Osmosis-Driven Motion-Type Modulation of Biological Nanopores for Parallel Optical Nucleic Acid Sensing

Recent
developments in nanopore sequencing have inspired new concepts in
precision medicine but limited in throughput. By optically encoding
calcium flux from an array of nanopores, parallel measurements from
hundreds of nanopores were reported, while lateral drifts of biological
nanopores set obstacles for signal processing. In this paper, optical
single-channel recording (oSCR) serves to track nanopores with high
precision and a general principle of nanopore motion kinetics is quantitatively
investigated. By finely adjusting the osmosis-oriented interactions
between the lipid/substrate interfaces, motions of nanopores could
be controllably restricted. Improved signal-to-noise ratio is observed
from motion-restricted nanopores, which is experimentally demonstrated.
To systematically evaluate oSCR with asymmetric salt concentrations,
a finite element method simulation is established. oSCR with an array
of immobilized nanopores suggests new strategies for sequencing DNA
by microscopic imaging in high throughput and is widely applicable
to the investigation of other transmembrane proteins.