(Invited) DNA Sequencing with Carbon Nanotube Electronics

Nanoscale materials and devices provide new opportunities to monitor and understand biomolecules. This presentation will review novel devices in which single molecules of DNA polymerase have been joined to single-walled carbon nanotube (SWNT) transistors. DNA polymerases are the enzymes that convert single-stranded DNA into double-stranded helices. This biochemical process is the primary step in DNA replication, amplification, and most sequencing technologies. When one of these polymerases is attached to a SWNT transistor, the enzyme’s native activity is simultaneously transduced into a high-resolution electrical signal [1]. Each time the enzyme works its way down a DNA strand, it generates a nucleotide-by-nucleotide signal that encodes the DNA sequence. This hybrid, biofunctional device is the key element for developing a new, electronic DNA sequencing technology. As a solid-state, manufacturable element, the SWNT transistors provide exciting possibilities for high-density, high-throughput, and low cost sequencing solutions. In addition, the technique is easily generalized to DNA polymerases with specialized properties. Proof-of-principle measurements have been accomplished with DNA polymerases from five different organisms, including the highly processive polymerase of φ29 phage and the high-temperature polymerase Thermus aquaticus (Taq), which is the foundation of the polymerase chain reaction (PCR) and commercial DNA amplification. The SWNT transistor technique operates equally well at room temperature and the elevated PCR temperature of 72 °C, which opens opportunities for novel, high-temperature sequencing strategies with Taq or similar thermostable polymerases. [1] T. J. Olsen et. al., JACS 135, 7855 (2013); O. T. Gul et. al., Biosensors 6, 29 (2016)