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型检测平台，用于实现快速、超灵敏、准确、用户友好和具有成本效益的病毒感染即时呼吸诊断。病毒性呼吸道感染每年导致数十万人死亡和数百万人患病，在儿童、老年人和免疫功能低下的患者中尤为严重。呼吸道疾病的快速准确诊断可以改善治疗，大大降低抗生素的不当使用，并最大限度地减少不必要的探索性测试的成本。目前呼吸道感染的诊断方法包括培养，这需要几天时间;快速免疫测定，这可能是不敏感的;直接荧光免疫测定，这需要技术专长;和核酸扩增，这是昂贵和复杂的。许多中小型医院缺乏最敏感的病毒诊断资源，因此无法快速诊断患者的呼吸道病毒感染。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.本可行性研究的具体目的是（1）证明该技术快速（5分钟内）检测呼吸道样本中的病毒抗原，比目前的快速检测灵敏1000倍;（2）开发一种廉价的原型消费品，与非处方妊娠检测试剂盒一样易于使用，并证明检测一组呼吸道标志物的可行性;（3）开发一种简单的低成本原型成像仪器;（4）使用感染的呼吸道样本，通过将两种方法的结果与使用核酸检测作为金标准获得的结果进行比较，证明与商业化的快速方法相比，新检测方法的性能有所改善。实现这些目标应证明第2阶段项目的合理性，该项目将侧重于开发耗材和仪器的商业前原型，并增加检测范围，以包括一组医学上最重要的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。这种独特的床旁平台的商业影响范围超出了社区医院、诊所和医生办公室的临床呼吸系统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，这是美国的主要疾病来源，估计每年有15亿例呼吸道感染导致数十万人死亡。新的测试将首次在社区医院，诊所和医生办公室对呼吸系统疾病进行超灵敏，准确和具有成本效益的诊断。今天，这些场所的医护人员通常会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，本文提出的测试系统有可能加快提供适当的治疗，消除不必要的和侵入性的测试，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.