Ultracompact sample-to-answer nucleic acid test on USB stick

USB 记忆棒上的超紧凑样本到答案核酸测试

• 批准号: 1902503
• 负责人: Weihua Guan
• 金额: $ 30万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1902503&HistoricalAwards=false
• 关键词: Ultracompact; sample; answer; nucleic; acid; Ultracompact; sample; answer; nucleic; acid

Increased malaria control efforts have resulted in a dramatic reduction in the global malaria incidence over the past decade, and the World Health Organization has endorsed the ambitious goal of achieving worldwide malaria elimination and eradication. A change in focus from malaria control to malaria elimination requires easy and efficient ways to rapidly screen for malaria. Current malaria screening tests rely almost exclusively on microscopy and immunological tests. Both methods could miss significant information due to their limited detection abilities. Nucleic acid testing (NAT) is currently the most sensitive method available. Unfortunately, NAT-based methods developed to date mostly require certain infrastructures and skilled technicians. There is a critical need for an improved malaria screening test that combines the benefits of lateral flow-based testing (scalable throughput, minimal training) and the NATs (highly sensitive and specific). The success of the proposed research would enhance the health care system domestically and globally. As a platform technology, it would allow for delivering the highly sensitive test to remote, underserved and resource-limited communities. In addition, the proposed educational and outreach activity would foster student engagement through unique hands-on-experience-based interactive activities. The research objective of this proposal is to take a multidisciplinary approach to explore a highly sensitive and scalable malaria nucleic acid screening test on a USB interfaced device. This research objective will be achieved by carrying out the following three research tasks. Task 1, assay optimization and validation, with the goal to increase the DNA extraction yield and to increase the loop-mediated isothermal amplification assay copy number sensitivity. Task 2, device integration and instrumentation, with the goal to develop the disposable microfluidic chip and the ultracompact USB interfaced analyzer. Task 3, device performance evaluation with lab-archived blood samples collected from field sites, with the goal to determine its sensitivity, specificity, reproducibility and limits of detection. The innovation of the proposed work are three folds: (1) Highly sensitive malaria isothermal amplification assay could be performed as simple as lateral flow-based testing, (2) Scalable nucleic acid testing throughput and asynchronous processing capability provided by the cascading capability of a tier tree topology of USB hubs, and (3) Versatile platform technology that can be widely disseminated to situations that demand portability, connectivity and ease-of-use.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在过去的十年中，疟疾的控制努力增加导致全球疟疾发病率急剧下降，世界卫生组织认可了实现全球疟疾消除和消除的雄心勃勃的目标。从疟疾控制到消除疟疾的重点改变需要快速筛查疟疾的简单方法。当前的疟疾筛查测试几乎完全依赖于显微镜和免疫测试。由于检测能力有限，两种方法都可能会错过重要信息。核酸测试（NAT）当前是最敏感的方法。不幸的是，迄今为止开发的基于NAT的方法主要需要某些基础架构和熟练的技术人员。迫切需要改善疟疾筛查测试，结合了基于侧向流动测试（可扩展吞吐量，最小训练）和NAT（高度敏感和特定）的好处。拟议研究的成功将在国内和全球范围内增强医疗保健系统。作为一种平台技术，它将允许将高度敏感的测试提供给遥远，服务不足和资源有限的社区。此外，拟议的教育和推广活动将通过独特的基于实验的互动活动来促进学生的参与。该提案的研究目标是采用多学科的方法来探索在USB接口设备上进行高度敏感和可扩展的核酸筛选测试。这项研究目标将通过执行以下三项研究任务来实现。任务1，测定优化和验证，目的是增加DNA提取产率并增加循环介导的等温放大测定测定拷贝数灵敏度。任务2，设备的集成和仪器，目的是开发一次性微流体芯片和Ultraccact USB接口分析仪。任务3，设备性能评估，并通过从现场站点收集的实验室血液样本，目的是确定其敏感性，特异性，可重复性和检测限制。拟议工作的创新是三倍：（1）高度敏感的疟疾等温度放大测定可以与基于侧流的测试一样简单，（（2）可伸缩的核酸测试吞吐量和异步处理能力，由USB轮毂和（3）ausb Hubs and（3）and tier Treem tos and（3）的层次能力提供的能力，该层次的层压能力（3）。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的影响审查标准来评估的，反映了NSF的法定任务。