Methods for detecting a target molecule
First Claim
1. A method for detecting a target molecule, said method comprising:
- (a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium comprising a sample suspected of containing said target molecule, each of said electrodes comprising at least one target probe, (b) selectively addressing a plurality of cells within said semiconductor substrate (i) to apply a stimulus to each of said electrodes to activate a predetermined redox active moiety that is associated with an electrode, and (ii) to detect, by means of said electrodes, corresponding responses produced as a result of said activation of said redox active moieties, the magnitude of said corresponding responses indicating the presence or absence of said target molecule in said sample.
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Accused Products
Abstract
A method for detecting a target moiety is disclosed. In one embodiment, a plurality of electrodes supported by a semiconductor substrate are brought into proximity with a reaction medium comprising a sample suspected of containing the target molecule. Each of the electrodes comprises at least one target probe. A plurality of cells within the semiconductor substrate are selectively addressed to apply a stimulus to each of the electrodes to activate a predetermined redox active moiety that is associated with an electrode and to detect, by means of the electrodes, corresponding responses produced as a result of the activation of the redox active moieties. The magnitude of the corresponding responses indicates the presence or absence of the target molecule in the sample.
73 Citations
61 Claims
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1. A method for detecting a target molecule, said method comprising:
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(a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium comprising a sample suspected of containing said target molecule, each of said electrodes comprising at least one target probe, (b) selectively addressing a plurality of cells within said semiconductor substrate (i) to apply a stimulus to each of said electrodes to activate a predetermined redox active moiety that is associated with an electrode, and (ii) to detect, by means of said electrodes, corresponding responses produced as a result of said activation of said redox active moieties, the magnitude of said corresponding responses indicating the presence or absence of said target molecule in said sample. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. A method for detecting a target molecule, said method comprising:
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(a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium comprising a sample suspected of containing said target molecule, each of said electrodes comprising at least one target probe, (b) selectively applying electrical signals to each of said electrodes to activate a predetermined redox active moiety that is associated with an electrode, and (c) detecting, by means of said electrodes, corresponding electrical signals produced as a result of said activation of said redox active moieties, the magnitude of said corresponding electrical signals indicating the presence or absence of said target molecule in said sample. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method for detecting a target nucleic acid, said method comprising:
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(a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium comprising a sample suspected of containing said target molecule, each of said electrodes comprising at least one oligonucleotide probe, (b) sending an item of numerical data to each of a plurality of cells within said semiconductor substrate by means of a data bus, said item of numerical data participating in the selection of a voltage to be applied to said electrodes, (c) sending an address to address decoders on said semiconductor substrate, said address decoders being in communication with each of said cells, whereby electrical signals are selectively applied to each of said electrodes to activate a predetermined redox active moiety that is associated with an electrode, and (d) detecting, by means of said electrodes, corresponding electrical signals produced as a result of said activation of said redox active moieties, the magnitude of said corresponding electrical signals indicating the presence or absence of said target nucleic acid in said sample. - View Dependent Claims (23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
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35. A method for detecting a target nucleic acid, said method comprising:
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(a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium comprising a sample suspected of containing said target molecule, each of said electrodes comprising at least one oligonucleotide probe wherein each of said oligonucleotide probes comprises a redox active moiety, (b) sending an item of numerical data to storage means in each of a plurality of cells within said semiconductor substrate by means of a data bus, said item of numerical data participating in the selection of a voltage to be applied to said electrodes, (c) sending an address to address decoders on said semiconductor substrate, said address decoders being in communication with said storage means, whereby said item of numerical data is stored in said storage means and voltages are selectively applied to each of said electrodes to activate said redox active moieties, and (d) detecting, by means of said electrodes, corresponding current or difference in potential or a combination thereof produced as a result of said activation of said redox active moieties, the magnitude of said current or potential difference indicating the presence or absence of said target nucleic acid in said sample. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43)
