(229ao) Quantum Molecular-Sequencing (QM-Seq): Single Molecule DNA and RNA Sequencing

Nagpal, P., University of Colorado Boulder
Chatterjee, A., University of Colorado Boulder

The sequences and structure of nucleic acids in bio-macromolecules like DNA and RNA can define their biological function by controlling the downstream expression of genes, proteins, and other cell-regulatory functions. Small variations in this genetic coding in individual cells can lead to mutations, which can play a key role in physiology. For example, recent data on genetic variation in Ebola virus through its origin and transmission provides valuable information about mutations that altered protein sequences, and new targets for diagnosis, vaccines and therapy. While nanoelectronic sequencing techniques can in-principle be used to distinguish biochemically distinct nucleobases, it relies on identifying unique â??electronic fingerprintsâ? for different nucleotides. So far only partial deoxynucleotides have been successfully identified for single molecule, in part due to the large conformational entropy of molecules which causes dispersion of electronic spectroscopic signatures. Furthermore, attempts at using magnitude of electronic current, current decay properties, and its derivative (dI/dV) have been unable to provide deterministically unique fingerprints for biochemical states of nucleic acids. Here, we present a novel Quantum Molecular-Sequencing (QM-Seq) method which provides on fast nanoelectronic spectroscopy and unique electronic fingerprints of all DNA (A, G, T, C) and RNA nucleotides (A, G, C, U). We will show that QM-Seq spectra allows us to detect the biochemical state of all individual molecules, using facile identification of isomers and tautomer species in nucleic acids. We also demonstrate simultaneous identification of single nucleotide modifications (methylation here), which highlights the potential of QM-Seq as a versatile technique for epigenomics and personalized medicine.