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

用于多重护理点的快速、一次性核酸诊断装置

• 批准号: 8199470
• 负责人: HONG CAI
• 金额: $ 29.82万
• 依托单位: MESA TECH INTERNATIONAL, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199470
• 关键词: Adenoviruses; Amendment; Biological Assay; Buffers; Cellular Phone; Chemistry; Clinic; Clinical; Cytolysis; Data; Detection; Development; Devices; Diagnostic; Diagnostic tests; Disease; Disease Outbreaks; Dyes; Early Diagnosis; Engineering; Enzymes; Epidemic; FDA approved; Future; Generations; Human; Influenza; Injection of therapeutic agent; International; Intervention; Laboratories; Lateral; Liquid substance; Lung diseases; Medical; Methods; Microspheres; Molds; Molecular Diagnostic Testing; Nose; Nucleic Acids; Parainfluenza; Performance; Phase; Preparation; Process; Production; Protocols documentation; RNase P; Reagent; Relative (related person); Resources; Respiratory syncytial virus; Risk; Running; Sampling; Scientist; Sensitivity and Specificity; Small Business Innovation Research Grant; Solutions; Swab; System; Systems Integration; Technology; Temperature; Testing; Work; base; cost; design; flu; innovation; instrument; instrumentation; internal control; meetings; pandemic disease; point of care; point-of-care diagnostics; prototype; sample collection; stability testing

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 (<40 minute, sample-to-answer), nucleic acid POC diagnostic device (MTIDx) capable of detecting influenza A, influenza B, RSV and other relative respiratory diseases. 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 cell phone-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 a pandemic 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 preliminary data, we have demonstrated the feasibility of integrated device approach through a laboratory prototype. Work in this Phase I SBIR proposal will focus on the optimization of system integration and the refinement of initial MTIDx laboratory prototype designs to facilitate the transition of laboratory prototypes to manufacture-ready designs. Existing prototype designs will be transitioned to injection- molded prototypes to enable short-run production for rigorous characterization and laboratory testing. We will also incorporate the development of lyophilized reagents for amplification and detection to confer ambient storage compatibility, development of stable buffer reagents and capsulation methods, design for manufacturing optimizations to facilitate future high volume production and initial testing to identify design refinements required to attain performance objectives. The primary Phase I deliverable is the demonstration of an integrated MTIDx DFM-prototype (Design For Manufacturing) that offers a sample-to-answer 4-plex diagnostic test (Flu A, B, RSV and RNaseP as a control) complete in <40 minutes. In a follow-on Phase 2 project, we will incorporate more disease targets, further optimize the manufacture-ready designs, produce injection-molded devices and validate performance on a large panel of well-characterized clinical samples. PUBLIC HEALTH RELEVANCE: To better protect the public from potentially deadly pandemic/epidemic outbreaks, we will develop an instrumentation-free, self-contained, easy-to-use, low cost (<$20/unit), disposable, rapid (<40 minute, sample-to-answer), nucleic acid-based POC diagnostic device (MTIDx) capable of detecting influenza A, influenza B, RSV and RNase P (as an internal control). 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. This cell phone-sized, device will be compatible with high volume manufacturing and also an option to be powered by a 9V battery for use in resource- limited/field settings.

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以及有效部署医疗和行政对策至关重要。不幸的是，目前用于护理点（POC）的诊断主要是免疫测定，其通常缺乏足够的灵敏度、特异性和用于准确早期诊断的多重能力。已开发或正在开发的基于核酸的诊断产品需要相对昂贵的专用仪器，这通常对小诊所和资源有限的环境是禁止的，并且不适合大流行的高容量需求。我们提出开发一种免仪器、独立、低成本（<20美元/单位）、一次性、快速（<40分钟，采样-应答）、核酸POC诊断装置（MTIDx），其能够检测甲型流感、乙型流感B、RSV和其他相关呼吸道疾病。最终MTIDx产品设计为FDA批准的CLIA豁免（1988年临床实验室改进修正案）基于核酸（NA）的诊断器械，用于分析人鼻拭子样本。MTIDx（多目标识别诊断）将是一个手机大小的设备，易于操作，用户干预最少，还可以选择由9V电池供电，用于资源有限/现场设置。它将适合大批量生产，允许快速生产数百万个单位，以满足大流行爆发期间的激增产能。该诊断系统基于梅萨科技公司的专有技术核酸提取，快速扩增，基于侧流（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，一次性设备。在初步数据中，我们已经通过实验室原型证明了集成器件方法的可行性。第一阶段SBIR提案的工作重点是系统集成的优化和初始MTIDx实验室原型设计的改进，以促进实验室原型向可重复使用设计的过渡。现有的原型设计将过渡到注塑成型原型，使短期生产的严格表征和实验室测试。我们还将开发用于扩增和检测的冻干试剂，以赋予环境储存相容性，开发稳定的缓冲试剂和封装方法，设计生产优化，以促进未来的大批量生产和初步测试，以确定达到性能目标所需的设计改进。第一阶段的主要交付成果是集成MTIDx DFM原型（面向制造的设计）的演示，该原型可提供在40分钟内完成的样本到答案的4重诊断检测（Flu A、B、RSV和RNaseP作为质控品）。在后续的第二阶段项目中，我们将纳入更多的疾病靶点，进一步优化可植入设计，生产注塑成型设备，并在大量表征良好的临床样本上验证性能。 公共卫生相关性：为了更好地保护公众免受可能致命的大流行/流行病爆发的影响，我们将开发一种免仪器、独立、易于使用、低成本（<20美元/单位）、一次性、快速（<40分钟，样本到答案）、基于核酸的POC诊断设备（MTIDx），能够检测甲型流感、B流感、RSV和RNase P（作为内部对照）。最终MTIDx产品设计为FDA批准的CLIA豁免（1988年临床实验室改进修正案）基于核酸（NA）的诊断器械，用于分析人鼻拭子样本。这种手机大小的设备将与大批量生产兼容，并且还可以选择由9V电池供电，用于资源有限/现场设置。