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Direct Electrical Detection of sub-aM DNA Concentrations

By Maoxiang Guo, Narayanan Madaboosi, Felix Neumann, Mats Nilsson, Wouter van der Wijngaart

Posted 04 Apr 2020
bioRxiv DOI: 10.1101/2020.04.03.023176

Sensors for detecting ultra-low concentrations are limited by the efficient transport of target molecules from large sample volumes to small detection regions. We here report a small-format digital DNA sensor in the shape of a microporous membrane that electrically detects DNA substrates with a concentration as low as 790 zM. This ultra-high sensitivity follows from optimising the mass transport of target DNA to specific receptors on the membrane across multiple spatial scales. mm-sized membranes support the rapid convection of a large sample volume to the detection zone; micrometer-sized pores ensure that DNA diffusion to the surface-based receptors dominates over convective loss through the pores (low Peclet number), and; at the nm-scale, target-receptor binding dominates over diffusive transport (high Damkoehler number). After their efficient capture, the DNA molecules are converted with high specificity into trans-membrane gold nanowires that are detected using a simple, high signal-to-noise, electrical resistance measurement. This sensor design is of interest for detecting low-abundant target molecules without the need for sample amplification or up-concentration, and the mass-transport strategy could be adapted to other surface-based sensing schemes.

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