Agilent Technologies, Inc.

454 Life Sciences Corporation

Hewlett-packard Company

International Business Machines Corporation

Roche Molecular Systems, Inc.

Steven M Lefkowitz

Michel G M Perbost

Nelson R Holcomb

Carol T Schembri

Douglas J Dellinger

Roy H Kanemoto

Geraldine Fulcrand

Jonathan Marc Rothberg

John R Nobile

John Harris Leamon

Andreas N Dorsel

Michael Weiner

John W Sadler

Jan Berka

Yi-Ju Chen

Maithreyan Srinivasan

Kenton L Lohman

Vinod B Makhijani

Gary James Sarkis

Charles Z Hotz

Jonathan M Rothberg

Russell Alan Parker

Jong-Bum Kim

Daniel Bernardo Roitman

Yann A Astier

Nicholas Michael Sampas

Venkat K Balagurusamy

Paul K Wolber

Glenda Choate Delenstarr

Karen W Shannon

Patrick James Collins

George Roth

Kevin J Luebke

Leslie B Overman

Pengguang Yu

Namyong Kim

Jeffery R Sampson

Athene W C Chan

Disclosed are methods for nucleic acid amplification wherein nucleic acid templates, beads, and amplification reaction solution are emulsified and the nucleic acid templates are amplified to provide clonal copies of the nucleic acid templates attached to the beads. Also disclosed are kits and apparatuses for performing the methods of the invention.

Bead emulsion nucleic acid amplification

A nanopore device includes a multi-layer structure comprising a surface defining an aperture extending through the multi-layer structure, wherein at least the surface comprising a minimal diameter comprises a monosilane functionalized silicon dioxide having a silicon-oxygen-silicon bond, the monosilane functionalized silicon dioxide having the following structure: wherein n is an integer from 1 to 12; Rand Rare each independently a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or a tert-butyl group; and Ris a chloride, a carboxylic acid group, an amine group, an amide group, a thiol group, an alcohol group, an acyl chloride group, an acyl bromide group, an acyl iodide group, an alkene group, an alkyne group, or a polyether group. Also disclosed are methods for making, wetting, and operating the nanopore device.

Silicon oxide nanopore wetting and stabilization by molecular coating

The invention relates to a thin film coated array and the process of fabricating and using the array including methods of etching, depositing a thin film coating, preparing and using the thin film coated array.

Thin film coated microwell arrays

This invention relates to microwell array compositions which are coated with one or more thin film coatings. The invention includes the process of fabricating and using thin film coated microwell arrays.

Thin film coated microwell arrays and methods of using same

Methods, apparatus, and computer program products to form arrays of polymers each having a pattern of features on a surface of a flexible elongated web, comprising. In a method polymers or their precursor units are applied at an application station to the surface. Multiple features are covered at a reagent station with a continuous volume of reagent which chemically reacts with precursors or the web. The flexible elongated web is driven in a lengthwise direction through the application station. This sequence may be repeated as needed to form the arrays along the web. Also provided is a method preparing a surface of a flexible elongated web to receive a biopolymer array.

Chemical arrays

A method and apparatus for using arrays of polymers each having a pattern of features over a corresponding array region on a surface of a flexible elongated web. In this method each array region may be exposed to a corresponding continuous volume of a sample fluid. A method and apparatus are also provided for reading arrays disposed along a surface of a flexible elongated web. In one such method the web with the arrays thereon may be transported in a lengthwise direction past a reading location at which a characteristic of the features is read, while restraining the web on both surfaces on either side of the reading location to assist in maintaining the reading location flat.

Calibration devices for optical scanners and methods for their use are provided. The subject devices are characterized by having a polymeric coating with at least one fluorescent agent, where the devices have minimal local and global nonuniformities. The subject device may also include one or more photobleached regions. In using the subject devices, a surface is illuminated with at least one light source, fluorescence data is obtained from the surface and the optical system is calibrated based upon the obtained fluorescence data. The subject invention finds use in a variety of optical scanners, including biopolymeric array optical scanners. Also provided are kits for use in verifying and calibrating optical scanners.

