Cooperative electrolyte-PEG interactions drive the signal amplification in a solid-state nanopore

Nanopore systems have emerged as a leading platform for the analysis of biomolecular complexes with single molecule resolution. However, the analysis of several analytes like short nucleic acids or proteins with nanopores represents a sensitivity challenge, because their translocation lead to small signals difficult to distinguish from the noise. Here, we report a simple method to enhance the signal to noise ratio in nanopore experiments by a simple modification of the solution used in nanopore sensing. The addition of poly-ethylene glycol (PEG) and the careful selection of the supporting electrolyte leads to large signal enhancement. We observed that the translocation dynamics are in good agreement with an established method that uses the lattice energy of an electrolyte to approximate the affinity of an ion to PEG. We identified CsBr as the optimal supporting electrolyte to complement PEG to enable the analysis of dsDNA at 500 kHz bandwidth, and the detection of dsDNA as short as 75 bp. ### Competing Interest Statement The authors have declared no competing interest. * ABBREVIATIONS : PBS : Phosphate Buffered Saline PEG : Poly(ethylene) glycol dsDNA : double stranded DNA SNR : signal-to-noise ratio MW : molecular weight