Methods and apparatus for detecting molecular interactions using fet arrays

Abstract

Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. 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.

What is claimed: 
     
         1 . A method for identifying a sequence associated with a positive response to a particular active agent, comprising;
 sequencing a nucleic acid sequence from a first plurality of subjects that have exhibited a positive response and from a second plurality of subjects having a negative response to an active agent using one or more sequencing apparatuses, wherein each sequencing apparatus comprises an array of chemically-sensitive field effect transistors; and   identifying a common DNA sequence in the first plurality of subjects that have exhibited the positive response or from the second plurality of subjects that have exhibited the negative response that is not present in the first plurality of subjects.   
     
     
         2 . The method of  claim 1  wherein the first plurality of subjects and the second plurality of subjects are human subjects. 
     
     
         3 . The method of  claim 1  wherein the active agent is a therapeutic agent. 
     
     
         4 . The method of  claim 1 , wherein the nucleic acid sequence is a DNA sequence, and before sequencing, the method further comprises:
 preparing a plurality of nucleic acid sequences of a targeted size distribution for each DNA sample from the first plurality of subjects that have exhibited the positive response and from the second plurality of subjects having the negative response to the active agent.   
     
     
         5 . The method of  claim 4 , wherein the targeted size distribution is between 200 to 1000 base pairs in size. 
     
     
         6 . The method of  claim 4 , wherein the plurality of nucleic acid sequences is prepared using PCR-based amplification. 
     
     
         7 . The method of  claim 4 , further comprising:
 ligating adapter sequences on a 5′ and a 3′ end of each nucleic acid sequence of the plurality of nucleic acid sequences for each DNA sample; and   preparing a capture bead sample from the plurality of nucleic acid sequences for each DNA sample.   
     
     
         8 . The method of  claim 6 , wherein ligating adapter sequences includes providing a barcode for each nucleic acid sequence of the plurality of nucleic acid sequences for each DNA sample.