Applera Corporation

Roche Sequencing Solutions, Inc.

Applied Biosystems, LLC

Life Technologies Corporation

Pe Corporation (ny)

Roche Diagnostics Gmbh

F. Hoffmann-la Roche Ag

Meng Taing

Steven Menchen

Barnett B Rosenblum

Shaheer Khan

Peter Crisalli

Linda G Lee

Frank Bergmann

Omid Khakshoor

Scott C Benson

Daqing Sun

Dmitriy Gremyachinskiy

Dieter Heindl

Charles Stuart Vann

Christoph Seidel

Joe Y L Lam

Aruna Ayer

Christina E Inman

Weiguo Zhen

Aldrich N K Lau

Handong Li

Charles R Connell

George A Fry

Hannes Kuchelmeister

Khai Luong

Dieter Hiendl

Sara Kelley

Lars Hillringhaus

Seong-Ho Shin

Adolfo Vargas

Marshall W Porter

Rongxin Nie

The disclosure relates to tagged nucleoside compounds comprising a nucleotide polyphosphate covalently attached to a tag, wherein the compound is a polymerase substrate and the polymer moiety is capable of entering a nanopore linked to the polymerase and thereby altering the flow of ions through the nanopore. The disclosure also provides methods for preparing the tagged nucleoside compounds and for their use as tags in nanopore-based nucleic acid detection and sequencing.

Tagged nucleoside compounds useful for nanopore detection

The present disclosure provides 3' protected nucleotides, including those 3&#x2032; protected nucleotides having a detectable tag. Systems and methods of sequencing nucleic acids using the 3&#x2032; protected nucleotides are also disclosed, such as the sequencing of a nucleic acid using a nanopore or the sequencing of a nucleic acid via sequencing-by-synthesis.

3' protected nucleotides

The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5'-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

Tagged multi-nucleotides useful for nucleic acid sequencing

Intermediates and methods for forming activated metal complexes bound to surfaces on oxide layers, immobilizing beads to the modified surface and articles produced thereby are described. Hydroxyl groups on the oxide surfaces are reacted with a metal reagent complex of the formula Y(L-Pol), where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and 'Pol' represents a passivating agent such as a methoxyethanol, a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a plurality of functional groups that are reactive with or that form complexes with Y. The metal oxide surfaces exhibit minimal binding to bio-molecules, exhibit uniform deposition and immobilization of beads at high density, can be subsequently modified to create surfaces having a variety of properties, and can be used for nucleic acid sequencing and other analyses and in single-molecule detection schemes.

Deposition of metal oxides onto surfaces as an immobilization vehicle for carboxylated or phophated particles or polymers

Intermediates and methods for forming passivated surfaces on oxide layers and articles produced thereby are described. Hydroxyl or hydroxide groups on the oxide surfaces are reacted with a metal reagent of the formula Y(L-Pol), where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and 'Pol' represents a passivating agent such as a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a polyvalent reagent comprising a passivating moiety and a plurality of functional groups that are reactive with or that form complexes with Y. The passivating agent can also include a functional group such as biotin to provide surfaces with a desired functionality. The passivated surfaces exhibit minimal binding to bio-molecules and can be used in single-molecule detection schemes.

Intermediates and methods for forming passivated surfaces on oxide layers and articles produced thereby

Provided are nucleotide-dye conjugates and related compounds in which a dye is linked to a nucleobase directly or indirectly by an anionic linker. The anionic character of the linker is provided by one or more anionic moieties which are present in the linker, such as phosphate, phosphonate, sulfonate, and carboxylate groups. When the dye is a provided as a donor/acceptor dye pair, the anionic linker can be located between the donor and the acceptor, or between the nucleobase and either the donor or acceptor, or both. In one embodiment, conjugates of the invention provide enhanced electrophoretic mobility characteristics to sequencing fragments, e.g., for dideoxy sequencing using labeled terminators.

Fluorescent nucleobase conjugates having anionic linkers

Beads coded with phosphor particles and methods of making and using them are provided.

Phosphor particle coded beads

Atropisomeric energy-transfer dye compounds are disclosed. A variety of molecular biology applications utilize atropisomeric xanthene fluorescent dyes as labels for substrates such as nucleotides, nucleosides, polynucleotides, polypeptides and carbohydrates. Methods include DNA sequencing, DNA fragment analysis, PCR, SNP analysis, oligonucleotide ligation, amplification, minisequencing, and primer extension.

Atropisomers of asymmetric xanthene fluorescent dyes and methods of DNA sequencing and fragment analysis

Sulfonated diarylrhodamine compounds are useful as fluorescent labels of nucleosides, nucleotides, polynucleotides, and polypeptides. The compounds find particular application in the area of fluorescent nucleic acid analysis, e.g., automated DNA sequencing and fragment analysis, detection of probe hybridization in hybridization arrays, detection of nucleic acid amplification products, and the like.

Sulfonated diarylrhodamine dyes

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Hayward, CA, United States of America

Meng Taing