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 the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.
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Citations
43 Claims
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1-23. -23. (canceled)
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24. An apparatus comprising:
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a substrate including an array of sensors; an array of wells disposed over the substrate, a well of the array of wells corresponding to a sensor of the array of sensors; and a cover disposed over the array of wells and defining a flow volume between the array of wells and the cover, the cover defining a fluid inlet and a fluid outlet in fluid communication with the flow volume, the cover including a non-flat wall defining a concave boundary of the flow volume, the non-flat wall having greater eccentricity at a first position in proximity to the fluid inlet than at a second position further from the fluid inlet. - View Dependent Claims (25, 26, 27, 28, 29, 30)
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31. A system comprising:
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a fluidic system including a fluid source; a computational system; and an apparatus comprising; a substrate including an array of sensors; an array of wells disposed over the substrate, a well of the array of wells corresponding to a sensor of the array of sensors; and a cover disposed over the array of wells and defining a flow volume between the array of wells and the cover, the cover defining a fluid inlet and a fluid outlet in fluid communication with the flow volume, the cover including a non-flat wall defining a concave boundary of the flow volume, the non-flat wall having greater eccentricity in proximity to the fluid inlet than at a second position further from the fluid inlet. - View Dependent Claims (32, 33, 34, 35, 36, 37)
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38. A method of sequencing a nucleic acid, the method comprising:
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flowing a reagent solution into a fluid inlet of an apparatus, the apparatus comprising; a substrate including an array of sensors; an array of wells disposed over the substrate, a well of the array of wells corresponding to a sensor of the array of sensors; and a cover disposed over the array of wells and defining a flow volume between the array of wells and the cover, the cover defining a fluid inlet and a fluid outlet in fluid communication with the flow volume, the cover including a non-flat wall defining a concave boundary of the flow volume, the non-flat wall having greater eccentricity in proximity to the fluid inlet than at a second position further from the fluid inlet; and measuring a signal from the sensor of the array of sensors. - View Dependent Claims (39, 40, 41, 42, 43)
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Specification