Methods and apparatus for measuring analytes including chemical sensor array

Abstract

Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

What is claimed is: 
     
         1 . A system for chemical analysis comprising:
 an array of pixels having a plurality of rows and a plurality of columns, each of the pixels having a reaction area and a chemically sensitive sensor configured to provide an analog output indicative of the reactions sensed within the reaction area for the pixel;   a selection circuit arranged to select at least one of the rows;   a plurality of column circuits, each column circuit configured to receive the analog output from a selected row during a sampling period;   an analog to digital conversion circuit associated with each of the column circuits and configured to receive the analog output from the column circuits that were received by the column circuits during the sampling period and to sample them at a second rate that is greater than a first rate, such that a series of samples is made for each of the analog outputs at the second rate for a second sampling period that corresponds to the sampling period; and   an estimation device that receives that series of samples and determines an estimated pixel value from the series of samples during the sampling period.   
     
     
         2 . The system of  claim 1 , wherein the array is arranged to have multiple sections having rows and columns, each of the sections having being operatively connected to the selection circuitry and the plurality of column circuits. 
     
     
         3 . The system of  claim 1 , wherein the analog output changes gradually to reach a final pixel value during the sampling period as reactions within the reaction area are sensed by the chemically sensitive sensor and the estimated pixel value is an estimation of the final pixel value. 
     
     
         4 . The system of  claim 1 , further comprising a framing device that forms a frame from the estimated pixel values from at least a portion of the array of pixels I at a predetermined time period. 
     
     
         5 . The system of  claim 4 , further comprising a condensing device that takes a predetermined number of frames within the predetermined time period and reduces them to a reduced number of frames for the predetermined time period. 
     
     
         6 . The system of  claim 5 , wherein the reduced number of frames is created through averaging. 
     
     
         7 . The system of  claim 5 , further comprising a storage device for storing the reduced number of frames. 
     
     
         8 . The system of  claim 1 , wherein the chemically sensitive sensors are ion sensitive sensors. 
     
     
         9 . The system of  claim 1 , wherein the sampling period is a time period that is too short for an output signal from the chemical sensors to reach their final value. 
     
     
         10 . A method of determining pixel values comprising:
 providing an array of pixels arranged in a plurality of rows and a plurality of columns;   selecting at least one row of pixels to be read out of the array;   outputting pixel data for the at least one row onto a column bus at a first rate; and converting pixel data from the column bus at a second rate that is multiple times the first rate such that an oversampled pixel data set is made for each pixel readout.   
     
     
         11 . The method of  claim 10 , further comprising storing the oversampled pixel data to create a frame of pixel data and averaging the frame of pixel data to form an average frame of pixel data. 
     
     
         12 . The method of  claim 11 , further comprising repeating the method for each remaining row in the plurality of rows to create a series of frames. 
     
     
         13 . The methods of  claim 12 , wherein the series of frames are averaged into a final frame.