Pacific Biosciences of California, Inc.

Advanced Micro Devices Corporation

Hal Computer Systems, Inc.

Fujitsu Corporation

Globalfoundries Inc.

Other

Pacific Biosciences, Inc.

Gene W Shen

Stephen T Yue

Lubomir Sebo

Andrei Fedorov

Louis Brogley

Michael C Shebanow

Yuri Lapin

Honey Osuna

Xiangxu Kong

John Lyle

Sean Lie

Jeremiah Hanes

Niteen Aravind Patkar

John R Szeto

Frank Zheng

Lei Sun

Wei-Chuan Sun

Natasha Popovich

Stephen Wilson Turner

Thang Pham

Michael Butler

Wei-Chuan (David) Sun

Robin A Emig

Paul S Peluso

Geoffrey Alan Otto

Farnad Sajjadian

Arkadusz Bibillo

Sophia Wu

Sunil Savkar

Stephan G Meier

Keith P Bjornson

Erik Miller

Satwik Kamtekar

Marius Evers

Jeffrey Wegener

Min Xu

Ashutosh Sham Dhodapkar

Paul S Keltcher

Robert Joseph Weber

Stephen P Dudek

Duc Do

Bruce R Holloway

S Craig Nelson

Ravi Swami

Michael A Simone

David Sun

Masahito Kubo

Hideki Osone

Zhong Wang

Takumi Maruyama

Grace Lee

Leslie A Barnes

Vipul Parikh

Murali V Krishna

Michael G Butler

Reaction mixtures are provided having at least a first reactant and a second reactant that produce signals in response to excitation illumination. The signals produced by the reactants have peaks at the same wavelengths, but have distinct signal intensities. In some embodiments, the reactants are FRET-labeled.

Methods of monitoring a reaction

Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.

Labeled nucleotide analogs, reaction mixtures, and methods and systems for sequencing

Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.

Protected fluorescent reagent compounds

Modified nucleotide reagents

Reaction mixtures are provided having at least a first nucleotide analog and a second nucleotide analog that produce signals in response to excitation illumination. The signals produced by the analogs have peaks at the same wavelengths, but have distinct signal intensities. The distinct intensities allow for identification of the analogs in nucleic acid sequencing. In some embodiments, FRET-labeled compounds are provided. In certain embodiments, FRET-labeled nucleotide analogs are used, for example, in DNA sequencing or RNA sequencing.

FRET-labeled compounds and uses therefor

The invention provides a novel class of cyanine dyes that are functionalized with sulfonic acid groups and a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.

Cyanine dyes

FRET-labeled compounds are provided for use in analytical reactions. In certain embodiments, FRET-labeled nucleotide analogs are used in place of naturally occurring nucleoside triphosphates or other analogs in analytical reactions comprising nucleic acids, for example, template-directed nucleic acid synthesis, DNA sequencing, RNA sequencing, single-base identification, hybridization, binding assays, and other analytical reactions.

Compositions, devices, systems and methods for increasing the signal to noise ratio (SNR) and/or enhancing photoprotection in an illuminated analytical reaction by addition of one or more signal detection assay (SDA)-enhancing agents to the reaction mixture.

Compounds and systems for improving signal detection

The present invention provides methods, compositions, and systems for distributing single polymerase molecules into array regions. In particular, the methods, compositions, and systems of the present invention result in a distribution of single polymerase molecules into array regions at a percentage that is larger than the percentage expected to be occupied under a Poisson distribution.

Methods and compositions for single molecule composition loading

Multimeric protected fluorescent reagents and their methods of synthesis are provided. The reagents are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The reagents contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements. The reagents also contain coupling elements connect monomeric compounds into multimeric forms, thereby increasing brightness.

Multimeric protected fluorescent reagents

Growing community of inventors

Mountain View, CA, United States of America

Gene W Shen