Single-molecule real-time sequencing

Single-molecule real-time (SMRT) sequencing is a parallelized single molecule DNA sequencing method. Single-molecule real-time sequencing utilizes a zero-mode waveguide (ZMW).[1] A single DNA polymerase enzyme is affixed at the bottom of a ZMW with a single molecule of DNA as a template. The ZMW is a structure that creates an illuminated observation volume that is small enough to observe only a single nucleotide of DNA being incorporated by DNA polymerase. Each of the four DNA bases is attached to one of four different fluorescent dyes. When a nucleotide is incorporated by the DNA polymerase, the fluorescent tag is cleaved off and diffuses out of the observation area of the ZMW where its fluorescence is no longer observable. A detector detects the fluorescent signal of the nucleotide incorporation, and the base call is made according to the corresponding fluorescence of the dye.[2]

  1. ^ Levene MJ, Korlach J, Turner SW, et al. (2003). "Zero-Mode Waveguides for Single-Molecule Analysis at High Concentrations". Science. 299 (5607): 682–6. Bibcode:2003Sci...299..682L. doi:10.1126/science.1079700. PMID 12560545. S2CID 6060239.
  2. ^ Eid J, Fehr A, Gray J, et al. (2009). "Real-Time DNA Sequencing from Single Polymerase Molecules". Science. 323 (5910): 133–8. Bibcode:2009Sci...323..133E. doi:10.1126/science.1162986. PMID 19023044. S2CID 54488479.