Abstract

Nanopore based sensors promise ultrasensitive detection of an array of nucleic acid, peptide, and protein biomarkers. However, the low physiological concentrations of cancer biomarkers can greatly limit their detection in conventional nanopore sensors due to the low trapping rate of these markers inside of the nanopore. A previous study used a salt gradient to generate an enhanced electric field (EEF) in a synthetic nanopore, which increased the capture rate of double-stranded DNA. In this study, we have demonstrated that the use of an EFF in a biological pore can lead to dramatic increases in the trapping frequency of single stranded DNA (∼80x), double stranded DNA (∼30x), peptides (∼15x) and DNA-protein complex (∼30x). We then provide evidence that this increase of trapping frequency is directionally and molecularly-dependent. Finally, picogram level of liver-specific microRNA was successfully detected in the pore using this salt gradient.

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