Other

Genomics Usa, Inc.

Sergy Lemeshko

Michael E Hogan

Yuri Belosludtsev

Rahul Mitra

Joseph G Utermohlen

Frederick H Eggers

Tom Powdrill

Thomas F Powdrill

Provided herein are biomolecular hybridization devices comprising a substrate with a permanently and covalently attached surface of functional groups and an adsorbed monolayer of unmodified, single-stranded oligonucleotides all of which are 10 to about 24 bases in length as a saturated film of constrained oligonucleotides on the surface via direct non-covalent phosphate-surface adsorptive contact of substantially all phosphate groups of each oligonucleotide. The constrained oligonucleotides are effective to dissociably hybridize to a complementary single-stranded nucleic acid with asymmetric, non-helical base pairing and without oligonucleotide dissociation from the surface of the device. Also, provided are methods for hybridizing solution-state target nucleic acids to probe nucleic acids and for identifying a nucleotide sequence to which a nucleotide-binding protein binds using the biomolecular hybridization devices.

Methods and devices based upon a novel form of nucleic acid duplex on a surface

The present invention relates to simple method to fabricate DNA hybridization devices based upon adsorptive attachment of oligonucleotides to a positively charged surface. Such adsorbed oligonucleotide probes form a densely packed monolayer, which retains capacity for base-pair specific hybridization with a solution state nucleic acid target strand to form the duplex. However, both strand dissociation kinetics and the rate of DNase digestion suggest on symmetry grounds that solution-state nucleic acid binds to such adsorbed oligonucleotides to form a highly asymmetric and unwound duplex, with structural details that are substantially different from that known for the Watson-Crick DNA duplex. This novel nucleic acid duplex form can serve as the basis for a new class of hybridization device and methods for their use. It is also disclosed that new methods of nucleic acid duplex detection can be developed which are based upon the interaction of enzymes and dye labels with the unique structural characteristics of the non-helical duplex described herein. Preferred implementations of the invention include DNA microarrays, bead-based nucleic acid analysis, microelectronic devices to detect nucleic acid hybridization and more traditional methods of laboratory analysis, including hybridization on membranous and other solid supports.

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Houston, TX, United States of America

Sergy Lemeshko