Single-molecule confinement with uniform electrodynamic nanofluidics. Issue 17 (6th August 2020)

• Record Type: Journal Article
• Authors: Ghosh, Siddharth; Karedla, Narain; Gregor, Ingo
• Is Part Of: Lab on a chip. Volume 20:Issue 17(2020)
• Page Start: 3249
• Page End: 3257
• Publication Date: 2020-08-06
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/d0lc00398k
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : A single-molecule nanofluidic detection method resolving fundamental limit of molecular shot noise along with 1D manipulation of sub-3 nm sized single molecules – a potential application for early detection of COVID-19, cancer and protein misfolding. Abstract : To date, we could not engineer Nature's ability to dynamically handle diffusing single molecules in the liquid-phase as it takes place in pore-forming proteins and tunnelling nanotubes. Consistent handling of individual single molecules in a liquid is of paramount importance to fundamental molecular studies and technological benefits, like single-molecule level separation and sorting for early biomedical diagnostics, microscopic studies of molecular interactions and electron/optical microscopy of molecules and nanomaterials. We can consistently resolve the dynamics of diffusing single molecules if they are confined within a uniform dielectric environment at nanometre length-scales. A uniform dielectric environment is the key characteristic since intrinsic electronic properties of molecules were modified while interacting with any surfaces, and the effect is not the same from one dielectric surface to another. We present dynamic nanofluidic detection of optically active single molecules in a liquid. An all-silica nanofluidic environment was used to electrokinetically handle individual single-molecules where molecular shot noise was resolved. We recorded the single-molecule motion of small fragments of DNA, carbon-nanodots, and organic fluorophores in water. The electrokinetic 1D molecular mass transport under two-focus fluorescence correlation spectroscopy (2fFCS) showed confinement-induced modified molecular interactions (due to various inter-molecular repulsive and attractive forces), which have been theoretically interpreted as molecular shot noise. Our demonstration of high-throughput nanochannel fabrication, 2fFCS-based 1D confined detection of fast-moving single molecules and fundamental understanding of molecular shot noise may open an avenue for single-molecule experiments where physical manipulation of dynamics is necessary.