SBIR Phase II: Integrated Point-of-Care System for Rapid Pathogen Identification and Characterization

这项小企业创新研究（SBIR）第二阶段项目的更广泛影响/商业潜力是，在妇女健康等尚未得到满足的重大临床需求领域，改善了获得最先进分子诊断技术的机会。在美国国家科学基金会I-Corps项目期间，由于目前临床工作流程冗长，临床需求显著未满足，疾病发病率高，研究小组确定尿路感染（uti）是一个紧迫的问题。尿路感染是美国妇女就医的最常见原因之一，也是该国抗生素处方的最大来源之一。未经治疗的尿路感染可导致严重的并发症，包括全身细菌感染，如菌血症。尽管尿路感染的严重性和普遍性，但诊断方法仍然非常耗时，并且依赖于过时的、基于培养的病原体检测方法。这种耗时的诊断工作流程通常会让女性忍受长达三天的痛苦，然后才会给她们开适当的抗生素治疗。由于当前医疗保健工作流程存在缺陷，获得医疗服务的机会有限的妇女需要等待较长的结果等待时间，而且往往从未得到适当的治疗。这个小企业创新研究（SBIR）二期项目利用一种新型纳米传感器嵌入到集成诊断耗材中，用于直接从患者样本中快速检测目标核酸序列。消耗品与专有的台式读出仪器相连接，用于在护理点进行测试分析和结果报告。该技术通过超灵敏的光学检测方式消除了细菌培养和核酸扩增的需要，在几分钟内提供物种水平的信息和基因型抗生素耐药性数据。所提出的平台的应用超越了尿路感染，可以应用于目前使用冗长的基于培养或基于放大的诊断工作流程的其他临床场景，例如性传播感染和呼吸道感染。成功的产品商业化将需要满足临床可操作的时间尺度和分析性能基准。重要的是为医护人员开发一个简单的集成工作流程，以便在护理点实现单步操作。第二阶段的技术目标集中在纳米传感器的开发和中试规模制造，灵敏度的优化和数据分析方法的鲁棒性，以告知阅读器光学硬件的下选择，以及系统集成和用户测试。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is improved access to state-of-the-art molecular diagnostic technologies in areas of significant unmet clinical need, such as women’s health. During the NSF I-Corps Program, the team identified urinary tract infections (UTIs) as pressing problem due to the currently lengthy clinical workflows, significant unmet clinical need, and large disease incidence. UTIs are one the most common causes of a healthcare visit for women in the United States and represent one of largest sources of antibiotic prescriptions in the country. Untreated UTIs can lead to severe complications for the patient, including systemic bacterial infections such as bacteremia. Despite the severity and prevalence of UTIs, diagnostic methodologies remain extremely time-consuming and rely on antiquated, culture-based methodologies for pathogen detection. This time-intensive diagnostic workflow typically leaves women in pain for up to three days before they are prescribed the appropriate antibiotic therapy. As a result of shortcomings in current healthcare workflows, women who have limited access to care are subject to longer result wait times, and often never receive the appropriate treatment. This Small Business Innovation Research (SBIR) Phase II project utilizes a novel nanosensor embedded into an integrated diagnostic consumable for rapid detection of target nucleic acid sequences directly from patient samples. The consumable is coupled to a proprietary bench-top readout instrument for test analysis and result reporting at the point-of-care. The technology eliminates the need for bacterial culture and nucleic acid amplification through an ultrasensitive optical detection modality, providing species-level information and genotypic antibiotic resistance data within minutes. Applications of the proposed platform translate beyond UTIs to other clinical scenarios that currently employ lengthy culture-based or amplification-based diagnostic workflows, such as sexually transmitted infections and respiratory infections. Successful product commercialization will require meeting clinically actionable timescales and assay performance benchmarks. Of importance is the development of a simple, integrated workflow for healthcare workers to enable single-step operation at the point-of-care. The Phase II technical objectives focus on the development and pilot-scale fabrication of the nanosensor, the optimization of sensitivity and robustness of data analysis methodologies to inform down-selection of reader optical hardware, and system integration and user testing.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.