Sensor arrays and nucleic acid sequencing applications

A method for sequencing DNA, comprising,

• providing an array comprised of a plurality of cavities to hold reactants, the cavities having a surface for attachment of DNA and coupled electronic sensors for detecting chemical reaction product changes in a solution, wherein each cavity is coupled to an electronic sensor;
• attaching DNA molecules to be sequenced to the surfaces of the cavities so that statistically only one DNA molecule to be sequenced is attached in each cavity;
• hybridizing a DNA oligo to each of the DNA molecules to be sequenced, the DNA oligo comprising at its 3′-end a first nuclease-resistant nucleotide or a first nuclease-resistant nucleotide analog;
• providing a first set of reactants to the cavities, the reactants comprising:
• nucleotides comprising only one type of nucleobases selected from the group consisting of adenine, cytosine, guanine, thymine and uracil;
• an enzyme capable of extending at least one DNA molecule, and
• an enzyme capable of deconstructing one or more nucleotides from at least one DNA molecule;
• wherein said providing reactants to the cavities is done under a condition that at the same time allows the DNA oligo to be extended by a nucleotide that is complementary to a base of the DNA molecules to be sequenced, wherein the base is immediately upstream from the base of the DNA molecules complementary to the first nuclease-resistant nucleotide, and allows the nucleotide to be deconstructed from the DNA oligo;
• identifying the base by monitoring increases in products of extension and/or deconstruction with the electronic sensors in the cavities;
• attaching the DNA oligo with a second nuclease resistant nucleotide or a second nuclease-resistant nucleotide analog, that is complementary to the base;
• repeating said providing reactants to the cavities and determining the identity of the single nucleotide at least one more time;
• and
• determining sequence information for the DNA molecules to be sequenced based on increases in the products of extension and/or deconstruction monitored by the electronic sensors.