Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data. One exceptionally promising route is in the use of nanopore sensors. However, a well-known complexity is that detection and capture is predominantly diffusion limited. This problem is compounded when taking into account the capture volume of a nanopore, typically 10 8-10 10 times smaller than the sample volume. To rectify this disproportionate ratio, we demonstrate a simple, yet powerful, method based on coupling single-molecule dielectrophoretic trapping to nanopore sensing. We show that DNA can be captured from a controllable, but typically much larger, volume and concentrated at the tip of a metallic nanopore. This enables the detection of single molecules at concentrations as low as 5 fM, which is approximately a 10 3 reduction in the limit of detection compared with existing methods, while still maintaining efficient throughput.
Bibliographical noteFunding Information:
K.J.F. acknowledges support of the Whitaker International Program by the IIE. J.B.E. acknowledges BBSRC and the receipt of an ERC starting investigator grant. L.M.O., A.B. and S.-H.O. acknowledge support from the U.S. National Science Foundation (NSF CAREER Award) and the MnDRIVE Initiative from the State of Minnesota. L.M.O. acknowledges support from the National Institutes of Health biotechnology training grant (T32 GM008347) and the NSF Graduate Research Fellowship Program. Computational modelling using COMSOL Multiphysics 4.3a was performed through the University of Minnesota Supercomputing Institute. Finally, we thank Ulrich Keyser for useful discussions.