Block Optical DNA Sequencing with Plasmonic Substrates for Rapid Biomarker Diagnostics

Precision medicine requires high-throughput point-of-care diagnostics with multiomics capability for sensing biomolecules and their molecular variants. In a push for improved precision diagnostics, we describe an optical sequencing platform that uses surface-enhanced Raman spectroscopy (SERS) measurements from plasmonic nanostructured surfaces and nanoparticles for label-free determination of nucleobase content in DNA k-mer blocks. With SERS on cationic silver nanoparticles, we achieved >93% accuracy for predicting A-G-C-T content in 10-mer DNA blocks. The high-accuracy measurements were used with a content-scoring bioinformatics algorithm to correctly identify a β-lactamase antibiotic resistance gene and confirm the Pseudomonas aeruginosa pathogen from merely <12 measurements (<15% coverage of the gene) [1,2]. We further proved applicability on RNA and chemically modified nucleobases for extensions to transcriptomics and epigenomics. With the versatility of plasmonic substrates for simple data acquisition, resolution to single-molecules, and multiplexing, optical sequencing can provide rapid biomarker diagnostics in the clinical setting [3].

[1] Korshoj, Nagpal, ACS Appl. Mater. Interfaces 2019; [2] Korshoj, Nagpal, Comput. Biol. Med. 2019; [3] Sagar, Korshoj, et al. Small 2018