Abstract: The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids.

Abstract: The invention provides nucleotide analogs and methods of using them in sequencing reactions.

Abstract: The invention provides methods for improving the accuracy of a sequencing-by-synthesis reaction by sequencing at least a portion of a template and at least a portion of template complementary sequence.

Abstract: The invention provides methods for sequencing a polynucleotide comprising stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or full completion.

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 nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: The invention provides methods and devices for high throughput single molecule sequencing of a plurality of target nucleic acids using a universal primer. Devices of the invention comprise a plurality of oligonucleotides, each having the same sequence, bound to a solid support, and ligated to a plurality of target nucleic acids.

Abstract: The disclosure provides nucleotide analogs and methods of their use. Analogs of the invention comprise a reporter molecule (label) attached via the N4, N6, O4, or O6 position of the nitrogenous base portion of the analog. In a preferred embodiment, nucleotide analogs of the invention comprise a label attached to the nitrogenous base portion of the analog via a cleavable linker at the N4, O4, N6 or O6 position.

Abstract: The invention provides molecules and methods for nucleic acid synthesis reactions useful in sequencing-by-synthesis processes.

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 present invention relates to apparatus, systems, and methods for analyzing biological samples. The apparatus, systems, and methods can involve using a vacuum source to pull microfluidic volumes through analytical equipment, such as flow cells and the like. Additionally, the invention involves using optical equipment in conjunction with the analytical equipment to analyze samples and control the operation thereof.

Abstract: The invention provides methods for improving the fidelity of a sequencing-by-synthesis reaction by resequencing at least a portion of a nucleic acid template.

Abstract: The invention provides a family of tethered 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 tethered nucleotide analogs.

Abstract: A apparatus and method for loading a sample into a microfluidic flow cell allows for more precise loading, reduced cross-contamination, and more efficient use of samples to be analyzed. The system for loading a sample into a flow cell includes a flow cell defining a plurality of individually isolated channels through which fluid can flow. The flow cell also defines an inlet port and an outlet port for each of the channels. The system also includes a base that defines a chamber for receiving the flow cell, a cover pivotally attached to the base, and a passive vacuum source for pulling a volume through the flow cell. The method of loading a sample includes inserting the flow cell into the sample loading apparatus, placing a sample in at least one of the wells of the loading block, activating a vacuum source fluidly coupled to the outlet ports to pull the sample into the channel, and optionally aspirating the unused sample from the well.

Abstract: A multi-channel flow cell can allow for reduced cross-contamination in sample loading and the ability to observe activity within the flow cell once the channels are loaded. A multi-channel flow cell includes a plurality of independently-addressable channels sandwiched between a two substrates. Each of the channels can be coated with a layer that facilitates support-binding of an analyte. Each of the channels terminates on one end in an inlet and on the other end in an outlet. A loading block having inlet ports that match the inlets of the channels can be mated to the inlets of the channels, and an outlet block can be mated to the outlets of the channels. Analytes can be introduced into the channels via the inlet ports of the loading block and are pulled through the channels by capillary action or by vacuum. Once analyte has been introduced into each of the channels, the loading and outlet blocks can be removed and the device turned over.

Abstract: A sample nucleic acid sequence is compared against a database to find a matching sequence. In one embodiment, this comparison is accomplished with a table look-up approach that involves using sequences with collapsed homopolymer regions.

Abstract: The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions.

Abstract: A method of increasing the spatial uniformity of the detected intensity of a beam of light from a laser in a system including the laser and a light detector. In one embodiment the method includes the steps of generating a beam of light with the laser; and moving the beam of light and the light detector relative to each other, such that the detector averages the spatial intensity of the beam of light over time. In another embodiment the invention relates to a system for increasing the detected spatial uniformity of the intensity of a beam of light. In one embodiment the system comprises a light detector; a laser source for generating the beam of light; and a means for moving the beam of light and the detector relative to one another such that the detector averages the intensity of the light beam over time.

Abstract: The invention provides compositions for improving the accuracy of a sequencing-by-synthesis reaction by minimizing the incorporation of unlabeled dNTPs.

Abstract: The invention provides a family of tethered 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 tethered nucleotide analogs.