Methods and apparatus for measuring analytes using large scale FET arrays
First Claim
1. An integrated circuit chip for determining byproducts of a plurality of extension reactions, the integrated circuit chip comprising:
- a sensor array of at least 105 sensors formed in a semiconductor substrate, each sensor of the array comprising a field-effect transistor having a threshold voltage and a floating gate with an analyte-sensitive passivation layer, the threshold voltage depending substantially on the analyte-sensitive passivation layer and trapped charge at the floating gate wherein the field-effect transistor is configured to provide at least one output signal dependent on the threshold voltage, and wherein the trapped charge of each floating gate is such that the threshold voltage is substantially the same for each sensor in response to the same amount of extension reaction byproduct proximate thereto;
a plurality of microwells disposed on the semiconductor substrate, each microwell capable of containing a separate extension reaction and being disposed on at least one sensor; and
control circuitry in the semiconductor substrate coupled to the sensor array to receive samples of the output signals from said field effect transistors at a rate of at least twenty frames per second so that the amounts of extension reaction byproducts are determined in each microwell by the output signal produced therefrom.
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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
17 Claims
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1. An integrated circuit chip for determining byproducts of a plurality of extension reactions, the integrated circuit chip comprising:
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a sensor array of at least 105 sensors formed in a semiconductor substrate, each sensor of the array comprising a field-effect transistor having a threshold voltage and a floating gate with an analyte-sensitive passivation layer, the threshold voltage depending substantially on the analyte-sensitive passivation layer and trapped charge at the floating gate wherein the field-effect transistor is configured to provide at least one output signal dependent on the threshold voltage, and wherein the trapped charge of each floating gate is such that the threshold voltage is substantially the same for each sensor in response to the same amount of extension reaction byproduct proximate thereto; a plurality of microwells disposed on the semiconductor substrate, each microwell capable of containing a separate extension reaction and being disposed on at least one sensor; and control circuitry in the semiconductor substrate coupled to the sensor array to receive samples of the output signals from said field effect transistors at a rate of at least twenty frames per second so that the amounts of extension reaction byproducts are determined in each microwell by the output signal produced therefrom. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. An integrated circuit chip for determining byproducts of a plurality of extension reactions, the integrated circuit chip comprising:
- a sensor array formed in a semiconductor substrate, each sensor of the array comprising a field-effect transistor having a floating gate and a threshold voltage, the threshold voltage depending on trapped charge of the floating gate, wherein the field-effect transistor is configured to provide at least one output signal dependent on the threshold voltage, and wherein the trapped charge of each floating gate is reduced so that the threshold voltage is substantially the same for each sensor in response to the same amount of extension reaction byproduct proximate thereto;
a plurality of microwells disposed on the semiconductor substrate, each microwell capable of containing a separate extension reaction and being disposed on at least one sensor; and
control circuitry in the semiconductor substrate coupled to the sensor array to receive samples of the output signals from said field effect transistors at a rate of at least one frame per second so that the amounts of extension reaction byproducts are determined in each microwell by the output signal produced therefrom, wherein said sensors of said sensor array are arranged in rows and columns and wherein said control circuitry successively receives samples of Output signals from sensors from multiple columns of a previously selected row during a bus settling time of a successively selected row, wherein said sensor array has at least 103 of said sensors. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17)
- a sensor array formed in a semiconductor substrate, each sensor of the array comprising a field-effect transistor having a floating gate and a threshold voltage, the threshold voltage depending on trapped charge of the floating gate, wherein the field-effect transistor is configured to provide at least one output signal dependent on the threshold voltage, and wherein the trapped charge of each floating gate is reduced so that the threshold voltage is substantially the same for each sensor in response to the same amount of extension reaction byproduct proximate thereto;
Specification