Methods and Apparatus for Measuring Analytes Using Large Scale FET Arrays
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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 hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.
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Citations
130 Claims
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1-106. -106. (canceled)
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107. A method of sequencing a plurality of template nucleic acids comprising:
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a) disposing a plurality of template nucleic acids in reaction chambers, wherein the reaction chambers are coupled to at least one field effect transistor (FET) comprising a floating gate and a dielectric layer;
wherein the reaction chambers further contains multiple copies of a respective template nucleic acids which remain substantially uncoupled from the reaction chamber;b) exposing the template nucleic acids to a known nucleotide and a polymerase; c) detecting a signal output in the FET in response to incorporation of the nucleotide; d) repeating steps (b) and (c) with additional known nucleotides. - View Dependent Claims (108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120)
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121. A method of sequencing a plurality of template nucleic acids comprising:
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a) disposing a plurality of template nucleic acids in reaction chambers, wherein the reaction chambers are coupled to at least one field effect transistor (FET);
wherein the reaction chambers further contains multiple copies of a respective template nucleic acids;b) exposing the template nucleic acids to a known nucleotide and an enzyme; c) detecting a signal output in the FET in response to incorporation of the known nucleotide, wherein said signal output results from a change in voltage relative to a fluidic electrode; d) repeating steps (b) and (c) with additional known nucleotides. - View Dependent Claims (122, 123, 124, 125, 126, 127, 128)
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129. An apparatus for sequencing a plurality of template nucleic acids comprising:
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a sensor array comprising a plurality of field effect transistors (FETs) coupled to a plurality of reaction chambers; a plurality of template nucleic acids present as multiple copies of a respective template nucleic acid disposed in a respective reaction chamber, each reaction chamber further containing a known nucleotide and an enzyme; and control circuitry that detects signals output in the plurality of FETs in response to incorporation of the known nucleotide by the enzyme into respective template nucleic acids. - View Dependent Claims (130)
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Specification