Portable Microfluidic Platform for Biotoxin Diagnostics

描述（由申请人提供）：迫切需要开发下一代临床诊断设备，用于筛查暴露于和/或中毒于生物威胁剂的个体。这些设备需要快速、敏感，并能够检测症状前和症状标记物以进行特定诊断，从而实现包括治疗干预在内的有效对策。此类系统还必须易于使用、自动化和独立，并且最好占地面积小，以便在护理点和事件点设置中使用。我们建议开发一种便携式设备，用于筛选潜在暴露于生物毒素的个体。该设备将执行基于微流控芯片的快速免疫分析（< 3-10分钟），样品体积要求低（10 uL），灵敏度高（nM-fM）。我们的微流控方法通过将样品预处理（过滤，富集，混合）与电泳免疫测定相结合，促进了免提分析，以快速测量最低预处理体液中的分析物浓度。微流控芯片集成了小型化的电子器件、光学元件（如二极管激光器）、流体处理组件、数据采集软件和用户界面，以创建一个便携式、独立的设备。该设备能够同时检测暴露于多种毒素的症状前和症状性生物标志物（每个芯片多达32个分析物）。该设备具有分类、识别暴露模式和严重程度以及指导或监测包括治疗在内的对策的潜力。验证将涉及外源性人血清和粘液样本以及被选定毒素中毒的动物样本的测试。开发的技术和知识产权将转让给一个商业合作伙伴，用于该设备的中试规模生产。我们还将与我们的商业伙伴一起实施产品开发计划，为获得监管许可做准备。该诊断装置和方法还可以扩展到检测其他全身性疾病和病症如癌症和心血管疾病的生物标志物。

DESCRIPTION (provided by applicant): Urgent need exists for developing next-generation clinical diagnostics devices for screening individuals exposed to and/or intoxicated with biological threat agents. These devices need to be rapid, sensitive, and capable of detecting both presymptomatic and symptomatic markers for specific diagnosis to enable effective countermeasures including therapeutic intervention. Such systems must also be easy-to-use, automated and self-contained, and preferably, have a small footprint to allow use in point-of-care and point- of-incident settings. We propose to develop a portable device for screening individuals potentially exposed to biological toxins. The device will perform rapid microfluidic chip-based immunoassays (< 3-10 minutes) with low sample volume requirements (10 uL) and appreciable sensitivity (nM-fM). Our microfluidic method facilitates hands- free analysis by integrating sample pretreatment (filtering, enrichment, mixing) with electrophoretic immunoassays to quickly measure analyte concentrations in minimally pretreated bodily fluids. The microfluidic chip is integrated with miniaturized electronics, optical elements such as diode lasers, fluid- handling components, data acquisition software, and a user interface to create a portable, self-contained device. The device is capable of detecting presymptomatic and symptomatic biomarkers of exposure to multiple toxins simultaneously (up to 32 analytes per chip). The device has potential for triaging, identifying exposure mode and severity and directing or monitoring countermeasures including treatment. Validation will involve testing of exogenous human serum and mucus samples as well as samples from animals intoxicated with selected toxins. Technologies and intellectual properties developed will be transferred to a commercial partner for pilot-scale manufacturing of the device. We will also implement a product development plan with our commercial partner to initiate preparation for obtaining regulatory clearance. The diagnostic device and methods can also be extended to detection of biomarkers of other systemic diseases and conditions such as cancer and cardiovascular disease.