Rapid and Cost-Effective Diagnostic System for Sexually Transmitted Infections

快速且经济高效的性传播感染诊断系统

• 批准号: 8199260
• 负责人: JOHN E MUELLER
• 金额: $ 19.97万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-05 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199260
• 关键词: Address; Advanced Development; Aerosols; Affect; Architecture; Bedside Testings; Biological Assay; Centers for Disease Control and Prevention (U.S.); Chlamydia; Chlamydia trachomatis; Clinic; Clinical; Collaborations; Communities; Consult; Consultations; Coupled; DNA; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Ectopic Pregnancy; Epidemic; Gonorrhea; Health; Health Care Costs; Health care facility; Healthcare; Heating; Infection; Infertility; Jail; Lateral; Left; Methods; Microbiology; Microfluidics; Molecular; National Institute of Allergy and Infectious Disease; Neisseria gonorrhoeae; North Dakota; Nucleic Acids; Patients; Pelvic Inflammatory Disease; Performance; Phase; Polymerase Chain Reaction; Preparation; Prevalence; Public Health; Reading; Reporting; Reproducibility; Research; Rest; Sampling; Screening procedure; Sepsis; Sexually Transmitted Diseases; Source; Syringes; System; Technology; Test Result; Testing; Texas; Tube; Universities; Visit; Work; commercialization; cost; cost effective; design; design and construction; detention center; improved; innovation; innovative technologies; instrumentation; nanomaterials; novel; outreach; pathogen; point of care; prototype; rapid diagnosis; tool; Address; Advanced Development; Aerosols; Affect; Architecture; Bedside Testings; Biological Assay; Centers for Disease Control and Prevention (U.S.); Chlamydia; Chlamydia trachomatis; Clinic; Clinical; Collaborations; Communities; Consult; Consultations; Coupled; DNA; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Ectopic Pregnancy; Epidemic; Gonorrhea; Health; Health Care Costs; Health care facility; Healthcare; Heating; Infection; Infertility; Jail; Lateral; Left; Methods; Microbiology; Microfluidics; Molecular; National Institute of Allergy and Infectious Disease; Neisseria gonorrhoeae; North Dakota; Nucleic Acids; Patients; Pelvic Inflammatory Disease; Performance; Phase; Polymerase Chain Reaction; Preparation; Prevalence; Public Health; Reading; Reporting; Reproducibility; Research; Rest; Sampling; Screening procedure; Sepsis; Sexually Transmitted Diseases; Source; Syringes; System; Technology; Test Result; Testing; Texas; Tube; Universities; Visit; Work; commercialization; cost; cost effective; design; design and construction; detention center; improved; innovation; innovative technologies; instrumentation; nanomaterials; novel; outreach; pathogen; point of care; prototype; rapid diagnosis; tool

DESCRIPTION (provided by applicant): According to the CDC, chlamydia and gonorrhea, caused by Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), respectively, are the first and second most frequently reported STIs in the US and likely the rest of the world. These STIs are often under-diagnosed, leading to delayed treatment, continued spread and higher public healthcare costs (~$14.7 billion annually). As a result of their prevalence and long term health consequences, there is a need for rapid, sensitive methods of detecting STIs in order for patients to get results and treatment immediately. It is important that patients receive test results and initial consultation or treatment during the first patient visit, as they rarely return for a second visit. Point-of-care (POC) tests are an important strategy to address the STI epidemic, and because many affected by STIs (young and/or poor) often have limited access to traditional healthcare, POC tests that can be performed in non-traditional settings (university clinics, community public health care clinics, jails, detention centers) could greatly reduce STIs. The aim of this proposal is to develop a rapid, easy-to-use, inexpensive diagnostic system for identifying STI pathogens such as CT and NG. The system will combine Lynntech's novel nucleic acid amplification and lateral flow detection devices and can be used in many non-traditional healthcare settings. In Phase I, a high performance, low-cost thermal gradient cycler (TGC) will be developed. It will perform rapid polymerase chain reaction (PCR) for CT/NG targets in a simplified architecture that creates a stable thermal gradient from a single heat source. It addresses problems common to many thermal cyclers, such as user interfacing, sample loading, reliability and reproducibility. The TGC will be coupled with a lateral flow strip component for detecting PCR amplicons, and this component is incorporated into a standard 0.2-mL PCR tube, which is used in the TGC during PCR. This elegant integration allows the amplification and detection to be performed in a closed system, eliminating post- PCR contamination, and it permits a non-technical user to easily read and interpret results without sample transfer or special instrumentation. It will be demonstrated that the entire assay can be completed in less than 45 min, including sample preparation. When combined with an appropriate sample preparation module (also being developed by Lynntech), the system could serve as a POC device for rapid diagnosis of STIs. The proposed work will be carried out in collaboration with experts from various fields, including Charlotte Gaydos (STI expert, Johns Hopkins University), GuoDong Liu (nanomaterials and lateral flow assay, North Dakota State University), Victor Ugaz (fluidic/thermal characterization, Texas A&M University), and Yi-Wei Tang (clinical sample preparation, Vanderbilt University). To assist with technology commercialization, Diagnostic Consulting Network, Inc will provide consultation, as they have expertise in lateral flow assay design and manufacturing. The successful development and commercialization of our technology will impact how sophisticated molecular diagnostic assays can be implemented in POC or non-traditional healthcare settings. PUBLIC HEALTH RELEVANCE: Chlamydia and gonorrhea are the most common sexually transmitted infections (STIs) in the US, causing serious long term health problems such as sepsis, stricture disease, pelvic inflammatory disease (PID), ectopic pregnancy and infertility. This project will advance the development of a POC molecular diagnostic device for the rapid and inexpensive screening of STIs in non-traditional healthcare settings. Lynntech will build a very low cost ($75 parts), automated thermal gradient cycler (TGC) to perform up to 16 polymerase chain reactions in less than 25 min. Additionally, Lynntech will combine this TGC technology with a lateral flow test technology for PCR amplicon detection. This low cost (<$2), 5-min lateral flow disposable device is specifically designed to perform "closed-tube" molecular detection. If properly coupled with a sample preparation method, these two innovative technologies will yield a 45-min molecular test to identify STI pathogens in order for patients to receive immediate treatment before they leave a healthcare facility.

