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，以实现对病毒感染的快速、超灵敏、准确、用户友好和成本效益的护理点呼吸道诊断。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。呼吸道疾病的快速和准确诊断改进了治疗，大大降低了不适当的抗生素使用，并将不必要的探索性测试的成本降至最低。目前对呼吸道感染的诊断方法包括培养，需要几天时间；快速免疫分析，可能不敏感；直接荧光免疫分析，需要专业技术；以及核酸放大，昂贵而复杂。许多中小型医院缺乏用于最敏感的病毒诊断的资源，因此缺乏快速诊断患者呼吸道病毒感染的能力。我们的目标是基于我们的专利技术开发一种快速而灵敏的呼吸道病毒检测方法，该技术使用一种低成本的非放大数字成像系统，对标记有荧光颗粒的目标分子进行计数。该系统将不需要专门的培训，也不需要对样品进行前处理。这项可行性研究的具体目的是(1)展示该技术快速(在5分钟内)检测呼吸道样本中病毒抗原的能力，其灵敏度约为目前快速测试的1000倍；(2)开发一种廉价的原型消耗品，它像非处方怀孕测试一样易于使用，并证明对一组呼吸标志物进行测试的可行性；(3)开发一种简单、低成本的成像仪器原型；以及(4)使用受感染的呼吸道样本，通过将这两种方法的结果与以核酸测试为金标准的结果进行比较，证明新的检测方法比商业化的快速方法的性能有所改善。实现这些目标应该证明第二阶段项目是合理的，该项目将侧重于开发消耗品和仪器的商业化前原型，并扩大检测范围，以包括一组最具医学意义的呼吸道病毒和其他类型的呼吸道疾病的指标，如过敏和细菌感染。这一独特的医疗点平台的商业影响超出了社区医院、诊所和医生办公室临床呼吸面板的巨大潜在市场。该平台还有可能解决临床医学、工业微生物学和环境微生物学领域其他未得到满足的重大需求。公共卫生相关性：商业化的护理点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的主要疾病来源，据估计，每年有15亿例呼吸道感染导致数十万人死亡。这项新测试将首次在社区医院、诊所和医生办公室实现对呼吸系统疾病的超灵敏、准确和成本效益高的诊断。如今，这些场馆的医护人员通常将样本送到参考实验室，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，消除不必要的和侵入性测试，缩短住院时间，并改善患者结果。

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.