Signal amplification in electrochemical DNA biosensors using target-capturing DNA origami tiles

Williamson, Paul and Piskunen, Petteri and Ijäs, Heini and Butterworth, Adrian and Linko, Veikko and Corrigan, Damion K. (2023) Signal amplification in electrochemical DNA biosensors using target-capturing DNA origami tiles. ACS Sensors, 8 (4). pp. 1471-1480. ISSN 2379-3694 (https://doi.org/10.1021/acssensors.2c02469)

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Abstract

Electrochemical DNA (e-DNA) biosensors are feasible tools for disease monitoring, with their ability to translate hybridization events between a desired nucleic acid target and a functionalized transducer, into recordable electrical signals. Such an approach provides a powerful method of sample analysis, with a strong potential to generate a rapid time to result in response to low analyte concentrations. Here we report a strategy for the amplification of electrochemical signals associated with DNA hybridization, by harnessing the programmability of the DNA origami method to construct a sandwich assay to boost charge transfer resistance (RCT) associated with target detection. This allowed for an improvement in sensor limit of detection by two-orders of magnitude compared to a conventional label-free e-DNA biosensor design and linearity for target concentrations between 10 pM – 1 nM without the requirement for probe labeling, or enzymatic support. Additionally, this sensor design proved capable of achieving a high degree of strand selectivity in a challenging DNA-rich environment. This approach serves as a practical method for addressing strict sensitivity requirements necessary for a low cost point-of-care (PoC) device.

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