Devices for calibrating optical scanners and methods of using the same

Methods for substantially improved detection and analysis in nucleic acid hybridization assays are described. The methods provide the reliable estimation of background signal which derives primarily from nonspecific hybridization. The invention is useful in chemical, biological, medical and diagnostic techniques, as well as for drug discovery.

Arrays comprising background features that provide for a measure of a non-specific binding and methods for using the same

Methods for stably associating a polyelectrolyte coating or film to a substrate surface, as well as the coated substrates produced thereby, are disclosed herein. In the subject methods, substrate surfaces are coated with a polyelectrolyte, and the coated substrate surfaces are treated with a bifunctional molecule under conditions sufficient to stably associate the film to the array surface. The subject methods find use in a variety of different applications, including the production of mircoarrarys.

Methods of making microarrays with substrate surfaces having covalently bound polyelectrolyte films

The invention provides a solid support for adsorbing a biomolecule. The support comprises a surface coating having a non-nucleotidic polymer tethered to a surface reactive site. The polymer comprises a backbone, terminus, and adsorbing moieties covalently attached to the backbone and capable of adsorbing a biomolecule that can assume a plurality of conformations. The polymer is generally tethered to the surface at its terminus and the backbone exhibits sufficient mobility and flexibility such that a biomolecule adsorbed by the adsorbing moieties can assume a desired conformation for hybridization. Also provided is a process for preparing a surface coating having a functionalized surface.

Surface with tethered polymeric species for binding biomolecules

A method of fabricating an array of biopolymers provides a shield for biochemical reactions and biochemical reactants and is particularly useful for those reactions and reactants that are susceptible to reaction with a component of the ambient environment during the fabrication of the array. The method is applicable to the conventional fabrication and synthesis methods used to fabricate a biopolymer array, such as in situ synthesis of biopolymers on an array and the attachment of pre-synthesized biopolymers on to an array. The method comprises applying a non-miscible fluid (NMF) to the array surface where the biopolymers are being synthesized or attached. The NMF is inert and insoluble with the biochemical reactants and other ancillary materials in solution used in conventional synthesis or attachment of biopolymers. The NMF provides a shield between the ambient atmosphere and the biopolymer synthesis materials or the deprotected pre-synthesized biopolymer at the surface of the array during the synthesis or attachment processes. The NMF may be applied as droplets over each feature location on the surface or may be applied by flooding the surface of the array to fully cover the features. Biomonomer or biopolymer solutions are deposited into or through the NMF to the feature locations on the surface of the array where the synthesis or attachment reactions are to take place using conventional deposition equipment to eject the solutions into the NMF. The NMF provides a shield for activated biomonomers that are susceptible to reaction with a component in the ambient environment, such as moisture in the air. Moreover, the NMF provides a shield for pre-synthesized biopolymers that are susceptible to evaporation when deprotected for attachment to the array surface. The method provides a means by which the potential reactivity of the activated biomonomer or deprotected biopolymer with an ambient atmosphere component can be kept low. As a result, biopolymer arrays can be more accurately fabricated.

Method of shielding biosynthesis reactions from the ambient environment on an array

A buffer composition, method and kit for hybridizing microarrays of nucleic acids bound to an adsorbed polymer surface of a siliceous substrate provide an envelope of conditions to hybridize nucleic acid targets, while preserving theintactness of the adsorbed polymer surface of the array. The buffer composition comprises a non-chelating buffering agent, a pH within a range of pH 6.4 and 7.5, a monovalent cation having a monovalent cation concentration that ranges from about 0.01 M to about 2.0 M, and optionally relatively lower concentrations of a chelating agent and an ionic surfactant. The total cation concentration of the buffer composition ranges from about 0.02 M to about 2.0 M. The method comprises incubating the targets with the microarray in the buffer composition at a temperature between about 55&deg; C. and 70&deg; C.

Buffer composition and method for hybridization of microarrays on adsorbed polymer siliceous surfaces

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Millbrae, CA, United States of America

Steven M Lefkowitz