Ion sensitive field effect transistors

Abstract

According to a first aspect of the present invention there is provided a digital signal processing circuit, one or more switches of the circuit being provided by an ion sensitive field effect transistor.

1 . A digital signal processing circuit, one or more switches of the circuit being provided by an ion sensitive field effect transistor. 
   
   
       2 . A circuit according to  claim 1 , wherein the or each ion sensitive field effect transistor comprises an analyte sensitive membrane which is exposed in use to a medium to be monitored. 
   
   
       3 . A circuit according to  claim 1 , wherein the circuit is configured to operate as a comparator for comparing a value of a parameter measured by the ion sensitive field effect transistor with a threshold value, the circuit comprising an ion sensitive field effect transistor and a metal oxide semiconductor transistor arranged in an inverter configuration. 
   
   
       4 . A circuit according to  claim 3 , wherein one of the ion sensitive field effect transistor and the metal oxide semiconductor transistor is an n-channel device and the other is a p-channel device. 
   
   
       5 . A circuit according to  claim 1 , wherein the digital signal processing circuit is arranged to implement one or more of the following functions: AND, NAND, OR, XOR, NOR. 
   
   
       6 . A circuit according to  claim 1 , wherein the digital signal processing circuit uses CMOS logic. 
   
   
       7 . A circuit according to  claim 1 , wherein the digital signal processing circuit comprises biasing means for biasing the or each ion sensitive field effect transistor in the weak inversion region. 
   
   
       8 . A device for detecting a plurality of chemical reactions and evaluating a logical function having the result of each of the plurality of chemical reactions as its inputs, the device comprising:
 at least one reaction chamber for each of the plurality of chemical reactions; and   each reaction chamber being provided with an ion sensitive field effect transistor configured to operate as a switch for detecting one of the plurality of chemical reactions, the ion sensitive field effect transistors being coupled together to form a digital signal processing circuit for evaluating the logical function.   
   
   
       9 . A device according to  claim 8 , wherein one or more of the ion sensitive field effect transistors comprise an analyte sensitive membrane that is exposed within the reaction chamber. 
   
   
       10 . A device according to  claim 8 , wherein the digital signal processing circuit is arranged to implement one or more or a combination of the following functions: AND, NAND, OR, XOR, NOR. 
   
   
       11 . A device according to  claim 8 , wherein the digital signal processing circuit uses CMOS logic. 
   
   
       12 . A device according to  claim 8 , wherein the digital signal processing circuit comprises biasing means for biasing one or more of the ion sensitive field effect transistors in the weak inversion region. 
   
   
       13 . A method of evaluating a logical function having as one of its inputs the value of a parameter of a medium, the method comprising:
 configuring an ion sensitive field effect transistor to operate as a switch of a logic circuit; and   exposing the ion sensitive field effect transistor to said medium.   
   
   
       14 . A method according to  claim 13 , the method further comprising configuring the ion sensitive field effect transistor to switch when a change in the concentration of hydrogen ions in the medium indicates incorporation of a nucleotide into a sample of genetic material. 
   
   
       15 . A method of detecting a plurality of chemical reactions and evaluating a logical function having the result of each of the plurality of chemical reactions as its inputs, the method comprising:
 for each of the plurality of chemical reactions, configuring at least one ion sensitive field effect transistor to operate as a switch of a logic circuit, and exposing the ion sensitive field effect transistor to the chemical reaction.   
   
   
       16 . A method according to  claim 15 , the method further comprising configuring one or more of the ion sensitive field effect transistors to switch when a change in the concentration of hydrogen ions in the medium indicates incorporation of a nucleotide into a sample of genetic material. 
   
   
       17 . A method of detecting the presence of a unique genetic sequence in a target sample of single-stranded genetic material, the method comprising:
 performing a hybridisation reaction involving said target sample and a nucleotide probe, the nucleotide probe being configured to complement the unique genetic sequence;   configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of one or more nucleotides into genetic material;   exposing the ion sensitive field effect transistor to a solution comprising a product of the hybridisation reaction and an excess of all nucleotides; and   monitoring the output of the ion sensitive field effect transistor to determine whether it switches and to thereby determine whether the probe has hybridised with the target sample.   
   
   
       18 . A method of detecting the presence of a plurality of unique genetic sequences in a target sample of single-stranded genetic material, the method comprising:
 for each of the plurality of unique genetic sequences:
 performing a hybridisation reaction involving said target sample and a nucleotide probe, the nucleotide probe being configured to complement the unique genetic sequence; 
 configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of one or more nucleotides into genetic material; 
 exposing the ion sensitive field effect transistor to a solution comprising a product of the hybridisation reaction and an excess of all nucleotides; and 
   configuring the ion sensitive field effect transistors into a digital processing circuit to provide an output of a logical function as an indication of the presence or absence of each of the plurality of unique genetic sequences.   
   
