EAGER: Sweat, Sense, and Signal (S3) ? Demonstration of fM to pM Electrical Sensing of BioMarkers in Sweat

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ObjectiveSweat for medical diagnostics has been largely overlooked in comparison to blood, urine, breath, and saliva. Research now reveals that numerous water-soluble biomarkers for health monitoring or diagnosis can be found in sweat at comparable concentrations as in blood. Therefore, medical science is potentially on the verge of a transformative shift in fundamental approaches for non-invasive physiological sensing. Of particular impact would be wearable biomarker sensors providing a fast readout of concentration(s). However, this will require new electrical sensing technology, as current sweat biomarker biosensing is capable of only inorganic ion sensing (hydration, infant cystic fibrosis). Moving toward molecular biosensing in sweat will require sensing of biomarker concentrations in the 1-10 pM range. Preliminary studies of electrical sensing in biofluids suggest that sensing down to pM levels is possible. However, neither sensing in the actual complex sweat sample matrix nor sub-pM sensing have been demonstrated. Demonstrating sub-pM electrical sensing of biomarkers in sweat would provide breakthrough evidence on the viability of wearable sweat bio-sensing products.Intellectual meritThe overall objective for this EAGER proposal is to demonstrate sub-pM electrical impedance spectroscopy detection, in real sweat, of at least 3 biomarkers of significant medical diagnostics. Impedance spectroscopy is chosen because it is highly tunable to the various biorecognition elements that are immobilized on the sensing electrode surface, and it provides multifaceted detection including resistance, capacitance, charge transfer, and voltage responsive shape-change as biomarkers are captured by the biorecognition elements. The proposed biomarker focus will be on those which exist in sweat in at least the 1-10 pM concentration range: (1) pro-inflammatory and anti-inflammatory cytokines; and (2) neurotransmitters. Specific aims leading to sub-pM sensitivity include: (1) frequency matching of interdigitated electrodes to the biomarker / biorecognition element response; (2) discovery of the optimal and highly homogeneous surface-orientation of the biorecognition elements for maximum impedance response; (3) deep investigation of charge-transfer, shape-change, ion-screening, and other factors as a function of finer stimuli such as waveform shape, potential magnitude, electrolyte solution pH, and ionic strength. Success with these aims will then stimulate a surge of interest in sweat biosensing and enable pursuit of a broad array of commercial products. Broader Impacts:It is expected that the Success of the proposed work will lead to lower total health care costs by advancing personalized medicine and preventative care. Broad social impacts include heat-stress management in athletics and firefighters, augmenting alertness in pilots and truckers, soldier PTSD prevention, and health baselining for advanced theranostics. Dissemination plan includes organizing a self-sustaining annual international workshop on the Sensing of Biomarkers in Sweat. This EAGER will enhance infrastructure in research and education for sweat sensing. Integrated education plan includes support of an undergraduate research co-op at the university, who will then later intern at PI's partner federal labs.