Affymetrix, Inc.

Other

Chemistry & Technology for Genes, Inc.

Affyemtrix, Inc.

Nam Quoc Ngo

Glenn H McGall

Richard P Rava

Martin J Goldberg

Earl A Hubbell

Jennifer Dee Tan

Martin Diggelman

MacDonald S Morris

Laurent Jaquinod

Mel Yamamoto

Melvin Yamamoto

Anthony Dale Barone

Macdonald S Morris

Hong Wang

Glenn H Mc Gall

Evelyn Chai

The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Methods for photolithographic synthesis of polymer arrays utilizing anti-reflective coatings

Substrate preparation process

Methods using two to (n) purification columns to separate full length 5'-DMT-on oligonucleotides with size ranging from 40 to 180-mers from short length 5&#x2032;-DMT-on oligonucleotides. Two of the said methods require using some columns sequentially with the collection and reprocessing of an intermediate fraction and are used for oligonucleotides with length ranging from 70 to 180-mers. A third method is carried out with columns stacked and used in series and is best used to purify oligonucleotides with length ranging from 40 to 80-mers. In the presence of a high ionic strength buffer, the short length DMT-on oligonucleotides bind to the top stacked columns while the less hydrophobic contaminant or DMT-off failures do not bind and/or are being washed off. In a stacked configuration, the full length DMT-on oligonucleotides are retained by the bottom column while in a 15 sequential configuration, full length DMT-on oligonucleotides are collected and reprocessed.

Multi layer chromatography of nucleic acids

Cylindrical devices (frits) are prepared by embedding aminoalkyl- or mercaptoalkyl-modified Controlled Pore Glass (CPG) in high-density polyethylene. Methods and devices pertaining to their use in the synthesis of nucleic acids are described. A reusable synthesis column or a reusable 96-chamber synthesis plate have been designed to hold one to 96 of the said frits that are inserted reproducibly into the synthesis chambers with a frit insertor. A short gas surpressure is required to drive entry of chemical reagents into the said frit. Reagents are retained into the frit until a second, longer surpressure is applied to drain the said reagents.

Devices and methods for the synthesis of nucleic acids

The present invention relates to improved methods for the preparation of nucleic acids. More particularly, conventional solid supports used for nucleic acid synthesis are derivatized with activators having pKas within the 4 to 7 range. Preferentially, CPG-based solid supports are reacted with trialkoxysilanes containing an activator moiety such as pyridine. During each deblocking step of the nucleic acid synthesis cycle, bound pyridiniums are generated, yielding a weak acidic medium spreads throughout the solid support. The bound activators efficiently activate the phosphoramidite reagents towards coupling with 5'-hydroxynucleosides bound to the solid supports, thus eliminating or supplementing external deliveries of activator during the coupling steps.

Activator bound solid supports for nucleic acid synthesis via the phosphoramidite approach

VLSIPS&#x2122; manufacturing processes are of increasing commercial importance. The present invention provides methods and compositions for monitoring the efficiency and quality of polymer synthesis in VLSIPS&#x2122; arrays. Methods for monitoring polymer synthesis in an array on a substrate are provided. Monoisomeric labels for the labeling of synthetic polymer arrays are provided. Methods and compositions for post-synthetically labeling polymers in polymer arrays are also provided.

Methods and compositions for monitoring polymer array synthesis

The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Universal solid supports suitable for use synthesizing of oligonucleotides. The solid supports may be used irrespective of the first RNA or DNA nucleotide to be synthesized, and irrespective of the type of monomer reagent used during the synthesis, that is, irrespective of the type of substitution of the phosphate group in the 3&prime; position or in the 5&prime; position depending on whether the synthesis is carried out in the 5&prime; to 3&prime; or 3&prime; to 5&prime; direction. Following synthesis of the oligonucleotide, deprotection of protecting groups and cleavage of the oligonucleotide from the solid support is accomplished with treatment with standard basic media such as NH OH, NaOH, methylamine.

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Campbell, CA, United States of America

Nam Quoc Ngo