A nanopore interface for higher bandwidth DNA computing

Karen Zhang, Yuan-Jyue Chen, Delaney Wilde, Kathryn Doroschak, Karin Strauss, Luis Ceze, Georg Seelig and Jeff Nivala ()
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Karen Zhang: University of Washington
Yuan-Jyue Chen: Microsoft Research
Delaney Wilde: University of Washington
Kathryn Doroschak: University of Washington
Karin Strauss: Microsoft Research
Luis Ceze: University of Washington
Georg Seelig: University of Washington
Jeff Nivala: University of Washington

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract DNA has emerged as a powerful substrate for programming information processing machines at the nanoscale. Among the DNA computing primitives used today, DNA strand displacement (DSD) is arguably the most popular, with DSD-based circuit applications ranging from disease diagnostics to molecular artificial neural networks. The outputs of DSD circuits are generally read using fluorescence spectroscopy. However, due to the spectral overlap of typical small-molecule fluorescent reporters, the number of unique outputs that can be detected in parallel is limited, requiring complex optical setups or spatial isolation of reactions to make output bandwidths scalable. Here, we present a multiplexable sequencing-free readout method that enables real-time, kinetic measurement of DSD circuit activity through highly parallel, direct detection of barcoded output strands using nanopore sensor array technology (Oxford Nanopore Technologies’ MinION device). These results increase DSD output bandwidth by an order of magnitude over what is currently feasible with fluorescence spectroscopy.

Date: 2022
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DOI: 10.1038/s41467-022-32526-3

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