Biochip and method for manufacturing biochip

Abstract

Disclosed are a biochip capable of detecting and analyzing multivalent bindings between target protein and binding mediator from monovalent bindings and a method for manufacturing the same. A biochip according to an embodiment comprises: a hydrogel functional layer on which a binding mediator is formed and of which physical properties are changed by a reaction between target protein to be introduced and the binding mediator; and a transducer configured to deliver a displacement signal corresponding to a change in the physical properties of the hydrogel functional layer to an analysis instrument, wherein the reaction is multivalent bindings between the target protein and the binding mediator, and de-swelling occurs in at least a portion of the hydrogel functional layer by the multivalent bindings.

1 . A method of manufacturing a hydrogel functional layer disposed on a substrate of a biochip, the method comprising:
 mixing 55 to 98% of a main monomer, 2 to 40% of comonomers and 0.1 to 5% of a crosslinking agent so that a sum of the main monomer, the comonomers, and the crosslinking agent is 100%;   heating an aqueous solution containing the main monomer and the comonomers;   initiating a reaction by adding an initiator; and   acquiring an aqueous hydrogel solution generated by the reaction.   
     
     
         2 . The method of  claim 1 , wherein the acquiring of the aqueous hydrogel solution comprises maintaining an oxygen-free environment while heating the aqueous solution. 
     
     
         3 . The method of  claim 1 , wherein a hydrogel of the hydrogel functional layer is in a form of nanoparticles. 
     
     
         4 . The method of  claim 1 , wherein the hydrogel functional layer comprises at least one selected from the group consisting of poly(N-isopropylacrylamide-co-allylamine) (poly(NIPAM-co-AA)), poly(N-isopropylacrylamide-co-2-(dimethylamino)ethyl methacrylate) (poly(NIPAM-co-DMAEMA)), poly(N-isopropylacrylamide-co-2-(dimethylamino)ethyl acrylate) (poly(NIPAM-co-DMAEA)), poly(N-isopropylacrylamide-co-acrylic acid) (poly(NIPAM-co-AAc)), poly(N-isopropylacrylamide-co-polyethylene glycol-acrylic acid) (poly(NIPAM-co-PEG-AAc)), [poly(N-isopropylacrylamide-co-methacrylic acid) (poly(NIPAM-co-MAAc)), N-isopropylacrylamide, poly(N-acryloylglycinamide), hydroxypropylcellulose, poly(vinylcaprolactame) and polyvinyl methyl ether. 
     
     
         5 . The method of  claim 1 , wherein the substrate is activated with at least one of positive charge, negative charge, epoxy and mercapto. 
     
     
         6 . The method of  claim 5 , wherein the at least one of positive charge, negative charge, epoxy and mercapto comprises at least one of aminosilane, carboxylsilane, epoxysilane and mercaptosilane. 
     
     
         7 . The method of  claim 1 , further comprising:
 modifying a surface of the hydrogel functional layer by forming at least one of a ligand, a receptor, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) on the surface of the hydrogel functional layer.   
     
     
         8 . The method of  claim 1 , further comprising:
 modifying a surface of the hydrogel functional layer using at least one of nanoparticles and protein as a coupling moiety to form at least one of a ligand, a receptor, DNA and RNA on the surface of the hydrogel functional layer.   
     
     
         9 . A hydrogel functional layer disposed on a substrate of a biochip manufactured by the method of  claim 1 . 
     
     
         10 . The hydrogel functional layer of  claim 9 , wherein a hydrogel of the hydrogel functional layer is in a form of nanoparticles. 
     
     
         11 . The hydrogel functional layer of  claim 9 , wherein the substrate is activated with at least one of positive charge, negative charge, epoxy and mercapto. 
     
     
         12 . The hydrogel functional layer of  claim 9 , wherein the method further comprises:
 modifying a surface of the hydrogel functional layer by forming at least one of a ligand, a receptor, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) on the surface of the hydrogel functional layer.   
     
     
         13 . The hydrogel functional layer of  claim 9 , wherein the method further comprises:
 modifying a surface of the hydrogel functional layer using at least one of nanoparticles and protein as a coupling moiety to form at least one of a ligand, a receptor, DNA and RNA on the surface of the hydrogel functional layer.