Biosensor
One object of the present invention is to provide a biosensor and a production method therefor, by which hydrogel that enables immobilization of a physiologically active substance can be conveniently produced using safe raw materials. The present invention provides a biosensor which comprises a substrate having a metal layer on its surface, wherein a hydrophilic polymer having a reactive functional group capable of reacting with a hydroxyl group or an amino group of a physiologically active substance is bound to the metal layer directly or indirectly via an intermediate layer.
1 . A biosensor which comprises a substrate having a metal layer on its surface, wherein a hydrophilic polymer having a reactive functional group capable of reacting with a hydroxyl group or an amino group of a physiologically active substance is bound to the metal layer directly or indirectly via an intermediate layer.
2 . The biosensor according to claim 1 , wherein the reactive functional group of the hydrophilic polymer is a vinylsulfone group or a precursor thereof.
3 . The biosensor according to claim 1 , wherein the reactive functional group of the hydrophilic polymer is a dichlorotriazine group.
4 . The biosensor according to claim 1 , which is obtained by forming a dense layer on the metal surface using an alkanethiol having a reactive group at its terminus or a disulfide that is an oxidized product of the alkanethiol, and then allowing the reactive group at the terminus of the alkanethiol to react with a hydrophilic polymer having a reactive functional group capable of reacting with a hydroxyl group or an amino group of a physiologically active substance.
5 . The biosensor according to claim 1 , wherein a carboxylic acid is introduced by allowing the reactive functional groups of the hydrophilic polymer to react with an amino acid.
6 . The biosensor according to claim 1 , which is used in surface plasmon resonance analysis.
7 . A method for producing the biosensor according to claim 1 , which comprises a step of chemically binding a hydrophilic polymer having a reactive functional group capable of reacting with a hydroxyl group or an amino group of a physiologically active substance to the surface of a substrate having a metal layer on its surface directly or indirectly via an intermediate layer.
8 . A method for detecting or measuring a substance interacting with a physiologically active substance, which comprises a step of allowing a test substance to come into contact with the biosensor of claim 1 to the surface of which the physiologically active substance binds via a covalent bond.
9 . A biosensor which comprises a surface having a reactive group capable of chemically immobilizing a physiologically active substance and a cationic group.
10 . The biosensor according to claim 9 , wherein the surface comprising a reactive group capable of chemically immobilizing a physiologically active substance and a cationic group is a surface having a water-soluble polymer bound thereto, a surface having a hydrophobic polymer bound thereto, or a surface having a self-assembling monolayer film formed thereon.
11 . The biosensor according to claim 9 , wherein the reactive group capable of chemically immobilizing a physiologically active substance is a vinylsulfone group or a precursor thereof, a halotriazine group, an epoxy group, a carboxylic active ester group, an aldehyde group, an isocyanate group, or an acetoacetyl group.
12 . The biosensor according to claim 9 , wherein the cationic group is an onium or a precursor thereof.
13 . The biosensor according to claim 9 , which is used in surface plasmon resonance analysis.
14 . A method for immobilizing a physiologically active substance, which comprises allowing a solution containing a physiologically active substance and having a pH that is the isoelectric point or higher to come into contact with a surface having a reactive group capable of chemically immobilizing a physiologically active substance and a cationic group.
15 . A method for detecting or measuring a substance interacting with a physiologically active substance, which comprises a step of allowing a test substance to come into contact with the biosensor of claim 9 to the surface of which the physiologically active substance binds via a covalent bond.
16 . A biosensor which comprises a surface having a reactive group capable of chemically immobilizing a physiologically active substance and an anionic group having an acid dissociation constant that is lower than that of a carboxyl group.
17 . The biosensor according to claim 16 , wherein the surface having a reactive group capable of chemically immobilizing a physiologically active substance and an anionic groups having an acid dissociation constant that is lower than that of a carboxyl group is a surface having a water-soluble polymer bound thereto, a surface having a hydrophobic polymer bound thereto, or a surface having a self-assembling monolayer film formed thereon.
18 . The biosensor according to claim 16 , which is obtained by coating a substrate with a polymer having a reactive group capable of chemically immobilizing a physiologically active substance and an anionic group having an acid dissociation constant that is lower than that of a carboxyl group.
19 . The biosensor according to claim 16 , wherein the reactive group capable of chemically immobilizing a physiologically active substance is a vinylsulfone group or a precursor thereof, a halotriazine group, an epoxy group, a carboxylic active ester group, an aldehyde group, an isocyanate group, or an acetoacetyl group.
20 . The biosensor according to claim 16 , wherein the anionic group having an acid dissociation constant that is lower than that of a carboxyl group is a sulfuric ester group, a phosphoric ester group, or a sulfonic acid group.
21 . The biosensor according to claim 16 , which is used in surface plasmon resonance analysis.
22 . A method for immobilizing a physiologically active substance, which comprises allowing a solution containing a physiologically active substance to come into contact with a surface having a reactive group capable of chemically immobilizing a physiologically active substance and an anionic group having an acid dissociation constant that is lower than that of a carboxyl group.
23 . A method for detecting or measuring a substance interacting with a physiologically active substance, which comprises a step of allowing a test substance to come into contact with the biosensor of claim 16 to the surface of which the physiologically active substance binds via a covalent bond.
24 . An agent for immobilizing a physiologically active substance, which comprises a polymer having, within a molecule, a reactive group capable of chemically immobilizing a physiologically active substance and an cationic group.
25 . The agent for immobilizing a physiologically active substance according to claim 24 , wherein the reactive group capable of chemically immobilizing a physiologically active substance is a vinylsulfone group or a dichlorotriazine group.
26 . The agent for immobilizing a physiologically active substance according to claim 24 , wherein the cationic group is a primary amine salt, a secondary amine salt, a tertiary amine salt, or a quaternary ammonium compound.
27 . The agent for immobilizing a physiologically active substance according to claim 24 , wherein the polymer is a vinyl polymer, a polymer obtained by copolymerization of acrylamide monomer or (meth)acrylamide monomer, or a polysaccharide or a derivative thereof.
28 . A method for immobilizing a physiologically active substance, which comprises allowing a physiologically active substance to come into contact with a substrate having the agent for immobilizing a physiologically active substance according to claim 24 on its surface so as to chemically bind the physiologically active substance to the agent for immobilizing a physiologically active substance.