Fast capture and multiplexed detection of short multi-arm DNA stars in solid-state nanopores. Issue 35 (6th August 2019)

• Record Type: Journal Article
• Authors: He, Liqun; Karau, Philipp; Tabard-Cossa, Vincent
• Is Part Of: Nanoscale. Volume 11:Issue 35(2019)
• Page Start: 16342
• Page End: 16350
• Publication Date: 2019-08-06
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/c9nr04566j
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : The capture and translocation characteristics of multi-arm DNA star nanostructures are studied to evaluate their potential as advanced labels for improved solid-state nanopore sensing performance. Abstract : Fast and multiplexed detection of low-abundance disease biomarkers at the point-of-need would transform medicine. Nanopores have gained attention as single-molecule counters to electrically detect a range of biological molecules in a handheld format, but challenges remain before diagnostic applications can emerge. For solid-state nanopore sensors, the specificity of the ionic current signatures and the rate of target capture required to simultaneously recognize and rapidly count a mixture of molecular targets in a complex sample are active areas of research. Herein, we study the capture and translocation characteristics of short N -arm star shaped DNA nanostructures to evaluate their potential as a family of surrogate label molecules for biomarkers of interest, designed for fast and reliable multiplexed detection based on conductance blockages. Simple hybridization of a varying number of short, easily synthesized 50 bp ssDNA strands allows the number of arms in the star shape DNA to be controlled from N = 3 to 12. By introducing more arms to the nanostructures, we show that we can controllably increase the nanopore signal-to-noise ratio for a range of pore sizes, producing conductance blockages which increase linearly with the number of arms, and we demonstrate conductance-based multiplexing through simultaneous detection of three such nanostructures. Moreover, the increased molecular signal strength facilitates detection under salt concentration asymmetries, allowing for a capture rate enhancement of two orders of magnitude without compromising the nanopore temporal and ionic signals. Together, these attributes (strong signal, multiplexing potential and increased counting rate) make the N -arm star DNA-based nanostructures promising candidates as proxy labels for the detection of multiple biomarkers of interest in future high sensitivity single-molecule solid-state nanopore-based assays.