Abstract: Provided are methods and systems for detecting formation of nucleotide-specific ternary complexes comprising a DNA polymerase, a nucleic acid, and a nucleotide complementary to the templated base of the primed template nucleic acid. The methods and systems facilitate determination of the next correct nucleotide without requiring chemical incorporation of the nucleotide into the primer. These results can even be achieved in procedures employing unlabeled, native nucleotides.

Abstract: Provided are sequencing-by-binding methods of detecting cognate nucleotides using a crippled DNA polymerizing enzyme that possesses the ability to bind the next correct nucleotide downstream of a primer in a template-dependent fashion, but does not possess the activity needed to promote phosphodiester bond formation. Use of the crippled DNA polymerase permits interrogation of one nucleotide at a time, without incorporation of any nucleotide. Labeled nucleotides, such as fluorescently labeled nucleotides, can be used in conjunction with the crippled DNA polymerase to establish cognate nucleotide identity in a rapid manner.

Abstract: Systems and methods for performing DNA sequencing. An example system includes a flow cell, a mechanism to generate fluid flow, a number of reservoirs for containing respective fluids, and a number valves configured such that fluid from any particular one of the plurality of reservoirs can be individually supplied to the flow cell under the impetus of the mechanism to generate fluid flow by opening of the respective valve of the particular reservoir and closing the other valves. Fluids containing test nucleotides may be sequentially flowed through the flow cell and the flow cell imaged at each step to detect binding of the test nucleotides to a sample. The nucleotide sequence of the sample is derived from the images. The sample may be arrayed on a sensing surface of a prism, and the images may be obtained, for example, by surface plasmon resonance imaging (SPRi) of the sensing surface or other techniques.

Abstract: Provided herein are methods for analyzing a signature sequence in a nucleic acid sample by rapid sequencing of a target nucleic acid region. The method examines the target nucleic acid directly and minimizes the number of examination steps needed to determine a signature that is characteristic of a genetic feature of the nucleic acid sample.

Abstract: The present disclosure provides compositions, methods and systems for sequencing a template nucleic acid using a polymerase based, nucleic acid binding reaction involving examination of the interaction between a polymerase and template nucleic acid in the presence of one or more unlabeled nucleotides. The methods rely, in part, on identifying a base of a template nucleic acid during nucleic acid synthesis by controlling the sequencing reaction conditions. Template nucleic acid bases may be identified during an examination step followed by an optional incorporation step.