Patent ID: 7892739

Claim:
A method of determining the presence of a specific oligonucleotide in a sample comprising: (1) providing, a) a sample suspected of containing said oligonucleotide, b) a substrate, c) a first nucleic acid conjugate comprising: (i) at least a portion of a single-stranded nucleic acid, said portion having a first end and a second end and further comprising a nucleotide sequence complementary to said oligonucleotide, wherein said first end of said single-stranded portion is immobilized on said substrate, (ii) a distance marker, and (iii) a molecular handle, wherein said second end of said single-stranded portion is linked to said distance marker and to said molecular handle, d) an instrument configured to (i) exert a stretching force on said molecular handle, (ii) measure said force and (iii) measure a change in a distance between said substrate and said distance marker; (2) moving said molecular handle with said instrument under conditions such that said single-stranded nucleic acid is stretched, (3) measuring a first change in said distance between said substrate and said distance marker and said force associated therewith under the conditions defined in step (2), (4) contacting said sample and said nucleic acid conjugate under conditions such that said oligonucleotide hybridizes to said nucleic acid conjugate to create a second nucleic acid conjugate such that at least a portion of said second conjugate is a double-stranded nucleic acid, (5) moving said molecular handle with said instrument under conditions such that said double-stranded nucleic acid is stretched, (6) measuring a second change in said distance between said substrate and said distance marker and said force associated therewith under the conditions defined in step (5), and (7) correlating said measured forces and changes in distances to a presence of said oligonucleotide in said sample.