A New Approach to Autonomous Point-of-care Tropical Disease Diagnostics Using Sol

描述（由申请人提供）：在这个项目中，我们建议开发用于热带疾病感染的即时诊断的太阳能热微流体。利用这项技术，我们 相信有可能从复杂的生物样本（如呕吐物）中提取和检测纯化、浓缩的霍乱毒素，只需要创造性地操纵环境阳光。显然需要易于使用的诊断测试，可以快速筛选复杂的样本，如粪便或呕吐物，以寻找与热带疾病相关的广泛的细菌和病毒。传统上，这已经使用“简单”的易于使用的诊断方法，例如试纸测定法来完成。这些是受欢迎的，因为它们只需要插入样品，并且流体输送、样品处理和检测反应都自动发生，而无需用户或外部电源的进一步输入。虽然对于在简单样品（例如尿液中的hCG）上进行简单检测测定非常成功，但当应用于检测更复杂样品基质中的稀有靶标时，它们往往表现出非常差的临床灵敏度/特异性。缩小性能和临床要求之间的差距的大多数尝试涉及结合更复杂的微流体，以更好地处理/浓缩样品，以及超灵敏的纳米生物传感器，以检测较低水平的靶标。虽然这些方法确实具有更好的临床性能，但增加的复杂性、成本和自主性的丧失与使“简单”测定流行的原因形成了直接对比。在这里，我们提出，“太阳能热”微流体可以促进复杂的样品处理的方式，是准自主的，易于操作，并且不需要任何外部能量输入超出环境阳光。简而言之，该技术涉及放置在微流体芯片和入射阳光之间的简单荫罩，其在芯片上诱导明确的热图案。我们表明，通过创造性地安排这些热模式，可以实现复杂的样品处理操作，包括：（1）热泳样品过滤，（2）热润湿触发的微流体传输，和（3）分子特定浓度后的热释放。用户只需将荫罩点击到新位置，即可在测定中的不同阶段之间切换。我们在这个提案中的目标是发展太阳能热微流体样品处理背后的基础科学，并证明它可以用于从合成呕吐物样品中提取和浓缩霍乱毒素B。

DESCRIPTION (provided by applicant): In this project we propose to develop solar-thermal microfluidics for point-of-care diagnostics of tropical disease infections. Using this technique we believe it possible to extract and detect purified, concentrated, cholera toxin from a complex biosample, like vomit, using nothing more than creative manipulation of the ambient sunlight. A clear need exists for easy-to-use diagnostic tests that can rapidly screen complex samples, like stool or vomit, for a broad swath of bacteria and viruses associated with tropical diseases. Traditionally this has been done using "simple" easy to use diagnostics, such dipstick assays. These are popular because they require only the insertion of the sample and the fluid transport, sample processing, and detection reaction all occur autonomously without further input from the user or external power. While extremely successful for performing simple detection assays on simple samples (e.g. hCG in urine), when applied to the detection of rarer targets in more complex sample matrices they tend to exhibit very poor clinical sensitivity/specificity. Most of th attempts to close the gap between performance and clinical requirements have involved the incorporation of more complex microfluidics, to better process/concentrate the sample, and ultrasensitive nanobiosensors, to detect the target at lower levels. While these approaches do have better clinical performance, the added complexity, cost, and loss of autonomy stand in direct contrast with what makes the "simple" assays popular. Here we propose that "solar-thermal" microfluidics can facilitate complex sample processing in a way that is quasi-autonomous, easy to operate, and does not require any external energy input beyond ambient sunlight. Put simply, the technique involves a simple shadow mask placed between a microfluidic chip and the incident sunlight that induces a well-defined thermal pattern on the chip. We show that by creative arrangement of these thermal patterns complex sample processing operations can be achieved including: (1) thermo-phoretic sample filtration, (2) thermo-wetting triggered microfluidic transport, and (3) thermal-release following molecularly specific concentration. A user switches between different stages in the assay simply by clicking the shadow mask into a new position. Our goal in this proposal is to develop the fundamental science behind solar-thermal microfluidic sample processing and demonstrate that it can be used to extract and concentrate cholera toxin B from a synthetic vomit sample.