Agilent Technologies, Inc.

University of Michigan

University of Houston System

Eric M Leproust

Xiaolian Gao

Xiaochuan Zhou

Hua Zhang

Jean Philippe Pellois

Qin Xiang

Paul K Wolber

Mel N Kronick

Peilin Yu

Douglas A Amorese

Bill J Peck

Glenda Choate Delenstarr

Jay K Bass

Michel G M Perbost

Theodore R Sana

Maryam Mobed-Miremadi

Peillin Yu

Robert Gellibolian

John Frederick Corson

Michael P Caren

Jayati Ghosh

Robert H Kincaid

Patrick James Collins

Charles David Troup

David L Hirschberg

Roy H Kanemoto

Xiangyang Zhou

Richard O Hilson

Michael G Booth

Diane Ilsley-Tyree

Andrew S Atwell

Lalitha Reddy

Michelle M Maranowski

Methods and compositions for generating mixtures of product molecules from an initial chemical array are provided. In the subject methods, a chemical array of surface immobilized first moieties is subjected to cleavage conditions such that a composition of solution phase first moieties is produced. The resultant composition of solution phase first moieties is then contacted with one or more reactants to produce a mixture of product molecules that are different from the first moieties. Also provided are the arrays employed in the subject methods and kits for practicing the subject methods.

Chemical arrays and methods of using the same

A method of modulation of synthesis capacity on and cleavage properties of synthetic oligomers from solid support is described. The method utilizes linker molecules attached to a solid surface and co-coupling agents that have similar reactivities to the coupling compounds with the surface functional groups. The preferred linker molecules provide an increased density of polymers and more resistance to cleavage from the support surface. The method is particularly useful for synthesis of oligonucleotides, oligonucleotides microarrays, peptides, and peptide microarrays. The stable linkers are also coupled to anchor molecules for synthesis of DNA oligonucleotides using on support purification, eliminating time-consuming chromatography and metal cation presence. Oligonucleotides thus obtained can be directly used for mass analysis, DNA amplification and ligation, hybridization, and many other applications.

Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid supports

Provided are improved processes and apparatuses for solid phase oligonucleotide synthesis, the improvements comprising carrying out detritylation of the nascent oligonucleotide using a composition of an organic solvent, a protic solvent and a selected concentration, or selected concentration range, of water. In some embodiments, an oligonucleotide synthesis apparatus includes means for adding water to a detritylation reagent. In some embodiments, an apparatus can include a water detector for analyzing the water concentration of a detritylation reagent to be reacted with a nascent oligonucleotide. An apparatus can comprise a feedback loop to control the concentration of water at the point of the detritylation reaction and/or to control the detritylation reaction time. The apparatuses and methods reduce batch-to-batch variations in the manufacture of oligonucleotides immobilized on the surface of various substrates.

Apparatuses and methods for oligonucleotide preparation

A method for controlling the use of oligonucleotide sequences released from arrays, comprises synthesizing a chemical array of oligonucleotides on a substrate under conditions for producing an array of cleavable oligonucleotides that are blocked from enzymatic reactions after cleavage. Methods may also include receiving a chemical array of cleavable oligonucleotides on a substrate, and cleaving the oligonucleotides from the array, wherein the oligonucleotides are blocked from enzymatic reactions after cleavage. Arrays, populations of oligonucleotides and kits are also provided to facilitate the methods.

Controlling use of oligonucleotide sequences released from arrays

Methods and devices for producing a nucleic acid arrays using in situ nucleic acid array synthesis protocols are provided. A feature of certain embodiments of the invention is that control probes are produced in collections of features, e.g., columns, of the arrays that have been selected according to a particular efficient control probe feature/column selection protocol. A feature of certain other embodiments of the invention is that an 'all-bases-all-layers' probe set is produced in at least one of column of the arrays. Also provided are devices configured for use in the subject methods, as well as arrays produced using the subject methods and devices as well as methods for using such arrays.

Nucleic acid array in situ fabrication methods and arrays produced using the same

Methods and apparatus are disclosed for synthesizing a plurality of biopolymers at predetermined feature locations on a surface of a substrate. One or more of the feature locations comprises degenerate biopolymers. One or more biopolymer subunit precursors are added, in multiple rounds of subunit additions, at each of multiple feature locations on the surface to form the plurality of biopolymers on the surface. For each feature location comprising degenerate biopolymers, the biopolymer subunit precursors comprise a mixture of biopolymer subunit precursors for forming the degenerate biopolymers at the feature location.

Methods and apparatus for preparing arrays comprising features having degenerate biopolymers

A method and system for quantifying and correcting spatial-intensity trends for each channel of a microarray data set having one or more channels. The method and system of one embodiment of the present invention selects a set of features from each channel of the microarray data set. Based on the selected set of features, a surface is used to determine the intensities for all features in each channel of the microarray data set. Spatial-intensity trends within the microarray data set are quantified, based on the surface to the intensities for each channel of the microarray data set. After the surface has been determined, the spatial-intensity trend can be removed from the microarray data set.

Method and system for quantifying and removing spatial-intensity trends in microarray data

Methods and devices for producing a polymer at a location of a substrate are provided. In the subject methods, a fluid droplet containing a first monomer labeled with a first detectable label is deposited from a fluid deposition device onto a location of a substrate surface having a second monomer labeled with a second detectable label. The first and second detectable labels are then detected to determine any misalignment between the fluid deposition device and the location of the substrate surface during deposition. Also provided are algorithms that perform the subject methods, as well as fluid deposition devices that include the subject algorithms. The subject invention also includes arrays produced according to the subject methods and kits that include the subject arrays.

Methods and devices for producing a polymer at a location of a substrate

The invention provides a method and apparatus for micro array fabrication exclusive from the impact of a gas. A housing with a gas free chamber provides for improved micro array fabrication with a lower defect rate. The invention provides a housing that excludes a gas such as ozone to prevent interaction with probe construction or attachment. A method of fabricating a micro array in an ozone free environment is also disclosed.

Method and apparatus for microarray fabrication

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San Jose, CA, United States of America

Eric M Leproust