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

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力是改善在重大未满足的临床需求领域（如妇女健康）获得最先进的分子诊断技术的机会。在NSF I-Corps计划期间，该团队将尿路感染（UTI）确定为紧迫的问题，因为目前临床工作流程冗长，临床需求严重未满足，疾病发病率高。UTI是美国女性医疗保健访问的最常见原因之一，也是该国抗生素处方的最大来源之一。未经治疗的UTI可导致患者的严重并发症，包括全身性细菌感染，如菌血症。尽管尿路感染的严重性和流行性，诊断方法仍然非常耗时，并依赖于过时的，基于培养的病原体检测方法。这种时间密集型的诊断工作流程通常会让女性在接受适当的抗生素治疗之前疼痛长达三天。 由于目前的医疗保健工作流程存在缺陷，获得护理的机会有限的妇女需要等待更长的结果，而且往往从未得到适当的治疗。该小型企业创新研究（SBIR）第二阶段项目利用嵌入集成诊断耗材的新型纳米传感器，直接从患者样本中快速检测靶核酸序列。耗材与专有的台式读出仪器连接，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模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UTI，应用于目前采用冗长的基于培养或基于扩增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行的时间表和检测性能基准。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的制造，灵敏度和数据分析方法的鲁棒性的优化，以通知向下选择的阅读器光学硬件，系统集成和用户测试。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.