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44. A method for detecting a target nucleic acid, said method comprising:
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(a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium comprising a sample suspected of containing said target molecule, each of said electrodes comprising at least one oligonucleotide probe, (b) conducting a polymerase extension reaction to incorporate in each of said oligonucleotide probes, to which a target nucleic acid is bound, a redox active moiety or precursor thereof, (c) sending an item of numerical data to storage means in each of a plurality of cells within said semiconductor substrate by means of a data bus, said item of numerical data participating in the selection of a voltage to be applied to said electrodes, (d) sending an address to address decoders on said semiconductor substrate, said address decoders being in communication with said storage means, whereby said item of numerical data is stored in said storage means and voltages are selectively applied to each of said electrodes to activate redox active moieties associated with said electrodes, and (e) detecting, by means of said electrodes, corresponding current or difference in potential or a combination thereof produced as a result of said activation of said redox active moieties, the magnitude of said current or potential difference indicating the presence or absence of said target nucleic acid in said sample. - View Dependent Claims (45, 46, 47, 48, 49, 50, 51, 52)
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53. A method for identifying target nucleic acids in a sample, which comprises:
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(a) applying said sample to a plurality of test sites, each of said test sites comprising an oligonucleotide probe attached to an electrode, each of said electrodes being part of a surface of an integrated circuit, each of said oligonucleotide probes being capable of specifically binding to a target nucleic acid molecular structure, such that each of said test sites has oligonucleotide probes which specifically bind to a different target molecular structure;
(b) incubating said sample on said test sites in the presence of a polymerase and nucleotide triphosphate analogs comprising a redox active moiety or a precursor thereof to extend each oligonucleotide probe, to which a target nucleic acid molecular structure is bound, and to associate said redox active moiety or precursor thereof with each extended oligonucleotide probe, to which a target nucleic acid molecular structure is bound, with the proviso that, when said nucleotide triphosphate analogs comprise a precursor, a binding partner for said precursor is added wherein said binding partner comprises a redox active moiety;
(c) applying a voltage to each of said test sites by means of circuitry associated with said integrated circuit, said voltage being sufficient to activate said redox active moiety associated with an electrode; and
(d) detecting by means of said integrated circuit a current or difference in potential or a combination thereof at each of said test sites, the magnitude of which is related to the presence of said target nucleic acids in said sample. - View Dependent Claims (54, 55, 56)
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57. A method of testing a sample for the presence of target nucleic acids, said method comprising:
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(a) applying said sample to an array of test sites in multiple locations on a surface of an integrated circuit, each site having oligonucleotide probes formed therein of known binding characteristics wherein the oligonucleotide probes in each test site differ from the oligonucleotide probes in other test sites in a known predetermined manner such that the test site location of oligonucleotide probes and their binding characteristics are known;
(b) treating each test site to which a target nucleic acid is bound, to extend the length of each oligonucleotide probe thereby incorporating an electronically responsive detector agent into each of said oligonucleotides;
(c) applying an electrical signal to each of said test sites by means of circuitry associated with said integrated circuit, said electrical signal being sufficient to activate said electronically responsive detector agent associated with an electrode; and
(d) detecting by means of said integrated circuit a change in electronic properties of the test sites resulting from the binding of target nucleic acid to lengthened oligonucleotide probes in the test sites by detection circuitry coupled to individual test sites to determine which target nucleic acid has bound to a test site;
whereby the presence of a multiplicity of different target nucleic acids in the sample is detected. - View Dependent Claims (58, 59)
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60. A device comprising:
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(a) a semiconductor substrate, (b) at least one surface having associated therewith a redox active moiety, (c) an electrode adjacent said surface and supported by said semiconductor substrate, (d) a cell within said semiconductor substrate, (e) a digital analog converter to which said electrode is electrically coupled, said digital analog converter being associated with said cell, (f) an address decoder in communication with said cell, (g) a data bus for delivering an item of numerical data to said cell, (h) an address bus for delivering an address to said address decoder, and (i) means for monitoring said surface. - View Dependent Claims (61)
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Specification