Rapid, disposable, nucleic acid diagnostic device for multiplexed point of care f

描述(申请人提供)：快速准确地识别高传染性和致病性疾病，对于及早预测暴发风险和有效部署医疗和行政对策至关重要。不幸的是，目前在护理点(POC)使用的诊断方法主要是免疫学分析，通常缺乏足够的敏感性、特异性和多重能力来进行准确的早期诊断。已开发或正在开发的基于核酸的诊断产品需要一种相对昂贵的专用仪器，这种仪器往往使小型诊所和资源有限的环境望而却步，不适合大流行的高容量需求。我们建议开发一种无仪器、自给自足、低成本(20美元/台)、一次性、快速(30分钟，样本到答案)的核酸POC诊断设备(MTIDx)，能够检测甲型流感、乙型流感、呼吸道合胞病毒和RNaseP内部控制(4-plex)。最终的MTIDx产品被设计为FDA批准的、CLIA豁免的(1988年临床实验室改进修正案)基于核酸(NA)的诊断设备，用于分析人类鼻拭子样本。MTIDx(多目标识别诊断)将是一款口袋大小的设备，操作简单，只需最少的用户干预，还可以选择由9V电池供电，用于资源有限/现场设置。它将适用于大批量生产，允许快速生产数百万台，以满足疫情爆发期间的激增产能。该诊断系统将梅萨科技的核酸提取、快速放大、基于横向流动的(基于LF的)比色检测组件与简单的流体控制和微加热器解决方案集成到一个易于使用、低成本的一次性设备中。在第一阶段项目中，我们通过快速成型的方法成功地开发了集成器件。该第二阶段项目的工作将集中于第一阶段设计的优化，以包括更精细的设计，以实现低复杂性、CLIA波形的产品，以及成本效益和环境友好的可重复使用电子电路元件概念，从而允许在POC进行广泛和快速的适应。我们将进一步优化冻干试剂的开发，以确保环境储存的兼容性，开发稳定的缓冲试剂和胶囊方法，设计制造优化方案，并对临床样本进行性能评估。主要的第二阶段交付内容是MTIDx Ready for Manufacturing(面向制造的设计)的设计，在后续制造、FDA和标记工作之前的30分钟内提供样本到答案的4路诊断测试(流感A、流感B、RSV和RNaseP对照)。

DESCRIPTION (provided by applicant): Rapid and accurate identification of highly infectious and pathogenic disease is extremely important for the early forecast of outbreak risk and the effective deployment of medical and administrative countermeasures. Unfortunately, current diagnostics for use at the point-of-care (POC) are largely immunological assays that often lack adequate sensitivity, specificity, and multiplex capacity for an accurate early diagnosis. Nucleic acid- based diagnostic products developed or under development requires a relatively expensive dedicated instrument that is often prohibitive to small clinics and resource-limited settings and unsuitable for pandemic high capacity demand. We propose to develop an instrumentation-free, self-contained, low cost (<$20/unit), disposable, rapid (<30 minute, sample-to-answer), nucleic acid POC diagnostic device (MTIDx) capable of detecting influenza A, influenza B, RSV and RNaseP internal control (4-plex). The final MTIDx product is designed to be a FDA approved, CLIA-waived (Clinical Laboratory Improvement Amendments of 1988) nucleic acid (NA)-based diagnostic device for analyzing human nasal swab samples. MTIDx (Multiple Target Identification Diagnostic) will be a pocket-sized, device that is easy to operate with minimal user-intervention and also has an option to be powered by a 9V battery for use in resource-limited/field settings. It will be suitable for high volume manufacturing allowing rapid production of millions of units to meet surge capacity during an epidemic outbreak. The diagnostic system is based on the integration of Mesa Tech's proprietary technologies of nucleic acid extraction, rapid amplification, lateral flow-based (LF-based) colorimetric detection components with simple fluid control and microheater solutions into one easily used, low cost, disposable device. In Phase 1 project, we have successfully developed of integrated device through a rapid prototyping approach. Work in this Phase II project will focus on the optimization of Phase I design to include more refined design for a low complexity, CLIA-waved product as well as cost effective and environment friendly reusable electronic circuit component concept that allows the wide and rapid adaption at POC. We will further optimize the development of lyophilized reagents to confer ambient storage compatibility, development of stable buffer reagents and capsulation methods, design for manufacturing optimizations and conduct performance evaluation on clinical samples. The primary Phase II deliverable is the design of MTIDx ready for manufacturing (Design For Manufacturing) that offers a sample-to-answer 4-plex diagnostic test (Flu A, FluB, RSV, and RNase P control) under 30 minutes prior to the follow up manufacturing, FDA and marking effort.