Electrochemical plasmonic sensing system for highly selective multiplexed detection of biomolecules based on redox nanoswitches

In this paper, we present the development of a nanoswitch-based electrochemical surface plasmon resonance (eSPR) transducer for the multiplexed and selective detection of DNA and other biomolecules directly in complex media. To do so, we designed an experimental set-up for the synchronized measurements of electrochemical and electro-plasmonic responses to the activation of multiple electrochemically labeled structure-switching biosensors. As a proof of principle, we adapted this strategy for the detection of DNA sequences that are diagnostic of two pathogens (drug-resistant tuberculosis and Escherichia coli) by using methylene blue-labeled structure-switching DNA stem-loop. The experimental sensitivity of the switch-based eSPR sensor is estimated at 5 nM and target detection is achieved within minutes. Each sensor is reusable several times with a simple 8 M urea washing procedure. We then demonstrated the selectivity and multiplexed ability of these switch-based eSPR by simultaneously detecting two different DNA sequences. We discuss the advantages of the proposed eSPR approach for the development of highly selective sensor devices for the rapid and reliable detection of multiple molecular markers in complex samples.