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

目的与血液、尿液、呼吸和唾液相比，汗液用于医学诊断在很大程度上被忽视了。研究表明，许多用于健康监测或诊断的水溶性生物标志物可以在汗液中找到，其浓度与血液中的浓度相当。因此，医学可能正处于非侵入性生理传感基本方法的变革性转变的边缘。特别有影响的将是提供快速浓度读数的可穿戴生物标记传感器(S)。然而，这将需要新的电子传感技术，因为目前的汗液生物标志物生物传感只能检测无机离子(水合作用、婴儿囊性纤维化)。在汗液中进行分子生物传感需要在下午1-10点的范围内检测生物标记物的浓度。对生物体液中电学传感的初步研究表明，传感到PM水平是可能的。然而，既没有在实际复杂的汗液样本矩阵中进行传感，也没有进行亚PM传感。展示汗液中生物标志物的亚PM电感测将为可穿戴汗液生物传感产品的可行性提供突破性证据。智慧价值这项急切的提案的总体目标是展示在真实汗液中至少检测到3种重要医学诊断的生物标志物的亚PM电阻抗谱检测。选择阻抗谱是因为它对固定在传感电极表面的各种生物识别元件具有高度的可调性，并且它提供了多方面的检测，包括生物识别元件捕获生物标志物时的电阻、电容、电荷转移和电压响应形状变化。建议的生物标志物将集中在汗液中存在的那些至少在1-10 PM浓度范围内的物质：(1)促炎和抗炎细胞因子；以及(2)神经递质。导致亚PM灵敏度的具体目标包括：(1)交叉电极与生物标志物/生物识别元件响应的频率匹配；(2)发现生物识别元件的最佳和高度均匀的表面取向以获得最大阻抗响应；(3)深入研究电荷转移、形状变化、离子屏蔽和其他因素随更精细刺激的函数，如波形形状、电势大小、电解液pH和离子强度。这些目标的成功将激发人们对汗液生物传感的兴趣激增，并使人们能够追求广泛的商业产品。更广泛的影响：预计拟议工作的成功将通过推进个性化药物和预防性护理来降低总卫生保健成本。广泛的社会影响包括田径和消防员的热应激管理，提高飞行员和卡车司机的警觉性，士兵创伤后应激障碍的预防，以及高级心理治疗的健康基线。传播计划包括组织一次自给自足的国际汗液生物标记物感测国际讲习班。这一渴望将加强汗液感应研究和教育的基础设施。综合教育计划包括支持该大学的一个本科生研究合作社，然后该合作社将在Pi的合作伙伴联邦实验室实习。

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.