描述（由申请人提供）：根据CDC，衣原体和淋病，由沙眼衣原体（CT）和Neisseria Gonorrhoeae（NG）造成，是美国的第一和第二经常报告的性传播感（NG）。这些性传播感染通常被诊断出来，导致治疗延迟，持续差异和更高的公共医疗费用（每年约147亿美元）。由于其患病率和长期健康后果，需要快速，敏感的方法检测性传播感染，以便患者立即获得结果和治疗。重要的是，患者在第一次患者就诊期间接受测试结果和初步咨询或治疗很重要，因为他们很少返回第二次访问。护理点（POC）测试是解决性病流行的重要策略，因为许多受传播感染的影响（年轻人和/或穷人）通常在非传统环境中可以进行的传统医疗保健，POC测试（大学诊所，社区公共保健诊所，监狱，监狱，疏忽中心）可以大大降低Stis。该提案的目的是开发一个快速，易于使用，廉价的诊断系统，用于识别STI病原体，例如CT和NG。该系统将结合Lynntech的新型核酸扩增和横向流动检测装置，可用于许多非传统医疗保健环境。在第一阶段，将开发出高性能的低成本热梯度循环器（TGC）。它将在简化的体系结构中对CT/ng靶标进行快速聚合酶链反应（PCR），从而从单个热源产生稳定的热梯度。它解决了许多热循环器常见的问题，例如用户接口，样品加载，可靠性和可重复性。 TGC将与用于检测PCR扩增子的侧向流条件耦合，并将该组件掺入标准的0.2-mL PCR管中，该管子在PCR期间在TGC中使用。这种优雅的集成允许在封闭的系统中进行放大和检测，从而消除了PCR后污染，并允许非技术用户轻松读取和解释结果，而无需样品传输或特殊仪器。可以证明，整个测定法可以在不到45分钟的时间内完成，包括样品制备。当与适当的样品制备模块（也是由Lynntech开发的）时，该系统可以用作快速诊断性传播感染的POC装置。拟议的工作将与来自各个领域的专家合作进行，包括夏洛特·盖多（Charlotte Gaydos）（STI专家，约翰·霍普金斯大学（Johns Hopkins University），朱旺·刘（Guodong Liu）（纳米材料和北达科他州立大学的侧向流程测定法），维多利亚·ugaz（Victorig/Themal Tarricization，Texas A＆M University，Texas A＆M University）和Yi-Wei-weici tank（Yi-Wei tank）（vickas and themiald）（victoric ugaz）（Victoric ugaz）。为了协助技术商业化，诊断咨询网络公司将提供咨询，因为它们在侧向流量测定设计和制造方面具有专业知识。我们技术的成功开发和商业化将影响如何在POC或非传统医疗保健环境中实施复杂的分子诊断测定法。 公共卫生相关性：衣原体和淋病是美国最常见的性传播感染（STI），造成了严重的长期健康问题，例如脓毒症，狭窄疾病，骨盆炎性疾病（PID），异常妊娠和不育。该项目将推动开发POC分子诊断装置，以快速且廉价地筛选非传统医疗保健环境中的性传播感染。 Lynntech将建立非常低的成本（$ 75零件），自动梯度循环仪（TGC），在不到25分钟的时间内执行多达16个聚合酶链反应。此外，Lynntech将把这种TGC技术与用于PCR扩增子检测的侧向流程测试技术相结合。这种低成本（<$ 2），5分钟的侧向流动设备是专门设计用于执行“闭管”分子检测的。如果与样品制备方法正确结合，这两种创新技术将产生45分钟的分子测试，以识别STI病原体，以便患者在离开医疗机构之前立即接受治疗。