Method for nucleic acid detection using voltage enhancement

摘要

Methods are provided for carrying out DNA sequencing on a device having upper and lower conductive layers separated by an insulative layer. Holes in the upper conductive layer create discrete attachment sites for DNA fragments. Voltage is applied to the surface to control affinity between the attachment sites and the DNA fragments, and to compact the DNA fragments for discrete optical detection.

主权项

1. A method of discrete analysis of individual nucleic acid constructs in an array, said method comprising:
(a) providing a device comprising a substrate comprising a surface and a plurality of nucleic acid macromolecules disposed on the surface at localized discrete attachment sites; (b) hybridizing a probe of known sequence having an optically detectable label to each of at least some of the nucleic acid macromolecules under conditions that permit formation of perfectly matched duplexes between the probe and complementary sequences in the nucleic acid macromolecules; (c) applying a positive charge to the substrate surface to promote compacting of the macromolecules for discrete optical detection; and (d) optically detecting the labeled duplexes while the positive voltage is applied, thereby identifying a nucleotide sequence in at least some of the nucleic acid macromolecules.