   
       19 . A method of identifying a nucleotide present at a specific location in a target sample of single-stranded genetic material, the method comprising:
 performing a hybridisation reaction involving said target sample and a nucleotide probe in order to form a probe-target hybrid, the nucleotide probe being configured to uniquely identify the specific location;   for each candidate nucleotide that may be present at the specific location:
 configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of a nucleotide into genetic material; 
 exposing the ion sensitive field effect transistor to a solution comprising the probe-target hybrid and a nucleotide complementary to said candidate nucleotide; and 
   monitoring the output of the ion sensitive field effect transistors to determine which switches and to thereby determine which of said complementary nucleotides has been incorporated at the specific location.   
   
   
       20 . A method of identifying a nucleotide present at a specific location in a target sample of single-stranded genetic material, the method comprising:
 for each candidate nucleotide that may be present at the specific location:
 performing a hybridisation reaction involving said target sample and a nucleotide probe, the nucleotide probe being configured to uniquely locate a nucleotide complementary to the candidate nucleotide at the specific location; 
 configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of a plurality of nucleotides into genetic material; 
 exposing the ion sensitive field effect transistor to a solution comprising a product of the hybridisation reaction and an excess of all nucleotides; and 
   monitoring the outputs of the ion sensitive field effect transistors to determine which switches and to thereby determine which of the probes has hybridised with the target sample.   
   
   
       21 . A method of detecting the presence of a single nucleotide polymorphism in a target sample of single-stranded genetic material, the method comprising:
 performing a hybridisation reaction involving said target sample and a nucleotide probe in order to form a probe-target hybrid, the nucleotide probe being configured to uniquely identify the expected location of the single nucleotide polymorphism;   configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of a nucleotide into genetic material;   exposing the ion sensitive field effect transistor to a solution comprising the probe-target hybrid and a complementary nucleotide associated with the single nucleotide polymorphism; and   monitoring the output of the ion sensitive field effect transistor to determine whether it switches and to thereby determine whether the complementary nucleotide has been incorporated at the specific location.   
   
   
       22 . A method of detecting the presence of a single nucleotide polymorphism in a target sample of single-stranded genetic material, the method comprising:
 performing a hybridisation reaction involving said target sample and a nucleotide probe, the nucleotide probe being configured to uniquely locate a complementary nucleotide associated with the single nucleotide polymorphism at the expected location of the single nucleotide polymorphism;   configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of a plurality of nucleotides into genetic material;   exposing the ion sensitive field effect transistor to a solution comprising a product of the hybridisation reaction and an excess of all nucleotides; and   monitoring the outputs of the ion sensitive field effect transistor to determine whether it switches and to thereby determine whether the probe has hybridised with the target sample.   
   
   
       23 . A method of detecting the presence of a plurality of single nucleotide polymorphisms in a target sample of single-stranded genetic material, the method comprising:
 for each of the single nucleotide polymorphisms:
 performing a hybridisation reaction involving said target sample and a nucleotide probe in order to form a probe-target hybrid, the nucleotide probe being configured to uniquely identify the expected location of the single nucleotide polymorphism; 
 configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of a nucleotide into genetic material; 
 exposing the ion sensitive field effect transistor to a solution comprising the probe-target hybrid and a complementary nucleotide associated with the single nucleotide polymorphism; and 
   configuring the ion sensitive field effect transistors into a digital processing circuit to provide an output of a logical function as an indication of the presence or absence of each of the plurality of single nucleotide polymorphisms.   
   
   
       24 . A method of detecting the presence of a plurality of single nucleotide polymorphisms in a target sample of single-stranded genetic material, the method comprising:
 for each of the single nucleotide polymorphisms:
 performing a hybridisation reaction involving said target sample and a nucleotide probe, the nucleotide probe being configured to uniquely locate a complementary nucleotide associated with the single nucleotide polymorphism at the expected location of the single nucleotide polymorphism; 
 configuring an ion sensitive field effect transistor to operate as a switch, and to switch in the presence of the incorporation of a plurality of nucleotides into genetic material; 
 exposing the ion sensitive field effect transistor to a solution comprising a product of the hybridisation reaction and an excess of all nucleotides; and 
   configuring the ion sensitive field effect transistors into a digital processing circuit to provide an output of a logical function as an indication of the presence or absence of each of the plurality of single nucleotide polymorphisms.   
   
   
       25 . A method according to  claim 17  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle. 
   
   
       26 . A method according to  claim 18  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle. 
   
   
       27 . A method according to  claim 19  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle. 
   
   
       28 . A method according to  claim 20  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle. 
   
   
       29 . A method according to  claim 21  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle. 
   
   
       30 . A method according to  claim 22  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle. 
   
   
       31 . A method according to  claim 23  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle. 
   
   
       32 . A method according to  claim 24  wherein the hybridisation reaction occurs during a nucleic acid amplification cycle.