Andreas J.W. Hartel, siddharth Shekar, Peijie Ong, Indra Schroeder, Gerhard Thiel, Kenneth L. Shepard. High bandwidth approaches in nanopore and ion channel recordings – A tutorial review. Analytica Chimica Acta. January 5, 2019, DOI: 10.1016/j.aca.201901.034

Transport processes through ion-channel proteins, protein pores, or solid-state nanopores are tradi-tionally recorded with commercial patch-clamp amplifiers. The bandwidth of these systems is typicallylimited to 10 kHz by signal-to-noise-ratio (SNR) considerations associated with these measurementplatforms. At high bandwidth, the input-referred current noise in these systems dominates, determinedby the input-referred voltage noise of the transimpedance amplifier applied across the capacitance at theinput of the amplifier. This capacitance arises from several sources: the parasitic capacitance of theamplifier itself; the capacitance of the lipid bilayer harboring the ion channel protein (or the membraneused to form the solid-state nanopore); and the capacitance from the interconnections between theelectronics and the membrane. Here, we review state-of-the-art applications of high-bandwidthconductance recordings of both ion channels and solid-state nanopores. These approaches involvetightly integrating measurement electronics fabricated in complementary metal-oxide semiconductors(CMOS) technology with lipid bilayer or solid-state membranes. SNR improvements associated with thistight integration push the limits of measurement bandwidths, in some cases in excess of 10 MHz. Recentcase studies demonstrate the utility of these approaches for DNA sequencing and ion-channel recordings.In the latter case, studies with extended bandwidth have shown the potential for providing new insightsinto structure-function relations of these ion-channel proteins as the temporal resolutions of functionalrecordings matches time scales achievable with state-of-the-art molecular dynamics simulations.