Multiplexed single-molecule force spectroscopy using a centrifuge

Darren Yang, Andrew Ward, Ken Halvorsen () and Wesley P. Wong ()
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Darren Yang: School of engineering and applied sciences, Harvard University
Andrew Ward: Program in Cellular and Molecular Medicine, Boston Children’s Hospital
Ken Halvorsen: Program in Cellular and Molecular Medicine, Boston Children’s Hospital
Wesley P. Wong: Program in Cellular and Molecular Medicine, Boston Children’s Hospital

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: Abstract We present a miniature centrifuge force microscope (CFM) that repurposes a benchtop centrifuge for high-throughput single-molecule experiments with high-resolution particle tracking, a large force range, temperature control and simple push-button operation. Incorporating DNA nanoswitches to enable repeated interrogation by force of single molecular pairs, we demonstrate increased throughput, reliability and the ability to characterize population heterogeneity. We perform spatiotemporally multiplexed experiments to collect 1,863 bond rupture statistics from 538 traceable molecular pairs in a single experiment, and show that 2 populations of DNA zippers can be distinguished using per-molecule statistics to reduce noise.

Date: 2016
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DOI: 10.1038/ncomms11026

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