The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, exonuclease treatment of the nucleic acids 109 results in the release of nucleotides 110. The nucleotides may pass from a reaction chamber 101 through a microfluidic channel 102 and enter a nanochannel or microchannel 103. The nanochannel or microchannel 103 may be packed with nanoparticle 111 aggregates containing hot spots for Raman detection. As the nucleotides 110 pass through the nanoparticle 111 hot spots, they may be detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Identification of the sequence of nucleotides 110 released from the nucleic acid 109 provides the nucleic acid sequence. Other embodiments of the invention concern apparatus 100 for nucleic acid sequencing.