Patent ID: 7276338

Claim:
A method of obtaining sequence information at N nucleobase positions of a single copy of a target oligonucleotide, the method comprising the steps of: a) exposing the target oligonucleotide to one or more copies of a test oligonucleotide of M potentially informative nucleobases, wherein (i) if N is less than 50, M is 2, 3, or 4; (ii) if N is 50-99, M is 3, 4, or 5; (iii) if N is 100-999, M is 4, 5, or 6; (iv) if N is 1,000-10,000, M is 5, 6, 7, or 8; and (v) if N is greater than 10,000, M is 7, 8, 9, 10, 11, 12, or 13; b) measuring the hybridization of the test oligonucleotide to the target oligonucleotide, thereby completing a first hybridization trial; c) dehybridizing the test oligonucleotide; d) exposing the target oligonucleotide to one or more copies of at least one additional test oligonucleotide of M potentially informative nucleobases; e) measuring the hybridization of the additional test oligonucleotide to the target oligonucleotide, thereby completing a further hybridization trial; and f) repeating steps c) to e) until the information content from the hybridization trials exceeds the information content of the target oligonucleotide, wherein the information content from a single hybridization trial is I ⁡ ( M , N ) = Log 2 ⁡ ( 1 P ⁡ ( M , N ) ) ⁢ P ⁡ ( M , N ) + Log 2 ⁡ ( 1 1 - P ⁡ ( M , N ) ) ⁢ ( 1 - P ⁡ ( M , N ) ) where P(M,N) is the probability that the M potentially informative nucleobases fully hybridize with a given target oligonucleotide of N nucleobases.