Microfluidic Platform for Multiplexed 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。这些设备需要能够快速、敏感和特定的诊断，以实现包括治疗干预在内的有效对策。这种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。我们的目标是与我们的商业合作伙伴Invetech和Bio-Rad一起开发可制造和商业化的设备（SpinDx），准备向FDA提交510(k)申请。该设备旨在用于初级保健机构、公共卫生实验室和海外军事诊所，用于检测NIAID优先病原体和毒素肉毒杆菌、炭疽、蓖麻毒素、志贺样毒素和临床样品中的葡萄球菌肠毒素B （SEB）。Invetech将设计和开发Beta原型，准备在Sandia和两个独立实验室进行现场测试，使用加标的人类样本以及中毒/感染小鼠的血清和鼻拭子。该设备的试验台版本已经被证明具有对包括生物毒素在内的许多分析物的超灵敏检测（例如，我们对肉毒杆菌毒素A的检测比金标准小鼠生物检测灵敏约100倍）。该设备使用离心力驱动的流动，在塑料圆盘中实现基于珠状三明治的免疫分析和活性分析，并且可以快速（<10分钟）和灵敏（~ fM）检测多种分析物。L的临床样本。该诊断装置由于其基于头部的检测格式，很容易适用于检测其他病原体和疾病标志物。该设备不需要设备外样品制备，并且与多种体液兼容，包括全血、血清、唾液和尿液。我们已经组建了一个多学科团队来开发、制造和测试SpinDx，除了Sandia、Invetech和Bio-Rad之外，还包括两个开发中毒/感染动物模型的机构——位于加利福尼亚州奥尔巴尼的美国农业部西部区域研究中心（USDA-WRRC）和位于德克萨斯州加尔维斯顿的德克萨斯大学医学分部（UTMB）；以及UTMB联合健康医院实验室和USDA-WRRC对该设备进行独立盲测的两个地点。

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 capable of rapid, sensitive, and 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. Our goal is to develop, with our commercial partners Invetech and Bio-Rad, a manufacturable and commercializable device (SpinDx) in preparation for 510(k) submission to the FDA. The device is intended for use in primary care facilities, public health labs, and military clinics overseas for detection of NIAID priority pathogens and toxins Botulinum, Anthrax, Ricin, Shiga-like toxin, and Staphyloccocus enterotoxin B (SEB) in clinical samples. Invetech will design and develop Beta prototypes ready for field-testing at Sandia and two independent laboratories using spiked human samples as well as serum and nasal swabs from intoxicated/infected mice. A test-bed version of the device has already been demonstrated with ultra-sensitive detection of a number of analytes including biotoxins (e.g., our assay for Botulinum toxin A is ~100-fold more sensitive than the gold-standard mouse bioassay). The device uses centrifugal force-driven flow to implement bead-based sandwich immunoassays and activity assays in a plastic disk, and can rapidly (<10 min) and sensitively (~ fM) detect multiple analytes using a few ?L of clinical sample. The diagnostic device, owing to its bead-based assay format, is readily adaptable to detection of other pathogens and disease markers. The device requires no off-device sample preparation and is compatible with multiple bodily fluids including whole blood, serum, saliva, and urine. We have assembled a multidisciplinary team for development, manufacturing and testing of SpinDx which includes, in addition to Sandia, Invetech and Bio-Rad, two institutions for developing animal models for intoxication/infection - United States Department of Agriculture's Western Regional Research Center (USDA-WRRC) in Albany, CA and University of Texas Medical Branch (UTMB) at Galveston, TX; and two sites for independent, blind testing of the device at UTMB Allied Health hospital lab and USDA-WRRC.