Gene detection field-effect device and method of analyzing gene polymorphism therewith

Abstract

A gene detection field-effect device provided with an insulation film ( 2 ), a semiconductor substrate ( 3 ), and a reference electrode ( 4 ), includes: (a) the insulation film ( 2 ) including a nucleic acid probe ( 5 ) immobilized on one of the surfaces thereof and is in contact with a sample solution ( 6 ) containing at least one type of a target gene ( 601 ) for detection and analysis; (b) the semiconductor substrate ( 3 ) being installed so as to abut against the other surface of the insulation film ( 2 ); and (c) the reference electrode ( 4 ) being provided in the sample solution ( 6 ).

1 - 9 . (canceled) 
     
     
         10 . A gene polymorphism measuring system having at least a flow cell, a flow channel and a signal processing circuit, comprising:
 (a) the flow cell including therein a gene detection field-effect device provided with an insulation film including a nucleic acid probe immobilized on one of the surfaces thereof, a semiconductor substrate being installed so as to abut against the other surface of the insulation film, and a reference electrode;   (b) the flow channel for introducing a sample solution to the gene detection field-effect device being connected to the flow cell; and   (c) the flow cell being connected to the signal processing circuit for processing a signal detected by the gene detection field-effect device.   
     
     
         11 . The gene polymorphism measuring system according to  claim 10 , wherein at least two of the gene detection field-effect devices are provided and at least two types of nucleic acid probes including a wild-type (normal-type) nucleic acid probe having a base sequence which is complementary with a base sequence of a target gene and a mutant-type nucleic acid probe having a base sequence which is complementary with the mutant-type base sequence of the target gene are immobilized to the respective insulation films of the gene detection field-effect devices. 
     
     
         12 . The gene polymorphism measuring system according to  claim 11 , wherein a base at a non-immobilized end, which is an end of the nucleic acid probe not immobilized to the insulation film of the mutant-type nucleic acid probe is different from a base at a non-immobilized end of a wild-type nucleic acid probe. 
     
     
         13 . The gene polymorphism measuring system according to  claim 10 , wherein at least one type of the nucleic acid probe is selected from the group consisting of oligonucleotide, a complementary DNA (cDNA) and peptide nucleic acid (PNA). 
     
     
         14 . The gene polymorphism measuring system according to  claim 10 , wherein the nucleic acid probe is immobilized via a metal electrode. 
     
     
         15 . The gene polymorphism measuring system according to  claim 14 , wherein at least one type of the metal electrode is selected from the group consisting of white gold, gold, silver, palladium, titan, and chrome. 
     
     
         16 . The gene polymorphism measuring system according to  claim 10 , wherein a heater and a temperature sensor are further integrated. 
     
     
         17 . The gene polymorphism measuring system according to  claim 10 , wherein the insulation film is formed of silicon nitride. 
     
     
         18 . The gene polymorphism measuring system according to  claim 10 , wherein Taq DNA polymerase as an enzyme for elongation and deoxyadenosine triphosphoric acid (dATP), deoxyguanosine triphosphate (dGTP), deoxycytidine triphosphate (dCTP), and deoxythymidine triphosphate (dTTP) as ground substances are introduced on the insulation film for effecting elongation. 
     
     
         19 . The gene polymorphism measuring system according to  claim 10 , wherein a differential output value V1 between a first gene detection field-effect device in which a wild-type nucleic acid probe is immobilized and a third gene detection field-effect device in which a nucleic acid probe is not immobilized on the insulation film is measured; a differential output value V2 between a second gene detection field-effect device in which a mutant-type nucleic acid probe is immobilized and a third gene detection field-effect device is measured, and classification into three patterns; a pattern in which V1 is larger than V2 (V1>V2), a pattern in which V1 and V2 is almost the same (V1≈V2), and a pattern in which V1 is smaller than V2 (V1<V2) is performed and displayed; and an output value of the gene detection field-effect device is measured.