Curagen Corporation

454 Life Sciences Corporation

Joel S Bader

Jonathan Marc Rothberg

John W Simpson

Jan Berka

Keith McDade

Scott B Dewell

Christopher M Colangelo

Gregory T Went

Michael W Deem

Gregory T Mulhern

Yi Liu

Michael Weiner

Jonathan M Rothberg

Steven A Henck

Darius M Dziuda

Thomas P Jarvie

Jane Berka

Michael Philip Weiner

Disclosed herein are methods and apparatuses for sequencing a nucleic acid. These methods permit a very large number of independent sequencing reactions to be arrayed in parallel, permitting simultaneous sequencing of a very large number (&#x3e;10,000) of different oligonucleotides.

Apparatus and method for sequencing a nucleic acid

Method of sequencing a nucleic acid

Disclosed herein are methods and apparatuses for sequencing a nucleic acid. In one aspect, the method includes annealing a population of circular nucleic acid molecules to a plurality of anchor primers linked to a solid support, and amplifying those members of the population of circular nucleic acid molecules which anneal to the target nucleic acid, and then sequencing the amplified molecules by detecting the presence of a sequence byproduct such as pyrophosphate.

The present invention provides novel methods to identify, classify, quantify and compare nucleic acids and polypeptides.

Methods for classifying nucleic acids and polypeptides

Disclosed herein are methods and apparatuses for sequencing a nucleic acid. The method includes annealing a population of circular nucleic acid molecules to a plurality of anchor primers linked to a solid support, and amplifying those members of the population of circular nucleic acid molecules which anneal to the target nucleic acid, and then sequencing the amplified molecules by detecting the presence of a sequence byproduct.

This invention relates to a method and device for separating charged particles according to their diffusivities in a separation medium by means of a spatially and temporally varying electric potential. The method is particularly suited to sizing and separating DNA fragments, to generating DNA fragment length polymorphism patterns, and to sequencing DNA through the separation of DNA sequencing reaction products. The method takes advantage of the transport of charged particles subject to an electric potential that is cycled between an off-state (in which the potential is flat) and one or more on-states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary potential wells. The potential wells are at constant spatial positions in the on-state. Differences in liquid-phase diffusivities lead to charged particle separation. A preferred embodiment of the device is microfabricated. A separation medium fills physically defined separation lanes in the device. Electrodes deposited substantially transverse to the lanes create the required electric potentials. Advantageously, injection ports allow sample loading, and special gating electrodes focus the sample prior to separation. The effects of thermal gradients are minimized by placing the device in contact with a thermal control module, preferably a plurality of Peltier-effect heat transfer devices. The small size of a microfabricated device permits rapid separation in a plurality of separation lanes.

Separation of charged particles by a spatially and temporally varying electric field

This invention includes methods for analyzing data generated by various solid-state NMR experiments, including rotational echo double resonance (REDOR), transferred echo double resonance (TEDOR), dipolar recoupling at the magic angle (DRAMA), dipolar recoupling with a windowless sequence (DRAWS), and melding of spin-locking and DRAMA (MELODRAMA). The methods are based alternately on a new analytical transform or the maximum entropy method and their multi-dimensional extensions. They permit simultaneous, multiple distance measurements of high accuracy and precision, even from nuclei with identical chemical shifts. By providing high quality easily obtained distance measurement from disordered solid state materials, this invention also improves drug discovery and design through fast determination of structures of pharmaceutical lead compounds, drug molecules, or their targets.

Method for distance measurements with solid-state NMR

This invention relates to a method and device for separating charged particles according to their diffusivities in a separation medium by means of a spatially and temporarily varying electric potential. The method is particularly suited to sizing and separating DNA fragments, to generating DNA fragment length polymorphism patterns, and to sequencing DNA through the separation of DNA sequencing reaction products. The method takes advantage of the transport of charged particles subject to an electric potential that is cycled between an off-state (in which the potential is flat) and one or more on-states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary potential wells. The potential wells are at constant spatial positions in the on-state. Differences in liquid-phase diffusivities lead to charged particle separation. A preferred embodiment of the device is microfabricated. A separation medium fills physically defined separation lanes in the device. Electrodes deposited substantially transverse to the lanes create the required electric potentials. Advantageously, injection ports allow sample loading, and special gating electrodes focus the sample prior to separation. The effects of thermal gradients are minimized by placing the device in contact with a thermal control module, preferably a plurality of Peltier-effect heat transfer devices. The small size of a microfabricated device permits rapid separation in a plurality of separation lanes.

Growing community of inventors

Stamford, CT, United States of America

Joel S Bader