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A nanopore interface for higher bandwidth DNA computing

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. Toe-hold-mediated strand displacement (DSD) is a widely used molecular tool in applications such as DNA computing and nucleic acid diagnostics. Here the authors characterize dozens of orthogonal barcode sequences that can be used for monitoring the output kinetics of multiplexed DSD reactions in real-time using a commercially-available portable nanopore array device.

SUBMITTER: Zhang K

PROVIDER: S-EPMC9392746 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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