Methods and apparatus for measuring analytes

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.

1 . A method for sequencing a nucleic acid comprising:
 contacting and incorporating known nucleotides into a plurality of identical nucleic acids in a reaction chamber in contact with or capacitively coupled to an ISFET, wherein the nucleic acids are covalently bound to a single bead in the reaction chamber, and   detecting hydrogen ions released upon nucleotide incorporation in the presence of no or limited buffering activity.   
     
     
         2 . The method of  claim 1 , wherein the ISFET is in an ISFET array that comprises 256 ISFET. 
     
     
         3 . The method of  claim 1 , wherein the reaction chamber comprises a solution having no buffer or low buffer concentration. 
     
     
         4 . The method of  claim 1 , wherein the reaction chamber comprises a solution having a buffering inhibitor. 
     
     
         5 . The method of  claim 1 , wherein the single bead is at least 90% saturated with nucleic acids. 
     
     
         6 . The method of  claim 1 , wherein the nucleic acids are sequencing primers. 
     
     
         7 . The method of  claim 6 , wherein the nucleic acids are hybridized to template nucleic acids. 
     
     
         8 . The method of  claim 6 , wherein the nucleic acids are hybridized to concatemers of identical template nucleic acids. 
     
     
         9 . The method of  claim 1 , wherein the nucleic acids are self-priming template nucleic acids. 
     
     
         10 .- 154 . (canceled)