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.