Methods and apparatus for measuring analytes using large scale FET arrays
First Claim
1. A method for nucleic acid sequencing, the method comprising:
- disposing at least one template nucleic acid in a reaction chamber communicating with a chemical sensor;
introducing known nucleotides into the reaction chamber;
detecting an output pulse from the chemical sensor indicating an end of an incorporation interval of the known nucleotides into the template nucleic acid; and
determining a number of known nucleotides incorporated during the incorporation interval based on a time interval between the introduction of the known nucleotides and the detection of the output pulse.
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Abstract
Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.
386 Citations
20 Claims
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1. A method for nucleic acid sequencing, the method comprising:
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disposing at least one template nucleic acid in a reaction chamber communicating with a chemical sensor; introducing known nucleotides into the reaction chamber; detecting an output pulse from the chemical sensor indicating an end of an incorporation interval of the known nucleotides into the template nucleic acid; and determining a number of known nucleotides incorporated during the incorporation interval based on a time interval between the introduction of the known nucleotides and the detection of the output pulse. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A method for nucleic acid sequencing, the method comprising:
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disposing at least one template nucleic acid in a reaction chamber communicating with a chemical sensor; introducing known nucleotides into the reaction chamber; detecting a first output pulse from the chemical sensor indicating a beginning of incorporation events of the known nucleotides into the template nucleic acid; detecting a second output pulse from the chemical sensor indicating an end of incorporation events of the known nucleotides into the template nucleic acid; and determining a number of known nucleotides incorporated into the at least one template nucleic acid based on a time interval between the detection of the first output pulse and the detection of the second output pulse. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18)
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19. A method for nucleic acid sequencing, the method comprising:
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disposing at least one template nucleic acid in a reaction chamber communicating with a chemical sensor; introducing known nucleotides into the reaction chamber; and detecting incorporation of at least one of the known nucleotides into the at least one template nucleic acid by receiving a pair of output pulses from the chemical sensor in response to introducing the known nucleotides. - View Dependent Claims (20)
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Specification