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 108–1010 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 103 reduction in the limit of detection compared with existing methods, while still maintaining efficient throughput.
Highlights
Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data
Nanopore sensing has several drawbacks with one of the most problematic being the lack of efficiency when trying to detect individual molecules from the bulk solution. This problem extends further and is fundamental to many surfacebased biosensors[8]. This stems from the fact that the dominant mechanism of capture and detection is diffusion-limited resulting in only a small fraction of the total sample volume being accessed
The DEP trap provides on-demand control of the capture volume but can significantly increase the number of molecules being detected per unit time even at concentrations of a few femtomolar
Summary
Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data. Both studies made use of the electrophoretic properties of DNA to enhance the capture rate, while others have attempted to use pressure gradients to add a level of control to the translocation process[16] All these methods have limited ability to concentrate and perform high-throughput detection of ultra-dilute samples. These studies have focused on DNA, it should be noted that the goal to increase capture rate has far-reaching applications related to rare event detection and is not exclusively directed towards DNA sequencing; especially if DNA translocations are successfully slowed down such that the inter-event time is not a limiting factor. The reported technique pushes the envelope of high-sensitivity and amplification-free single-molecule detection and paves the way for high-speed and high-throughput detection of ultra-dilute samples and rare events
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