Electrochemical sensing in complex matrices

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Achieving specific measurements of libraries of molecules directly in complex matrices, like undiluted whole blood, remains an important socioeconomical challenge. This is because common detection strategies rely on multi-step and complex processes that ultimately lead to cumbersome and laboratory-bound approaches that require hours/days to return a single answer. Mother nature, in contrast, is able to efficiently detect molecules with exquisite specificities to produce strong biochemical responses in spite of the complex nature of the matrix in which it operates. She does so in part thanks to conformational selection, a detection scheme that revolves around the change in shape of a biomolecular receptor upon recognition of a target molecule. Inspired by this unprecedented capability and with a unique expertise in analytical electrochemistry, my research program aims to understand the mechanisms that limits our ability to artificially detect molecules directly in undiluted complex matrices. Specifically, we are interested in understanding the governing physicochemical properties of electrode-attached biomolecular receptors that influence their ability to recognize molecules and undergo binding-induced conformational change in these matrices. We plan to study these systems by developing original electrochemical biophysical approaches to help us guide the design of innovative generalizable, single-step and reagentless electroanalytical sensing platforms able to continuously monitor molecules. We are notably interested in developing sensing approaches for molecules that remain challenging to measure with sufficient temporal resolution due to their fast metabolism (i.e., neurotransmitters). In response, to achieve highly-time resolved measurements of such class of molecules, we plan to develop electrochemical interrogation strategies to afford highly-time resolved measurements, notably through the inception of electrochemical phase interrogation, a technique that achieves millisecond-resolved measurements. Neurotransmitters are also challenging to measure with sufficient specificity in complex matrices which we plan to address by developing new classes of electrochemically-triggered switch-based sensors that rely on the introduction of non-nucleic acid macromolecular receptors. We consider that reaching these milestones is essential to increase the specificity and sensitivity with which we can perform molecular measurements directly in undiluted complex matrices. We envision that these new classes of sensors will likely have an impact to address the socioeconomical need in developing unique, convenient and rapid personalized medicine approaches for unprecedented real-time detection of molecules as opposed to systematically resorting to cumbersome, slow laboratory-bound processes ran by trained personnel