Chronologically Correlated Sweat Biosensing

在具有巨大上升潜力的非侵入性可穿戴技术中，汗液传感技术可以说是最不发达的。尽管如此，随着许多汗液电解质、代谢物、氨基酸、蛋白质和其他生物标记物在监测精神和身体状况以及/或疾病方面显示出希望，人们的兴奋情绪正在积聚。然而，不幸的是，许多可以用于汗液的商用技术解决方案需要大约10微升的S样本量，对于连续的汗液分析来说，这完全是太大了。即使是汗液传感技术中最新的贴片或纹身技术也需要几微升的生物液，导致采样间隔很慢(10‘S需要几分钟甚至几个小时)。如果汗液传感的最大论点之一是持续监测的可能性，那么显然迫切需要找到强大而简单的方法，将最微小的汗液(纳米升)持续带到传感器中。这绝不是一个简单的挑战，因为皮肤表面高度多变，存在许多可能会混淆汗液采样的因素。如果能够开发这种技术，回报可能是巨大的，允许：(1)与血液的相关性最快可达2分钟。时间分辨率；(2)对于久坐的使用者，每天有更多的天然汗液采样事件；(3)对于化学刺激汗液，与商业产品相比，化学刺激剂的用量减少了100倍；(4)重要的是，减少了来自死皮表面的混杂污染。显然，改进汗液采样是一项值得研究人员关注的中心挑战。此外，这样的研究课题也是通过将研究与高中和本科学生的研究和教学相结合来培养和激励下一代科学家和工程师的理想选择。这项NSF提案的具体目标是首次创造出以分钟级分辨率实现按时间关联的汗感的能力。该提议的核心假设是，通过微流体的巧妙相互作用，小汗管和传感器之间的流体体积可以从1‘S微升减少到10’S纳米升(10-100倍)，从而在新汗液到达传感器之前只有几分钟的时间。进行这一假设的理由很简单，汗液传感在患者和健康监测、体育运动、狭窄治疗范围的药物监测等方面具有巨大的上行潜力，但除非可以使用更低的出汗率、更快的采样时间和减少皮肤表面的分析物污染，否则无法充分发挥其潜力。该建议还通过：(1)创建时间模型，预测离子、分子和蛋白质分析物从血液中分配到汗液和传感器上的时间；(2)将最小生物流体采样和传感的前沿从微升推进到纳升；(3)通过实验验证所创建的模型和技术，从而点燃对汗液传感科学和技术的进一步追求。

Among non-invasive wearable technologies with a large upside potential, sweat sensing technology is arguably the most underdeveloped. Even so, excitement is building, as many sweat electrolytes, metabolites, amino acids, proteins, and other biomarkers are showing promise for monitoring both mental and physical status and/or disease. However, unfortunately many of the commercially available technology solutions that could be used for sweat require ~10's of microliters sample volumes, which are entirely too large for continuous sweat analysis. Even the latest patch or tattoo advances in sweat sensing technology require several microliters of biofluid, resulting in slow sampling intervals (10's of minutes or even hours). If one of the biggest arguments for sweat sensing is the potential for continuous monitoring, then there is a clear and pressing need to discover powerful yet simple methods to continuously bring the tiniest amounts of sweat (nanoliters) to sensors. This is by no means a simple challenge, as the skin surface is highly variable and presents numerous factors that can confound sweat sampling. If such technology could be developed the payoff could be huge, allowing: (1) correlations with blood with as fast as ~2 min. time resolution; (2) for sedentary users, more sampling events per day of natural sweat; (3) for chemically stimulated sweat, a 100X reduction in the amount of chemical stimulant delivered compared to commercial products; (4) importantly, reducing confounding contamination coming from the dead skin surface. Clearly, improved sweat sampling is a central-challenge worthy of attention by researchers. Furthermore, such a research topic is also ideal for cultivating and inspiring the next generation of scientists and engineers through integration of research with both high-school and undergraduate student research and teaching.The specific objective of this NSF proposal is to create for the first time, the ability to achieve chronologically correlated sweat sensing with minute-level resolution. The proposal's central hypothesis is that through a clever interplay of microfluidics, the fluidic volume between eccrine sweat ducts and sensors can be reduced from ~1's of microliters down to 10's of nanoliters (10-100X), resulting in only minutes before new sweat reaches the sensors. The rationale for pursuing this hypothesis is simple, sweat sensing has enormous upside potential for applications in patient and wellness monitoring, athletics, narrow therapeutic-range pharmaceutical monitoring, etc., but cannot reach its full potential unless lower sweat rates can be used, faster sampling times enabled, and analyte contamination from the skin surface mitigated. The proposal also advances knowledge in sweat sensing science by: (1) creating temporal models which predict the time for partitioning of ionic, molecular, and protein analytes from blood, into sweat, and onto the sensors;(2) advancing the frontiers of minimum biofluid sampling and sensing from the microliter to the nanoliter regime;(3 experimentally validating both the created models and technology, and therefore igniting further pursuit of sweat sensing science and technology.