The Emergence of Nanofluidics for Single-Biomolecule Manipulation and Sensing.

Driven by recent advancements in nanofabrication techniques, single-molecule sensing and manipulations in nanofluidic devices are rapidly evolving. These sophisticated biosensors have already had significant impacts on basic research as well as on applications in molecular diagnostics. The nanoscale dimensions of these devices introduce new physical phenomena by confining the biomolecules in at least one dimension, creating effects such as biopolymer linearization, stretching, and separation by mass that are utilized to enhance the biomolecule sensing resolutions. At the same time, the suppressed diffusional motion allows for better single-molecule SNR (signal-to-noise ratio) sensing over time. In particular, nanofluidic devices based on nanochannels have been established as promising technologies for the linearization of ultralong genomic DNA molecules and for optical genome mapping, opening a window to directly observe and infer genome organization. More recently, nanochannels have shown promising capabilities for single-molecule protein sizing, separation, and identification. Consequently, this technology is attracting remarkable interest for applications in single-molecule proteomics. In this review, we discuss the recent advancements of nanochannel-based technologies, focusing on their applications for single-molecule sensing and the characterization of a wide range of biomolecules.