Methods to increase nucleotide signals by raman scattering

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

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C435S091200, C536S023100, C536S024300, C422S082080

Reexamination Certificate

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06972173

ABSTRACT:
The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid13. Exonuclease15treatment of the labeled nucleic acid13results in the release of labeled nucleotides16, 130, which are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides16, 130released from a nucleic acid13by exonuclease15treatment are covalently cross-linked to silver or gold nanoparticles140and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus10, 100, 210for nucleic acid sequencing.

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