Chip Provided with film Having Hole Pattern with the Use of Thermoresponsive Polymer and Method of Producing the Same

Abstract

[Problems] To provide a novel chip useful for treating cells and the like which has a mechanism and a structure wherein the size of a hole pattern is arbitrarily changed so that cells can easily move in and get out from the hole in scattering or collecting cells but can hardly get out from the hole during washing or antigen-stimulation. [Means for Solving Problems] A chip comprising a crosslinked product of a temperature-responsive polymer as a constituting member and being provided with a film having a hole pattern on the surface of a baseboard. A method of producing a chip which comprises a crosslinked product of a temperature-responsive polymer as a constituting member and is provided with a film having a hole pattern on the surface of the baseboard. This method comprises applying a composition containing a crosslinkable temperature-responsive polymer, a composition containing a crosslinkable temperature-responsive polymer and a crosslinking agent or a composition containing a temperature-responsive polymer and a crosslinking agent on the surface of a baseboard to thereby form a coating film, crosslinking the coating film to thereby form the crosslinked product as described above and then forming a hole pattern on the coating film of the crosslinked product.

1 . A chip comprising:
 a crosslinked product of a temperature-responsive polymer as a constituting member and being provided with a film having a hole pattern on the surface of a substrate.   
   
   
       2 . The chip according to  claim 1 , wherein the crosslinked product of the temperature-responsive polymer is either a crosslinked product between the temperature-responsive polymers or a crosslinked product through a crosslinker. 
   
   
       3 . The chip according to  claim 1 , wherein the crosslinked product of the temperature-responsive polymer is a crosslinked product of an N-alkyl (meth)acrylamide copolymer having a recurring unit represented by general formula (1): 
     
       
         
         
             
             
         
       
       wherein R 1  and R 2  may be the same as or different from each other and represent a hydrogen atom or an (1-4C) alkyl group; R 3  represents a hydrogen atom or a methyl group; R 4  represents a hydrocarbon structure having a functional group crosslinkable with the above crosslinker; x and y are any numbers satisfying numerical formulae: x+y=1, 0<x<1, and 0<y<1, and having a weight average molecular weight of 500 to 5,000,000, with a crosslinker. 
     
   
   
       4 . The chip according to  claim 1 , wherein the film having a hole pattern has a thickness ranging from 10 nm to 100 μm. 
   
   
       5 . The chip according to  claim 1 , wherein the hole of the hole pattern has such a size that an inscribed circle thereof has a diameter ranging from 10 nm to 1000 μm. 
   
   
       6 . The chip according to  claim 1 , wherein the hole of the hole pattern has a depth ranging from 10 nm to 100 μm. 
   
   
       7 . The chip according to  claim 1 , wherein the hole of the hole pattern is provided in a density of 1 to 1,000,000,000 pieces/cm 2 . 
   
   
       8 . The chip according to  claim 1 , wherein the substrate has concave portions below at least a part of the holes which the film has on the surface of the substrate on which the film is provided. 
   
   
       9 . The chip according to  claim 1 , wherein the hole of the hole pattern has on the surface of the substrate therein, a dot formed with the crosslinked product of the temperature-responsive polymer which is independent from the film. 
   
   
       10 . The chip according to  claim 1 , wherein the size of the hole of the hole pattern is changed arbitrarily by changing a part of or the whole of the film temperature to swell or contract a part of or the whole of the film. 
   
   
       11 . The chip according to  claim 10 , wherein a biological material housed in the hole of the hole pattern is caused to be either in a clathrated state or in a liberated state depending on the change in the film temperature. 
   
   
       12 . A method for clathrating a biological material in the hole pattern of the chip, the method comprising:
 controlling the film temperature of the chip according to  claim 1  to a temperature at which the diameter of the hole of the hole pattern which the chip has become a size capable of housing the biological material;   housing the biological material in the hole of the hole pattern; and   controlling the film temperature of the chip to a temperature at which the diameter of the hole having housed the biological material becomes a size capable of clathrating the biological material.   
   
   
       13 . A method for liberating the biological material clathrated in the chip, the method comprising:
 controlling the film temperature of the chip having clathrated the biological material by the method according to  claim 12  to a temperature at which the diameter of the hole of the hole pattern of the chip becomes a size capable of liberating the biological material.   
   
   
       14 . A production method of a chip that includes a crosslinked product of a temperature-responsive polymer as a constituting member and is provided with a film having a hole pattern on the surface of the substrate, the method comprising:
 forming a coated film by applying to the surface of the substrate, a composition containing a crosslinkable temperature-responsive polymer, a composition containing a crosslinkable temperature-responsive polymer and a crosslinker, or a composition containing a temperature-responsive polymer and a crosslinker;   crosslinking the coated film to form the crosslinked product; and   forming the hole pattern on the coated film of the crosslinked product.   
   
   
       15 . The production method according to  claim 14 , wherein the composition containing the crosslinkable temperature-responsive polymer and a crosslinker or the composition containing a temperature-responsive polymer and a crosslinker is a composition containing an N-alkyl (meth)acrylamide copolymer having a recurring unit represented by general formula (1): 
     
       
         
         
             
             
         
       
       wherein R 1  and R 2  may be the same as or different from each other and represent a hydrogen atom or an (1-4C) alkyl group; R 3  represents a hydrogen atom or a methyl group; R 4  represents a hydrocarbon structure having a functional group crosslinkable with the above crosslinker; x and y are any numbers satisfying numerical formulae: x+y=1, 0<x<1, and 0<y<1; and here, (meth)acrylamide represents both methacrylamide and acrylamide, and having a weight average molecular weight of 500 to 5,000,000, and a crosslinker. 
     
