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护理点诊断的太阳能-热微流体。使用这项技术，我们 相信从复杂的生物样本(如呕吐物)中提取和检测纯化的浓缩霍乱毒素是可能的，只需创造性地操纵环境阳光即可。人们显然需要一种简单易用的诊断测试，这种测试可以快速筛查复杂的样本，如粪便或呕吐物，以检测与热带疾病相关的广泛细菌和病毒。传统上，这是通过“简单的”易于使用的诊断方法来完成的，比如试纸分析。这些方法很受欢迎，因为它们只需要插入样品，流体输送、样品处理和检测反应都是自动进行的，而不需要用户或外部电源的进一步输入。虽然对简单样本(例如尿液中的hCG)进行简单的检测分析非常成功，但当应用于检测更复杂的样本矩阵中的稀有目标时，它们往往表现出非常差的临床敏感性/特异性。为了缩小性能和临床要求之间的差距，大多数尝试都涉及加入更复杂的微流体，以更好地处理/浓缩样品，以及超灵敏的纳米生物传感器，以检测较低水平的目标。虽然这些方法确实有更好的临床表现，但增加的复杂性、成本和自主性的丧失与使“简单”分析流行的原因形成了直接对比。在这里，我们提出“光热”微流体可以促进复杂的样品处理，以一种准自主的方式，易于操作，不需要任何外部能量输入环境阳光以外的。简而言之，这项技术包括在微流控芯片和入射阳光之间放置一个简单的荫罩，在芯片上诱导出明确的热图案。我们发现，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)热发光样品过滤，(2)热润湿触发的微流控传输，(3)随分子特定浓度的热释放。用户只需将荫罩点击到新位置，即可在化验中的不同阶段之间切换。我们在这项提案中的目标是发展太阳能热微流控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.