Affymetrix, Inc.

Affymax Technologies, N.v.

Other

Stephen P Fodor

Lubert Stryer

Richard P Rava

James L Winkler

Dennis Solas

Robert J Lipshutz

Michael C Pirrung

J Leighton Read

William J Dower

Christopher P Holmes

Mark O Trulson

Lois Aldwin

Christopher J Buchko

Debra A Ross

Mark S Chee

Glenn H McGall

Douglas N Modlin

David Stern

Peter J Fiekowsky

Edward L Sheldon

Ian Walton

Rolfe C Anderson

Martin J Goldberg

Earl A Hubbell

Maureen T Cronin

Peter E Lobban

Xiaohua C Huang

Virginia W Goss

R Fabian Pease

Macdonald S Morris

Thomas R Gingeras

Charles Garrett Miyada

MacDonald S Morris

Laura T Mazzola

Xiaohua X Huang

Earl A Hubble

A device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are delivered through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.

Combinatorial kit for polymer synthesis

The invention provides a method for analyzing the binding between a receptor and ligand using a probe array. The method generally involves contacting a labeled receptor with a substrate that includes a plurality of known locations to permit labeled receptor/ligand complexes to form. Intensity values based upon signal generated from bound labeled receptor are determined for a plurality of pixels within each of the known locations. A subset of pixels within each known location that fall within a statistical norm of intensity values for all the pixels within the known location is identified using a computer and then utilized to determine relative binding.

Methods for determining receptor-ligand binding using probe arrays

The present invention provides a miniaturized integrated nucleic acid diagnostic device and system. The device of the invention is generally capable of performing one or more sample acquisition and preparation operations, in combination with one or more sample analysis operations. For example, the device can integrate several or all of the operations involved in sample acquisition and storage, sample preparation and sample analysis, within a single integrated unit. The device is useful in a variety of applications, and most notably, nucleic acid based diagnostic applications and de novo sequencing applications.

Integrated nucleic acid diagnostic device

An array is created by moving a dispenser toward a solid support until a tip of the dispenser touches the support, withdrawing the tip from the surface and releasing a drop of 5 nanoliters or less in an area smaller than 1 mm.sup.2 to create an array of at least 100 spots.

Combinatorial strategies for polymer synthesis

The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the CFTR gene.

Arrays of nucleic acid probes and methods of using the same for

Labeled targets on a support synthesized with polymer sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, can be detected by exposing selected regions of sample 1500 to radiation from a source 1100 and detecting the emission therefrom, and repeating the steps of exposition and detection until the sample is completely examined.

Method and apparatus for imaging a sample on a device

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Method of Identifying a Base in a Nucleic Acid

The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Method of identifying nucleotide differences

Means for simultaneous parallel sequence analysis of a large number of biological polymer macromolecules. Apparatus and methods may use fluorescent labels in repetitive chemistry to determine terminal monomers on solid phase immobilized polymers. Reagents which specifically recognize terminal manomers are used to label polymers at defined positions on a solid substrate.

Analysis of surface immobilized polymers utilizing microfluorescence

A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Photolabile nucleoside protecting groups

A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are flowed through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.

Very large scale immobilized polymer synthesis using mechanically

Methods for concurrently processing multiple biological chip assays by providing a biological chip plate comprising a plurality of test wells, each test well having a biological chip having a molecular probe array; introducing samples into the test wells; subjecting the biological chip plate to manipulation by a fluid handling device that automatically performs steps to carry out reactions between target molecules in the samples and probes; and subjecting the biological chip plate to a biological chip plate reader that interrogates the probe arrays to detect any reactions between target molecules and probes.

Methods for concurrently processing multiple biological chip assays

Methods for nucleic acid analysis

The invention provides an array of oligonucleotide probes immobilized on a solid support for analysis of a target sequence from a human immunodeficiency virus. The array comprises at least four sets of oligonucleotide probes 9 to 21 nucleotides in length. A first probe set has a probe corresponding to each nucleotide in a reference sequence from a human immunodeficiency virus. A probe is related to its corresponding nucleotide by being exactly complementary to a subsequence of the reference sequence that includes the corresponding nucleotide. Thus, each probe has a position, designated an interrogation position, that is occupied by a complementary nucleotide to the corresponding nucleotide. The three additional probe sets each have a corresponding probe for each probe in the first probe set. Thus, for each nucleotide in the reference sequence, there are four corresponding probes, one from each of the probe sets. The three corresponding probes in the three additional probe sets are identical to the corresponding probe from the first probe or a subsequence thereof that includes the interrogation position, except that the interrogation position is occupied by a different nucleotide in each of the four corresponding probes.

Array of nucleic acid probes on biological chips for diagnosis of HIV

Growing community of inventors

Palo Alto, CA, United States of America

Stephen P Fodor