Nanopore sensing at ultra-low concentrations using single-molecule dielectrophoretic trapping

TLDR

Single‑molecule techniques promise to revolutionize healthcare by generating vast genetic and proteomic data, and nanopore sensors are a promising route, but detection is largely diffusion‑limited and the nanopore capture volume is 10^8–10^10 times smaller than the sample volume. The authors address this imbalance by coupling single‑molecule dielectrophoretic trapping to nanopore sensing, a simple yet powerful method. The method captures DNA from a larger volume and concentrates it at the nanopore tip, enabling single‑molecule detection at 5 fM—about a 10^3‑fold lower limit of detection than existing methods—while preserving efficient throughput.

Abstract

Abstract 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.