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

描述（由申请人提供）：快速准确地识别高传染性和致病性疾病对于早期预测爆发风险和有效部署医疗和行政对策极为重要。不幸的是，目前在医疗点（POC）使用的诊断主要是免疫检测，往往缺乏足够的敏感性、特异性和多重能力，无法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，这对于小型诊所和资源有限的环境来说往往是望而却步的，也不适合大流行的高容量需求。我们建议开发一种无需仪器、独立、低成本（< 20美元/台）、一次性、快速（<30分钟，从样品到答案）的核酸POC诊断装置（MTIDx），能够检测甲型流感、乙型流感、RSV和RNaseP内控（4-plex）。最终的MTIDx产品被设计为FDA批准，clia豁免（1988年临床实验室改进修正案），用于分析人类鼻拭子样本的核酸（NA）诊断设备。MTIDx（多目标识别诊断）将是一种口袋大小的设备，操作简单，用户干预最少，还可以选择由9V电池供电，用于资源有限/现场环境。它将适合大批量生产，允许快速生产数百万个单位，以满足流行病爆发期间的激增能力。该诊断系统基于Mesa Tech的核酸提取、快速扩增、基于侧流（fl -based）的比色检测组件与简单的流体控制和微加热器解决方案的专有技术集成为一个易于使用、低成本的一次性设备。在一期项目中，我们通过快速原型方法成功开发了集成器件。第二阶段项目的工作将集中在第一阶段设计的优化上，包括更精细的低复杂性设计，clia波产品，以及成本效益和环境友好的可重复使用的电子电路元件概念，使POC能够广泛和快速地适应。我们将进一步优化冻干试剂的开发以获得环境储存兼容性，开发稳定的缓冲试剂和胶囊化方法，设计生产优化并对临床样品进行性能评估。II期交付的主要产品是准备生产的MTIDx设计（为生产而设计），在后续生产，FDA和标记工作之前30分钟内提供样品到答案的4-plex诊断测试（流感a，流感b， RSV和rna酶P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.