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 acid
13. Exonuclease 15 treatment of the labeled nucleic acid 13
results in the release of labeled nucleotides 16, 130, which are detected
by Raman spectroscopy. In alternative embodiments of the invention, nucleotides
16, 130 released from a nucleic acid 13 by exonuclease 15
treatment are covalently cross-linked to silver or gold nanoparticles 140
and 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 apparatus 10, 100, 210 for nucleic
acid sequencing.