Authors:

Ethan Brazelton

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About Paper:

Electrochemical sensors offer a novel instrument for continuous monitoring of biomarkers with physiological precision, while offering alternatives to invasive lab testing in clinical environments. Circadian rhythms (CR) are innate 24-hour cycles that regulate the timing of biological systems to coordinate daily rhythms of sleep/waking hours, body temperature, and secretion of various hormones, such as melatonin and cortisol. Our aim is to develop a noninvasive, wearable sensing platform for continuous monitoring of relevant biomarkers in interstitial fluid (ISF) to facilitate control over biological clocks through pharmacological interventions. Physiological monitoring (i.e., vitals, heart rate) is a key part of this endeavor; however, biochemical monitoring would enable high-precision monitoring for the monitoring of pharmacological treatments, particularly for sleep dysregulation such as insomnia or sleep apnea. The nanomolecular pendulum (NMP) enables a reagentless sensing approach for molecular analytes to be analyzed in situ absent external sample preparation. This technology utilizes field-induced diffusion of analytes and electrochemical reporters to the electrode surface to recognize sensitive, time-resolved changes in electrical current to monitor bound and unbound states. Small molecule analytes such as melatonin and cortisol necessitate smaller analyte receptors to enable precision measurements. Traditional modalities such as antibodies are prohibitively large, so structure-switching aptamers, which undergo measurable conformation changes upon target binding, are used to produce changes in hydrodynamic radii (as measured by dynamic light scattering methods). Chronoamperometry allows for the detection of melatonin concentration-dependent current increases, validated in 1x PBS buffer, simulated human ISF, and 10% whole blood. The success of this project offers potential for the further development of a living pharmacy, which can deliver CR-regulating therapies in response to real-time dysregulation. Furthermore, the success of switching aptamers for small-molecule detection will allow the NMP to be employed for diverse small-molecule sensing needs in a variety of biosensing contexts for medical applications. OOOOH O HOSE HHO HOOSCOSOH OST SCO OHCOOSOHOOCHDOOCOOHOHOCO OCHO ©FFDHOHDIDIIDIDHHFDOHIDIDHDDOHHHIDDIHHHIDIDVIIIOI

Source:

Northwestern University

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Co-authors:

Ethan Brazelton