Comparing current noise in biological and solid-state nanopores

Abstract

Nanopores bear great potential as single-molecule tools for bioanalytical sensing and sequencing, due to their exceptional sensing capabilities, high-throughput, and low cost. The detection principle relies on detecting small differences in the ionic current as biomolecules traverse the nanopore. A major bottleneck for the further progress of this technology is the noise that is present in the ionic current recordings, because it limits the signal-to-noise ratio and thereby the effective time resolution of the experiment. Here, we review the main types of noise at low and high frequencies and discuss the underlying physics. Moreover, we compare biological and solid-state nanopores in terms of the signal-to-noise ratio (SNR), the important figure of merit, by measuring free translocations of a short ssDNA through a selected set of nanopores under typical experimental conditions. We find that SiNx solid-state nanopores provide the highest SNR, due to the large currents at which they can be operated and the relatively low noise at high frequencies. However, the real game-changer for many applications is a controlled slowdown of the translocation speed, which for MspA was shown to increase the SNR >160-fold. Finally, we discuss practical approaches for lowering the noise for optimal experimental performance and further development of the nanopore technology.

Single-molecule conformational dynamics of viroporin ion channels regulated by lipid-protein interactions

“…Here, we use the analysis of fluctuations to identify the mechanisms of CSFV p7 pore formation and to validate the existence of different pore conformations. Detecting the sources of noise in both synthetic and biological nanopores is not only important for academic purposes, but also helps to reduce the signal-to-noise ratio determining the time resolution of experimental set-ups in bioanalytical [38] and large-scale technological applications [39] . To complement noise analysis, we analyze the effect of p7 on ER-like membranes considering the effect of solution acidity, using AFM, which provides nanometer resolution.…”

Sensing with Nanopores and Aptamers: A Way Forward

“…Biological nanopores have the advantages to offer highly reproducible translocation results thanks to a well-defined pore structure. The lipid bilayer in which they are embedded offers low electrical noise [ 23 , 25 ]. Their chemical structure can be tuned with the addition of functional groups thanks to genetic or molecular engineering [ 19 ] and the variety of available biological pores increases over time [ 42 ].…”

“…Several reviews have focused on nanopores and their single molecule detection principle and applications [ 5 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. As mentioned previously, in most cases, the use of functional molecules brings new capabilities in term of detection, recognition, selectivity and even function to the nanopores.…”

Label-free amino acid identification forde novoprotein sequencing via tRNA charging and current blockade in a nanopore

“…Define the signal-to-noise ratio (SNR) as SNR = IAN / IRMS (14) A sufficiently high SNR can ensure that the blockade current due to G can always be distinguished from IRMS. In [28] the SNR for different kinds of pores, biological and synthetic, is given. It ranges from 4 to nearly 40, which is adequate for the present purpose.…”

“…It ranges from 4 to nearly 40, which is adequate for the present purpose. Various methods of increasing the SNR for both kinds of pores are discussed in [28]. In particular slowing down the analyte as it translocates through the pore can lead to a significant increase in SNR by reducing the bandwidth required for detection, and at the same time decreases high frequency noise.…”