Rapid Molecular Detection of Tuberculosis without PCR amplification

无需 PCR 扩增即可快速进行结核病分子检测

• 批准号: 9347344
• 负责人: Alfredo Andres Celedon
• 金额: $ 99.84万
• 依托单位: SCANOGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-13 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347344
• 关键词: Affect; Automobile Driving; Biochemical Reaction; Biological Assay; Cells; Characteristics; Clinical; Country; Cytolysis; Detection; Developed Countries; Developing Countries; Development; Devices; Diagnosis; Disease; Docking; Documentation; Ensure; Epidemic; Equipment; Evaluation; Goals; Healthcare Systems; Image Analysis; Methods; Microscopy; Molecular; Molecular Diagnostic Testing; Mycobacterium tuberculosis H37Rv; Patients; Performance; Pharmaceutical Preparations; Phase; Predisposition; Preparation; Price; Procedures; Production; Protocols documentation; Reagent; Reporting; Resources; Ribosomal RNA; Sampling; Scanning; Sexually Transmitted Diseases; Specificity; Sputum; System; Temperature; Testing; Tuberculosis; Validation; World Health Organization; base; design; extensive drug resistance; improved; instrument; killings; new technology; next generation; operation; point of care; portability; prototype; rapid detection; research clinical testing; resistant strain; single molecule; tool; tuberculosis drugs; usability

Project Summary Tuberculosis (TB) is a major global burden that kills 1.5 million people every year. TB mostly affects developing countries, but the rise of multi-drug and extensively drug resistant strains is a global threat. In order to control and eradicate this disease, it is imperative to have adequate tools to detect active TB in limited-resource settings and point-of-care (POC) settings, which is where most TB patients are seen. However, available detection methods have poor performance and are not suited for diagnosis in limited-resource or POC settings. The most commonly used method to detect TB is smear microscopy, a procedure developed more than 100 years ago that only detects 50% of the cases. In Phase I, we developed a sample preparation and detection procedure that is rapid, robust, easy to automate, and highly sensitive and specific. The new assay is based on Single Molecule Scanning (SMS), a novel technology capable of detecting single molecules using simple equipment. Here, we will develop a fully automated next generation molecular test based on the feasibility of SMS stablished in Phase I. The goal is to replace smear-microscopy for sputum- based diagnosis of TB in high TB-burden countries and to replace PCR-based TB diagnosis in developed countries. If successful, the new assay will be more accurate than the current leader molecular assay (>95% sensitivity, >99% specificity) and its price will be affordable for limited- resource settings ($6/test, $1,200/instrument). In addition, the new assay will satisfy all the characteristics that according to a WHO report are required in a product to replace smear microscopy. The overall goal of Phase II, is to develop and to validate a disposable cartridge and a fully automated instrument for TB testing. Aim 1 focuses on the development of the disposable cartridge, Aim 2 on the development of the portable instrument and Aim 3 on the verification and clinical validation of the final instrument and cartridge design. This evaluation together with the design documentation accumulated during the project will be combined with additional clinical evaluations to obtain CE mark, FDA approval, approval in high TB-burden countries, and the endorsement of the World Health Organization.

项目概要 结核病 (TB) 是全球的主要负担，每年导致 150 万人死亡。主要是结核病 影响发展中国家，但多重药物和广泛耐药菌株的增加是一个 全球威胁。为了控制和根除这种疾病，必须有足够的工具 在资源有限的环境和护理点 (POC) 环境中检测活动性结核病，这是 大多数结核病患者都见过。然而，现有的检测方法性能较差且 不适合在资源有限或 POC 环境中进行诊断。最常用的方法 检测结核病的方法是涂片显微镜检查，这是 100 多年前开发的一种方法，仅 检测到 50% 的病例。 在第一阶段，我们开发了一种快速、稳健、 易于自动化，并且高度敏感和具体。新的检测方法基于单分子 扫描（SMS），一种能够使用简单的方法检测单分子的新技术 设备。在这里，我们将基于以下技术开发全自动的下一代分子测试： 第一阶段确定了 SMS 的可行性。目标是取代痰涂片显微镜检查。 在结核病高负担国家进行基于 PCR 的结核病诊断，并在以下国家取代基于 PCR 的结核病诊断 发达国家。如果成功，新的检测将比当前领先的检测更准确 分子检测（>95% 灵敏度，>99% 特异性）及其价格对于有限的人来说是可以承受的 资源设置（6 美元/测试，1,200 美元/仪器）。此外，新的检测将满足所有 根据世界卫生组织的报告，替代涂片的产品需要具有以下特征 显微镜。 第二阶段的总体目标是开发并验证一次性墨盒和完全 结核病检测自动化仪器。目标 1 重点发展一次性用品 墨盒，目标 2 关于便携式仪器的开发，目标 3 关于验证和 最终仪器和墨盒设计的临床验证。本次评价与 项目期间积累的设计文件将与额外的临床相结合 获得 CE 标志、FDA 批准、结核病高负担国家批准以及 世界卫生组织的认可。