Ultrasensitive, rapid, cost-effective, user-friendly test for respiratory viruses

描述（由申请人提供）：我们建议开发一种新的测试平台，用于对病毒感染进行快速，超灵敏，准确，用户友好且具有成本效益的即时呼吸道诊断。病毒性呼吸道感染每年导致数十万人死亡，数百万人患病，对儿童、老年人和免疫功能低下的患者尤为严重。快速和准确的呼吸道疾病诊断改善了治疗，大大减少了不适当的抗生素使用，并最大限度地减少了不必要的探索性检测的成本。目前呼吸道感染的诊断方法包括培养，需要几天时间；快速免疫测定，可能不敏感；直接荧光免疫测定，需要技术专长；还有核酸扩增，这既昂贵又复杂。许多中小型医院缺乏最敏感的病毒诊断资源，因此无法快速诊断呼吸道病毒感染患者。我们的目标是基于我们的专有技术开发一种快速灵敏的呼吸道病毒检测方法，该技术使用低成本的非放大数字成像系统，对带有荧光颗粒标记的目标分子进行计数。该系统不需要专门的培训，也不需要对样品进行预处理。这项可行性研究的具体目标是：(1)证明该技术能够快速（在5分钟内）检测呼吸道样本中的病毒抗原，灵敏度比目前的快速检测高约1000倍；(2)开发一种廉价的原型消耗品，与非处方妊娠试纸一样易于使用，并证明了一组呼吸标志物测试的可行性；(3)研制简单、低成本的原型成像仪器；(4)使用受感染的呼吸道样本，通过将两种方法的结果与以核酸检测为金标准获得的结果进行比较，证明与商业化快速方法相比，新方法的性能有所提高。为实现这些目标，应该有理由开展第二阶段项目，该项目将侧重于开发消耗品和仪器的商业化前原型，并增加检测范围，包括一组最重要的医学呼吸道病毒和其他类型呼吸道疾病（如过敏和细菌感染）的指标。这种独特的护理点平台的商业影响超出了社区医院、诊所和医生办公室的临床呼吸面板的巨大潜在市场。该平台还具有解决临床医学、工业微生物学和环境微生物学中其他重大未满足需求的潜力。公共卫生相关性：商业化的即时检测系统将对病毒性呼吸道疾病的诊断和治疗产生重大影响，病毒性呼吸道疾病是美国疾病的主要来源，估计每年有15亿呼吸道感染导致数十万人死亡。这种新的检测方法将首次使社区医院、诊所和医生办公室能够超灵敏、准确和具有成本效益地诊断呼吸道疾病。如今，这些场所的卫生保健工作者通常将样本送到参考实验室，从而无法获得早期结果。通过快速提供现场结果，这里提出的测试系统有可能加快适当治疗的交付，消除不必要的侵入性测试，缩短住院时间，并改善患者的预后。

DESCRIPTION (provided by applicant): We propose to develop a novel testing platform for enabling rapid, ultrasensitive, accurate, user-friendly, and cost-effective point-of-care respiratory diagnostics for viral infections. Viral respiratory infections result in hundreds of thousands of deaths and millions of illnesses each year and are especially serious in children, the elderly, and the immunocompromised patients. Rapid and accurate diagnosis of respiratory disease improves treatment, substantially lowers inappropriate antibiotic use, and minimizes costs from unnecessary exploratory testing. Current diagnostic methods for respiratory infections include culture, which takes days; rapid immunoassays, which can be insensitive; direct fluorescent immunoassays, which require technical expertise; and nucleic acid amplification, which is expensive and complex. Many small and medium sized hospitals lack the resources for the most sensitive viral diagnostics and therefore the ability to quickly diagnose patients for respiratory virus infections. We aim to develop a rapid and sensitive test for a panel of respiratory viruses based on our proprietary technology which uses a low-cost non-magnified digital imaging system that counts target molecules tagged with fluorescent particles. The system will require no specialized training and no pre- processing of samples. The Specific Aims of this feasibility study are to (1) demonstrate the technology's ability to rapidly (within 5 minutes) detect viral antigens in respiratory samples about 1000-fold more sensitively than current rapid tests; (2) develop an inexpensive prototype consumable that is as easy to use as an over-the- counter pregnancy test and that demonstrates the feasibility of testing for a panel of respiratory markers; (3) develop a simple low-cost prototype imaging instrument; and (4) using infected respiratory samples, demonstrate improved performance of the new assay compared to commercialized rapid methods by comparing the results of both methods to the results obtained using nucleic acid tests as the gold standard. Achieving these Aims should justify a Phase 2 project that will focus on developing pre-commercial prototypes of the consumable and instrument and increasing the range of the assay to include a panel of the most medically important respiratory viruses and indicators of other types of respiratory illness such as allergies and bacterial infection. The commercial impact of this unique point of care platform ranges beyond the large potential market for the clinical respiratory panel in community hospitals, clinics, and physicians' offices. The platform also has the potential to address other significant unmet needs in clinical medicine, industrial microbiology, and environmental microbiology. PUBLIC HEALTH RELEVANCE: The commercialized point-of-care testing system will have a substantial impact on the diagnosis and treatment of viral respiratory disease, which is a major source of illness in the United States with an estimated 1.5 billion respiratory infections causing hundreds of thousands of deaths every year. The new test will enable, for the first time, ultrasensitive, accurate, and cost-effective diagnosis of respiratory disease in community hospitals, clinics, and physicians' offices. Today, healthcare workers in these venues generally send samples to reference laboratories, precluding the ability to get early results. By delivering on-site results quickly, the test system proposed here has the potential to speed up delivery of the appropriate therapy, eliminate unnecessary and invasive testing, shorten hospital stays, and improve patient outcomes.