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、灵敏，并且能够检测症状前和症状标志物，以进行特定诊断，从而实现有效的对策，包括治疗干预。这样的系统还必须易于使用、自动化和独立，并且优选地具有小的占地面积以允许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，用于筛选可能暴露于生物毒素的个人。该装置将进行快速的基于微流控芯片的免疫测定（< 3-10分钟），具有低样品体积要求（10 uL）和可观的灵敏度（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来促进免提分析，以快速测量最低程度预处理的体液中的分析物浓度。微流体芯片与小型化电子器件、光学元件（例如二极管激光器）、流体处理组件、数据采集软件和用户界面集成以创建便携式自包含装置。该设备能够同时检测暴露于多种毒素的症状前和症状生物标志物（每个芯片多达32种分析物）。该器械有可能用于分类、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。验证将涉及检测外源性人血清和粘液样本以及选定毒素中毒动物样本。开发的技术和知识产权将转让给商业合作伙伴，用于该设备的中试规模制造。我们还将与我们的商业合作伙伴实施产品开发计划，为获得监管许可做准备。所述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（例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.