High bandwidth approaches in nanopore and ion channel recordings - A tutorial review

Abstract

Transport processes through ion-channel proteins, protein pores, or solid-state nanopores are traditionally recorded with commercial patch-clamp amplifiers. The bandwidth of these systems is typically limited to 10 kHz by signal-to-noise-ratio (SNR) considerations associated with these measurement platforms. At high bandwidth, the input-referred current noise in these systems dominates, determined by the input-referred voltage noise of the transimpedance amplifier applied across the capacitance at the input of the amplifier. This capacitance arises from several sources: the parasitic capacitance of the amplifier itself; the capacitance of the lipid bilayer harboring the ion channel protein (or the membrane used to form the solid-state nanopore); and the capacitance from the interconnections between the electronics and the membrane. Here, we review state-ofthe-art applications of high-bandwidth conductance recordings of both ion channels and solid-state nanopores. These approaches involve tightly integrating measurement electronics fabricated in complementary metal-oxide semiconductors (CMOS) technology with lipid bilayer or solid-state membranes. SNR improvements associated with this tight integration push the limits of measurement bandwidths, in some cases in excess of 10 MHz. Recent case 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 insights into structure-function relations of these ion-channel proteins as the temporal resolutions of functional recordings matches time scales achievable with state-of-the-art molecular dynamics simulations.

A Functional K+ Channel from Tetraselmis Virus 1, a Member of the Mimiviridae

“…It is also possible that they are not properly folded and/or inserted into the membrane in the in vitro translation system with the result that they are not functional in the host bilayer. Another reasonable explanation for the negative results is that the channels may have a very small unitary conductance and/or very high flicker type open probability, which is not resolved with the standard measuring equipment [ 48 , 49 ].…”

The OpenPicoAmp-100K, an Open-source High Performance Amplifier for Single Channel Recording in Planar Lipid Bilayers

“…7 are the fastest recordings ever reported using classical bilayer membrane and discrete component amplifier as opposed to the complicated microbilayer membrane fabrication and customized integrated circuit amplifiers [2,10,15 and Supplementary Information]. Further reading on the suggestions and practical experimental approaches for noise optimization in high bandwidth ion channel recordings can be found in the literature [10,13,17,19,25,26]. At last, special post-recording denoising and current idealization techniques also deserve attention when working with high bandwidth ion channel data.…”

The OpenPicoAmp-100k : an open-source high performance amplifier for single channel recording in planar lipid bilayers

“…To the best of our knowledge, the results shown for alamethicin channel in Figure 7 are the fastest recordings ever reported using classical bilayer membrane and discrete component amplifier as opposed to the complicated microbilayer membrane fabrication and customized integrated circuit amplifiers [2,10,15 and Supplementary Information]. Further reading on the suggestions and practical experimental approaches for noise optimization in high bandwidth ion channel recordings can be found in the literature [10,13,17,19,25,26]. At last, special post-recording denoising and current idealization techniques also deserve attention when working with high bandwidth ion channel data.…”