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

渴望：汗水、感觉和信号（S3）？

• 批准号: 1347725
• 负责人: Jason Heikenfeld
• 金额: $ 16万
• 依托单位: University of Cincinnati Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1347725&HistoricalAwards=false
• 关键词: EAGER; Sweat; Sense; Signal; S3

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.

目的与血液、尿液、呼吸和唾液相比，用于医学诊断的汗液在很大程度上被忽视了。 现在的研究表明，可以在汗液中发现许多用于健康监测或诊断的水溶性生物标志物，其浓度与血液中的浓度相当。因此，医学科学可能正处于非侵入性生理传感基本方法变革的边缘。 尤其具有影响力的是可快速读取浓度的可穿戴生物标记传感器。 然而，这将需要新的电传感技术，因为当前的汗液生物标志物生物传感只能进行无机离子传感（水合、婴儿囊性纤维化）。 迈向汗液分子生物传感需要检测 1-10 pM 范围内的生物标志物浓度。 对生物流体中电传感的初步研究表明，传感低至 pM 水平是可能的。 然而，无论是在实际复杂汗液样本基质中的传感还是亚皮米传感都尚未得到证实。 展示汗液中生物标记物的亚皮姆电传感将为可穿戴汗液生物传感产品的可行性提供突破性证据。 智力价值该 EAGER 提案的总体目标是展示亚皮姆电阻抗光谱检测，在真实的汗液中，至少 3 个具有重要医学诊断意义的生物标志物。 选择阻抗谱是因为它对固定在传感电极表面上的各种生物识别元件高度可调，并且当生物识别元件捕获生物标记物时，它提供多方面的检测，包括电阻、电容、电荷转移和电压响应形状变化。 拟议的生物标志物重点关注汗液中至少 1-10 pM 浓度范围内存在的生物标志物：(1) 促炎和抗炎细胞因子； (2)神经递质。 实现亚皮米级灵敏度的具体目标包括：（1）叉指电极与生物标记/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且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与波形形状、电位大小、电解质溶液 pH 值和离子强度等更精细刺激的关系。 这些目标的成功将激发人们对汗液生物传感的兴趣激增，并促使人们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医疗和预防性护理来降低总医疗保健成本。 广泛的社会影响包括运动员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先进治疗诊断学的健康基线。 传播计划包括组织一个自我维持的年度国际研讨会，主题是汗液中生物标志物的传感。 该 EAGER 将加强汗液传感研究和教育基础设施。 综合教育计划包括对大学本科生研究合作社的支持，该合作社随后将在 PI 的合作伙伴联邦实验室实习。