Abstract: Methods are described which enable higher signal/noise when performing surface measurements at the single molecule level. Methods are particularly useful in the field of molecular biology when performing single molecule nucleic acid sequencing by synthesis using dye labeled nucleotides. The method employs using a competitor molecule which blocks nonspecific binding of analog molecules to the surface.

Abstract: The invention provides methods for correcting misincorporation of a nucleotide in a primer during a sequencing-by-synthesis reaction by using both a polymerase substantially lacking in exonuclease activity and an enzyme, preferably a polymerase, having exonuclease activity.

Abstract: In one aspect the invention relates to an apparatus for analyzing the presence of a single molecule using total internal reflection. In one embodiment an apparatus for single molecule analysis includes a support having a sample located thereon; two sources of light at distinct wavelengths, a collimator for directing the light onto the sample through a total internal reflection objective; a receiver for receiving a fluorescent emission produced by a single molecule in the sample in response to the light; and a detector for detecting each of the wavelengths in the fluorescent emission. In another embodiment the apparatus further comprises a focusing laser for maintaining focus of the objective on the sample.

Abstract: In one aspect the invention relates to an apparatus for analyzing the presence of a single molecule using total internal reflection. In one embodiment an apparatus for single molecule analysis includes a support having a sample located thereon; two sources of light at distinct wavelengths, a collimator for directing the light onto the sample through a total internal reflection objective; a receiver for receiving a fluorescent emission produced by a single molecule in the sample in response to the light; and a detector for detecting each of the wavelengths in the fluorescent emission. In another embodiment the apparatus further comprises a focusing laser for maintaining focus of the objective on the sample.

Abstract: The invention provides methods for sequencing a nucleic acid comprising stabilizing a primer/target nucleic acid duplex on a substrate. Methods of the invention generally contemplate the use of a dual-anchored primer/target nucleic acid duplex, or a stabilizing molecule in a single molecule sequencing reaction.

Abstract: The invention provides methods for stabilizing a nucleic acid sequencing reaction. Generally, methods of the invention include exposing a target nucleic acid to a single-stranded nucleic acid binding protein and performing a sequencing reaction.

Abstract: The invention provides a family of nucleotide analogs useful in sequencing nucleic acids containing a homopolymer region comprising, for example, two or more base repeats, and to sequencing methods using such nucleotide analogs.

Abstract: The invention provides methods and apparatus for preparation and sequencing of nucleic acids.

Abstract: The invention relates to processes, compositions and kits for analysis of nucleic acid variations, especially single nucleotide polymorphisms (SNPs). An inventive process includes a procedure to enzymatically remove inorganic pyrophosphate from a sample prior to and/or during a single base extension reaction. Processes and compositions described herein are especially useful in nucleic acid analysis methods designed to minimize transfer and separation steps.

Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: In one aspect the invention relates to an apparatus for analyzing the presence of a single molecule using total internal reflection. In one embodiment an apparatus for single molecule analysis includes a support having a sample located thereon; two sources of light at distinct wavelengths, a collimator for directing the light onto the sample through a total internal reflection objective; a receiver for receiving a fluorescent emission produced by a single molecule in the sample in response to the light; and a detector for detecting each of the wavelengths in the fluorescent emission. In another embodiment the apparatus further comprises a focusing laser for maintaining focus of the objective on the sample.

Abstract: The invention relates to compositions and methods for a temporal signal pattern or signature representative of a characteristic of a nucleic acid template. The signature is created by monitoring the real time sequential pattern of signal emissions generated during nucleic acid template-dependent polymerization reactions.

Abstract: The invention provides methods for sequencing a nucleic acid comprising stabilizing a primer/target nucleic acid duplex on a substrate. Methods of the invention generally contemplate the use of a dual-anchored primer/target nucleic acid duplex, or a stabilizing molecule in a single molecule sequencing reaction.

Abstract: The present invention is directed toward improving the efficiency of chain terminator incorporation by Family B archaeon DNA polymerases. Previously, the low efficiency of ddNTP, and more especially dye-labeled ddNTP, incorporation has limited the usefulness of this group of DNA polymerases in protocols requiring chain terminator incorporation.

Abstract: The invention provides methods and compositions for improving the fidelity of a sequencing-by-synthesis reaction by using a nucleotide derivative that forms a hydrogen bond with a complementary nucleotide on a template, but fails to form a phosphodiester bond with the 3? hydroxyl group of a primer under conditions otherwise suitable for a polymerization reaction; thereby blocking incorporation of a mismatched nucleotide.

Abstract: The invention provides methods for correcting misincorporation of a nucleotide in a primer during a sequencing-by-synthesis reaction by using both a polymerase substantially lacking in exonuclease activity and an enzyme, preferably a polymerase, having exonuclease activity.

Abstract: The invention provides methods for sequencing a nucleic acid comprising stabilizing a primer/target nucleic acid duplex on a substrate. Methods of the invention generally contemplate the use of a dual-anchored primer/target nucleic acid duplex, or a stabilizing molecule in a single molecule sequencing reaction.

Abstract: The invention provides methods for sequencing a nucleic acid comprising conducting rolling circle amplification on a circular nucleic acid template, wherein the resulting amplicon is optionally anchored to a substrate in an individually optically resolvable manner, and performing a sequencing reaction.