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。这些设备需要能够进行快速、灵敏和特异性诊断，以实现有效的对策，包括治疗干预。这种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。我们的目标是与我们的商业合作伙伴Investech和Bio-Rad一起开发一种可制造和可商业化的设备（SpinDx），为向FDA提交510（k）做准备。该器械预期用于海外的初级保健机构、公共卫生实验室和军事诊所，用于检测临床样本中NIAID优先级病原体和毒素肉毒杆菌、炭疽、蓖麻毒素、志贺样毒素和葡萄球菌肠毒素B（SE B）。Investech将设计和开发Beta原型，准备在桑迪亚和两个独立的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。 该设备的测试台版本已经被证明可以对包括生物毒素在内的许多分析物进行超灵敏检测（例如，我们对肉毒杆菌毒素A的测定比金标准小鼠生物测定灵敏约100倍）。该设备使用离心力驱动的流动，以实现珠为基础的夹心免疫测定和活性测定在一个塑料盘，并可以快速（<10分钟）和灵敏度（~ fM）检测多种分析物使用几个？L临床样本。该诊断装置由于其基于珠的测定形式，易于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的样品制备，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，其中除了Sandia、Investech和Bio-Rad之外，还包括两个开发中毒/感染动物模型的机构-美国农业部西部地区研究中心（USDA-WRRC）和德克萨斯州加尔维斯顿的德克萨斯大学医学分支（UTMB）; UTMB联合健康医院实验室和USDA-WRRC的两个研究中心对该器械进行了独立的盲态测试。

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.