Orthogonally tunable solid-state nanopore modifications for improved biosensing

Advances in biosensor sensitivity, specificity, and accessibility are required for the development of next generation diagnostic tools. Solid-state nanopores consisting of sub-10 nm in diameter pores drilled into an insulating material show promise as single-molecule biosensors for detecting both nucleic acid and protein targets. However, this technology is limited by rapid analyte translocation speeds and complex and/or inconsistent device assemblies. To address these limitations, we have developed two orthogonally tunable solid-state nanopore modifications which slow nucleic acid translocation speeds and streamline device assembly and manipulation through the use of a 3-dimensional polymeric nanofiber mesh (NFM) coating and the development of a novel microfluidic device, respectively. A range of translocation speeds from 1x to >100x slower than a bare nanopore were achieved by tuning the chemical composition of the NFM coating. In addition, a microfluidic device was designed to streamline nanopore assembly enabling facile integration of both sample purification protocols and single-molecule detection using optical and electronic readouts simultaneously.