   
   
       16 . A production method of a chip that includes a crosslinked product of a temperature-responsive polymer as a constituting member and is provided with a film having a hole pattern on the surface of a substrate, the method comprising:
 forming a coated film by applying to the surface of the substrate, a composition containing a monomer for forming a crosslinkable temperature-responsive polymer, a composition containing a monomer for forming a crosslinkable temperature-responsive polymer and a crosslinker, or a composition containing a monomer for forming a temperature-responsive polymer and a crosslinker;   polymerizing and crosslinking the coated film to form the crosslinked product; and   forming the hole pattern on the coated film of the crosslinked product.   
   
   
       17 . The production method according to  claim 14 , wherein the substrate to which the composition is applied is a silicon substrate, a glass substrate, a plastic substrate, a mica substrate, a ceramic substrate or a metal substrate. 
   
   
       18 . The production method according to  claim 14 , wherein the application of the composition to the substrate comprises:
 dissolving the composition in a solvent;   dropping the resultant solution onto the substrate; and   evaporating the solvent to obtain a coated film.   
   
   
       19 . The production method according to  claim 14 , wherein the formation of the hole pattern on the coated film is performed by a photolithography method. 
   
   
       20 . The production method according to  claim 19 , wherein
 the formation of the hole pattern on the coated film by a photolithography method includes:   incorporating further an acid generator in the composition for forming the coated film;   irradiating, after forming the coated film, a radiation for activating the acid generator through a mask for forming the hole pattern to the coated film;   crosslinking a part of the coated film to which a radiation has been irradiated; and   removing, after removing the mask, a part of the coated film which has not been crosslinked.   
   
   
       21 . The production method according to  claim 20 , wherein the acid generator is at least one selected from the group consisting of an onium salt, sulfonyloxyimide, triazine, and a sulfonate ester. 
   
   
       22 . The production method according to  claim 20 , wherein the radiation is a mercury lamp light, an electron beam, an excimer laser, an X ray or a xenon lamp. 
   
   
       23 . The production method according to  claim 14 , wherein the forming of the hole pattern on the coated film is performed by a screen printing method, an inkjet method, a contact printing method or an emboss processing method. 
   
   
       24 . The production method according to  claim 23 , wherein the forming of the hole pattern on the coated film by a screen printing method, an inkjet method, a contact printing method or an emboss processing method is performed by forming the hole pattern on the coated film before the crosslinking and then by crosslinking the coated film on which the hole pattern has been formed. 
   
   
       25 . The production method according to  claim 15 , wherein the hydrocarbon structure having a functional group crosslinkable with the crosslinker is a (meth)acrylate structure or a (meth)acrylamide structure (here, the (meth)acrylate represents both methacrylate and acrylate) having in a side chain thereof, a functional group crosslinkable with the crosslinker. 
   
   
       26 . The production method according to  claim 15 , wherein the functional group crosslinkable with the crosslinker is a hydroxyl group, a carboxyl group, an epoxy group, an amino group or a succinimide group. 
   
   
       27 . The production method according to  claim 15 , wherein the crosslinker is an epoxy-based crosslinker, a melamine-based crosslinker, a glycouril-based crosslinker, or a compound having two or more of hydroxyl groups, carboxyl groups, azide groups, or vinylether groups. 
   
   
       28 . The production method according to  claim 26 , wherein the compound having two or more of hydroxyl groups, carboxyl groups, azide groups, or vinylether groups is 1,2-dihydroxynaphthalene, 1,3-dihydroxynaphthalene, 1,4-dihydroxynaphthalene, 1,5-dihydroxynaphthalene, 1,6-dihydroxynaphthalene, 1,7-dihydroxynaphthalene, 1,8-dihydroxynaphthalene, 2,3-dihydroxynaphthalene, 2,6-dihydroxynaphthalene, 2,7-dihydroxynaphthalene, 1,3-cyclopentanediol, 2,6-quinolinediol, 2,3-dihydroxyquinoxaline, 1,4-dioxanediol, 1,4-cyclohexanedimethanol, polyvinyl alcohol, 1,2-naphthalene dicarboxylic acid, 1,3-naphthalene dicarboxylic acid, 1,4-naphthalene dicarboxylic acid, 1,5-naphthalene dicarboxylic acid, 1,6-naphthalene dicarboxylic acid, 1,7-naphthalene dicarboxylic acid, 1,8-naphthalene dicarboxylic acid, 2,3-naphthalene dicarboxylic acid, 2,6-naphthalene dicarboxylic acid, cyclohexane dicarboxylic acid, terephthalic acid, 1,2-cyclopentane dicarboxylic acid, 2,5-thiophene dicarboxylic acid, 2-methyl-3,4-quinoline dicarboxylic acid, 9,10-anthracene dicarboxylic acid, dihydroanthracene-9,10-dicarboxylic acid, citric acid, succinic acid, polyacrylic acid, polymethacrylic acid, 2,6-bis(4-azidebenzilidene)cyclohexanone, bis(4-vinyloxybutyl) terephthalate or bis(4-vinyloxybutyl)adipate.