Arrays for detecting nucleic acids
AssigneeAffymetrix, Inc.
InventorsStephen P.A. Fodor, Dennis W. Solas, William J. Dower
Life of this patent
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Abstract
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.
Claims25
A composition comprising a plurality of positionally distinguishable sequence specific reagents attached to a solid substrate, which reagents are capable of specifically binding to a predetermined subunit sequence of a preselected multi-subunit length having at least three subunits, said reagents representing substantially all possible sequences of said preselected length.
A method for sequencing a segment of a polynucleotide comprising the steps of:
- a) combining:
- i) a substrate comprising a plurality of chemically synthesized and positionally distinguishable oligonucleotides capable of recognizing defined oligonucleotide sequences;
- and
- ii) a target polynucleotide;
- thereby forming high fidelity matched duplex structures of complementary subsequences of known sequence;
- and
- b) determining which of said reagents have specifically interacted with subsequences in said target polynucleotide.
A method for sequencing a polymer, said method comprising the steps of:
- a) preparing a plurality of reagents which each specifically bind to a subsequence of preselected length;
- b) positionally attaching each of said reagents to one or more solid phase substrates, thereby producing substrates of positionally definable sequence specific probes;
- c) combining said substrates with a target polymer whose sequence is to be determined;
- and
- d) determining which of said reagents have specifically interacted with subsequences in said target polymer.
A method of using a fluorescent nucleotide to detect interactions with oligonucleotide probes of known sequence, said method comprising:
- a) attaching said nucleotide to a target unknown polynucleotide sequence, and
- b) exposing said target polynucleotide sequence to a collection of positionally defined oligonucleotide probes of known sequences to determine the sequences of said probes which interact with said target.
A method of mapping a plurality of sequences relative to one another, said method comprising:
- a) preparing a substrate having a plurality of positionally attached sequence specific probes;
- b) exposing each of said sequences to said substrate, thereby determining the patterns of interaction between said sequence specific probes and said sequences;
- and
- c) determining the relative locations of said sequence specific probe interactions on said sequences to determine the overlaps and order of said sequences.
Dependencies are inferred from the claim text.