METHODS AND APPARATUS FOR MEASURING ANALYTES USING LARGE SCALE FET ARRAYS
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.
1 - 106 . (canceled)
107 . An apparatus comprising:
a sensor array of at least 10 3 sensors, wherein each sensor in the sensor array comprises a field-effect transistor; and
a plurality of microwells, wherein each microwell is disposed on at least one sensor.
108 . The apparatus of claim 107 , further comprising:
a control circuit coupled to the sensor array and configured to receive samples of one or more output signals from said field-effect transistors.
109 . The apparatus of claim 108 , wherein said sensors of said sensor array are arranged in rows and columns, and wherein said control circuit receives samples of said one or more output signals from sensors in multiple columns of a previously selected row during a bus settling time of a successively selected row.
110 . The apparatus of claim 108 , wherein said control circuit comprises an analog-to-digital circuit configured to convert samples of said one or more output signals to corresponding digital outputs.
111 . The apparatus of claim 108 , wherein each of said one or more output signals is a voltage signal measured in reference to a voltage of a reference electrode.
112 . The apparatus of claim 107 , wherein each of said sensors occupies an area on a semiconductor substrate of approximately ten micrometers by ten micrometers or less.
113 . The apparatus of claim 112 , wherein each of said sensors has a pitch of 10 μm or less.
114 . The apparatus of claim 107 , wherein each microwell is capable of containing at least one chemical reaction, and wherein said chemical reaction has a hydrogen ion concentration byproduct.
115 . The apparatus of claim 114 , wherein, an output signal of each of said sensors represents one or more changes in said hydrogen ion concentration within a range of pH 7 to pH 9.
116 . The apparatus of claim 107 , wherein each of said microwells has a volume in the range of 1 μm 3 to 1500 μm 3 .
117 . An apparatus comprising:
a sensor array of at least 10 3 sensors, wherein each sensor in the sensor array comprises a field-effect transistor having a floating gate with an analyte-sensitive passivation layer;
a plurality of microwells, wherein each microwell is capable of containing at least one chemical reaction and is disposed on at least one sensor; and
a control circuit coupled to the sensor array and configured to receive samples of one or more output signals from said field effect transistors.
118 . The apparatus of claim 117 , wherein each of said sensors occupies an area on a semiconductor substrate of approximately ten micrometers by ten micrometers or less.
119 . The apparatus of claim 118 , wherein each of said sensors has a pitch of 10 μm or less.
120 . The apparatus of claim 119 , wherein said chemical reaction has a hydrogen ion concentration byproduct.
121 . The apparatus of claim 120 , wherein said one or more output signals of each of said sensors represent changes in said hydrogen ion concentration within a range of pH 7 to pH 9.
122 . The apparatus of claim 117 , wherein each of said microwells has a volume in the range of 1 μm 3 to 1500 μm 3 .
123 . The apparatus of claim 117 , wherein said control circuit comprises an analog-to-digital circuit configured to convert samples of said one or more output signals to corresponding digital outputs.
124 . The apparatus of claim 117 , wherein each of said one or more output signals is a voltage signal measured in reference to a voltage of a reference electrode.
125 . A method comprising:
measuring one or more output signals from a sensor array of at least 10 3 sensors, wherein each sensor in the sensor array comprises a field-effect transistor and a microwell disposed thereon; and
converting said one or more output signals to corresponding digital outputs using an analog-to-digital circuit to sample said one or more output signals.
126 . The method of claim 125 , wherein each of said one or more output signals is a voltage signal, and wherein said measuring comprises measuring said one or more output signals in reference to a voltage of a reference electrode.
127 . The method of claim 125 , wherein said measuring comprises measuring a hydrogen ion concentration byproduct generated by a chemical reaction in each of the microwells.