On demand delivery and analysis of single molecules on a programmable nanopore-optofluidic device

M. Rahman, M. A. Stott, M. Harrington, Y. Li, M. J. N. Sampad, L. Lancaster, T. D. Yuzvinsky, H. F. Noller, A. R. Hawkins and H. Schmidt ()
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M. Rahman: University of California Santa Cruz
M. A. Stott: Brigham Young University
M. Harrington: University of California Santa Cruz
Y. Li: University of California Santa Cruz
M. J. N. Sampad: University of California Santa Cruz
L. Lancaster: University of California at Santa Cruz
T. D. Yuzvinsky: University of California Santa Cruz
H. F. Noller: University of California at Santa Cruz
A. R. Hawkins: Brigham Young University
H. Schmidt: University of California Santa Cruz

Nature Communications, 2019, vol. 10, issue 1, 1-7

Abstract: Abstract Nanopore-based single nanoparticle detection has recently emerged as a vibrant research field with numerous high-impact applications. Here, we introduce a programmable optofluidic chip for nanopore-based particle analysis: feedback-controlled selective delivery of a desired number of biomolecules and integration of optical detection techniques on nanopore-selected particles. We demonstrate the feedback-controlled introduction of individual biomolecules, including 70S ribosomes, DNAs and proteins into a fluidic channel where the voltage across the nanopore is turned off after a user-defined number of single molecular insertions. Delivery rates of hundreds/min with programmable off-times of the pore are demonstrated using individual 70S ribosomes. We then use real-time analysis of the translocation signal for selective voltage gating of specific particles from a mixture, enabling selection of DNAs from a DNA-ribosome mixture. Furthermore, we report optical detection of nanopore-selected DNA molecules. These capabilities point the way towards a powerful research tool for high-throughput single-molecule analysis on a chip.

Date: 2019
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DOI: 10.1038/s41467-019-11723-7

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