 22 is not particularly limited as long as it can be peeled from the functional component-containing layer 21. The laminated film 2 can be cut into a desired size, for example, from what is stored in a roll state, and can be used in a subsequent process.

  In the peeling step, the functional film-containing layer 21 is exposed by peeling off the peeling film 22 of the laminated film 2.

  In the bonding step, the resin film 20 is bonded to the resin substrate 10 so as to cover the flow channel 12. In that case, a resin film is joined so that the functional component content layer 21 in the resin film 20 after a peeling process may be arrange | positioned in the flow-path groove | channel 12 in the resin substrate 10. FIG. As a result, a micro flow path including the flow path groove 12 is formed between the resin substrate 10 and the resin film 20. Since it is not necessary to go through a washing process after peeling off the peeling film 22 in the peeling process, contamination of the flow path can be prevented while simplifying the manufacturing process. In this joining step, a method of joining the resin substrate 10 and the resin film 20 by thermocompression bonding of the laminate of the resin substrate 10 and the resin film 20 with a known hot press machine is desirable.

  In the manufacturing method described above, when a microchannel chip having a plurality of types of functions is manufactured, for example, a plurality of laminated films 2 having functional component-containing layers 21 having different functions are formed on the first surface of the resin substrate 10. It can be produced by using the laminated film 2 having the functional component-containing layer 21 having a plurality of different functions. In addition, about the laminated | multilayer film 2 which has the functional component containing layer 21 with a several different function, the 1st surface 22a of the film 22 for peeling or the 1st surface of the resin film 20 is known by the well-known microcontact printing method, for example. The functional component-containing layer 21 can be formed by patterning a plurality of types of functional components in 20a.

[Other Embodiments]
In the above-described embodiment, a form using a resin substrate that has no particular function is illustrated, but the present invention is not limited to this configuration, and a resin substrate having some function is used as necessary. Also good. For example, when the functional component-containing layer is a layer containing a hydrophilic group, the resin substrate may be made of a hydrophilic resin material. As described above, when the function of the functional component-containing layer and the function of the resin substrate are made the same, a microchannel chip having higher chemical reactivity and separation / analysis performance can be obtained. it can.

  The embodiments of the microchannel chip and the manufacturing method thereof have been described in detail with specific examples. However, the scope of the present invention is not limited to the specific embodiments described above. The embodiments disclosed in this specification are exemplifications in all respects, and can be appropriately modified without departing from the gist of the present invention.

DESCRIPTION OF SYMBOLS 1 Microchannel chip 2 Laminated | multilayer film 10 Resin board | substrate 10a 1st surface (one surface)
10b Second surface 12 Channel groove 14 Port 20 Resin film 21 Functional component containing layer 22 Peeling film

Claims (17)

A method of manufacturing a microchannel chip, comprising: a resin substrate having a channel groove on one surface; and a resin film bonded to the resin substrate so as to cover the channel groove,
While having the said resin film and the film for peeling bonded together to the said resin film, it has a functional component content layer provided so that peeling was possible from the said film for peeling between the said resin film and the said film for peeling. A preparation step of preparing a laminated film;
A peeling step of peeling the peeling film from the laminated film;
A bonding step of bonding the resin film after the peeling step from an exposed surface side to a surface of the resin substrate on which the flow channel groove is formed;
The manufacturing method of the microchannel chip containing this.   The method for producing a microchannel chip according to claim 1, wherein the functional component-containing layer is a layer containing at least one of a hydrophilic group and a hydrophobic group.   The functional component-containing layer is a layer containing both a hydrophilic group and a hydrophobic group, and the functional component contains the hydrophilic component and the hydrophobic group according to the flow of fluid in the flow channel. The method for manufacturing a microchannel chip according to claim 2, wherein the microchannel chip is patterned on the containing layer.   The method for producing a microchannel chip according to claim 1, wherein the functional component-containing layer is a layer containing an antistatic agent.   The method for producing a microchannel chip according to claim 1, wherein the functional component-containing layer is a layer containing any one of a cationic polymer, an anionic polymer, and a zwitterionic polymer.   The method for producing a microchannel chip according to claim 1, wherein the functional component-containing layer is a layer containing a low protein-adsorbing substance.   The method for producing a microchannel chip according to claim 1, wherein the functional component-containing layer is a layer containing one component involved in specific reaction or specific binding.   The method for producing a microchannel chip according to claim 1, wherein the functional component-containing layer is a layer containing a primer in a polymerase chain reaction.   The method for manufacturing a microchannel chip according to claim 1, wherein in the preparation step, the functional component-containing layer is patterned by a microcontact printing method. A resin substrate having a channel groove on one surface;
A resin film bonded to the resin substrate,
The microchannel chip which has a functional ingredient content layer in the portion which covers the channel groove among the resin films.   The microchannel chip according to claim 10, wherein the functional component-containing layer is a layer containing at least one of a hydrophilic group and a hydrophobic group.   The functional component-containing layer is a layer containing both a hydrophilic group and a hydrophobic group, and the functional component contains the hydrophilic component and the hydrophobic group according to the flow of fluid in the flow channel. The microchannel chip according to claim 11, wherein the microchannel chip is patterned on the containing layer.   The microchannel chip according to claim 10, wherein the functional component-containing layer is a layer containing an antistatic agent.   The microchannel chip according to claim 10, wherein the functional component-containing layer is a layer containing a cationic polymer, an anionic polymer, or a zwitterionic polymer.   The microchannel chip according to claim 10, wherein the functional component-containing layer is a layer containing a low protein-adsorbing substance.   The microchannel chip according to claim 10, wherein the functional component-containing layer is a layer containing one component involved in a specific reaction or specific binding. The microchannel chip according to claim 10, wherein the functional component-containing layer is a layer containing a primer in a polymerase chain reaction.

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