Abstract: An embodiment of a method for sequencing a species of nucleic acid template using pH inert reference sensors is described that comprises the steps of: introducing a nucleotide species to an array of wells where a plurality of the wells comprise a species of nucleic acid template and a plurality of the wells comprise a plurality of functional groups with a high pH buffering characteristic, and in at least a first well a polymerase species incorporates the nucleotide species into a plurality of strands complementary to the species of nucleic acid template disposed in the first well and results in a release of a plurality of hydrogen ions; detecting a signal in the first well that is responsive to the hydrogen ions and one or more noise sources; detecting a signal in a second well comprising the functional groups with the high pH buffering characteristic that is responsive to the one or more noise sources; and subtracting the second well signal from the first well signal to generate a corrected signal associated

Abstract: The present invention provides a nucleic acid that comprises a nucleic acid of SEQ ID NO: 1 or 3 encoding an Aae pyrophosphatase protein, an enzyme protein of SEQ ID NO: 2 or 4, and methods of sequencing using an isolated Aae pyrophosphatase protein.