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Nanopore Sensing in Aqueous Two-Phase System: Simultaneous Enhancement of Signal and Translocation Time via Conformal Coating.

Nanofluidic resistive pulse sensing (RPS) has been extensively used to measure the size, concentration, and surface charge of nanoparticles in electrically conducting solutions. Although various methods have been explored for improving detection performances, intrinsic problems including the extremely low particle-to-pore volume ratio (<0.01%) and fast nanoparticle translocation (10-1000 µs) still induce difficulties in detection, such as low signal magnitudes and short translocation times. Herein, we present an aqueous two-phase system (ATPS) in a nanofluidic RPS for amplifying translocation signals and decreasing translocation speeds simultaneously. Two immiscible aqueous liquids build a liquid-liquid interface inside nanopores. As particles translocate from a high-affinity liquid phase into a lower-affinity one, the high-affinity liquid forms a conformal coating on the particles, which increases the effective particle size and amplifies the current-blockage signal. The translocation time is also increased, as the ATPS interface impedes the particle translocation. For 20 nm particles, 7.92-fold and 5.82-fold enhancements of signal magnitude and translocation time can be achieved. To our knowledge, this is the first attempt to improve nanofluidic RPS by treating an interface of solution reservoirs for manipulating target particles rather than nanopores. This direct particle manipulation allows us to solve the two intrinsic problems all at once.