Microfluidic Platform for Multiplexed Diagnostics

用于多重诊断的微流控平台

• 批准号: 8535603
• 负责人: Anup K. Singh
• 金额: $ 90.69万
• 依托单位: SANDIA CORP-SANDIA NATIONAL LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8535603
• 关键词: Ally; Animal Model; Animals; Anthrax disease; Antibodies; Beds; Benchmarking; Biological; Biological Assay; Biotechnology; Blood; Botulinum Toxins; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinic; Clinical; Consumption; Contracts; Detection; Development; Development Plans; Devices; Diagnosis; Diagnostic; Disease; Disease Marker; Disease Outbreaks; Enterotoxins; FDA approved; Face; Goals; Gold; Health; Heart Diseases; Hospitals; Human; Immunoassay; Individual; Infection; Institution; Intoxication; Laboratories; Laboratory Personnel; Legal patent; Liquid substance; Malignant Neoplasms; Measures; Medical; Methods; Microfluidics; Military Personnel; Mucous body substance; Mus; National Institute of Allergy and Infectious Disease; National Security; Nose; Performance; Plastics; Population; Preparation; Primary Health Care; Production; Public Health; Reagent; Research; Ricin; Saliva; Sampling; Satellite Hospitals; Serotyping; Serum; Shiga-Like Toxins; Site; Swab; System; Systemic disease; Testing; Texas; Therapeutic Intervention; Time; Toxin; Transportation; United States Department of Agriculture; Universities; Urine; Whole Blood; Work; assay development; base; blind; cost; cross reactivity; design; driving force; instrument; mouse model; multidisciplinary; next generation; novel marker; pathogen; point of care; product development; prototype; screening

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.

描述（由申请人提供）：迫切需要开发下一代临床诊断设备，用于筛查暴露于生物威胁剂和/或中毒的个体。这些设备需要能够进行快速、灵敏和特异性的诊断，以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，并且最好具有较小的占地面积，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 Invetech 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。该设备旨在用于海外初级保健机构、公共卫生实验室和军事诊所，用于检测临床样本中的 NIAID 优先病原体和毒素肉毒杆菌、炭疽、蓖麻毒素、志贺样毒素和葡萄球菌肠毒素 B (SEB)。 Invetech 将设计和开发 Beta 原型，准备在桑迪亚和两个独立实验室进行现场测试，使用加标的人体样本以及中毒/感染小鼠的血清和鼻拭子。 该设备的试验台版本已被证明可以对包括生物毒素在内的多种分析物进行超灵敏检测（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的灵敏度高约 100 倍）。该装置利用离心力驱动流在塑料盘中实施基于微珠的夹心免疫测定和活性测定，并且可以使用几μL的临床样品快速（<10分钟）和灵敏地（〜fM）检测多种分析物。该诊断设备由于其基于珠子的检测形式，很容易适用于检测其他病原体和疾病标志物。该设备无需进行设备外样品制备，并且与多种体液兼容，包括全血、血清、唾液和尿液。 我们组建了一支多学科团队来开发、制造和测试 SpinDx，除了 Sandia、Invetech 和 Bio-Rad 之外，还包括两家开发中毒/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地区研究中心 (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 Allied Health 医院实验室和 USDA-WRRC 两个对该设备进行独立、盲测的地点。