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

小型企业创新研究(SBIR)第二阶段项目的更广泛影响/商业潜力是，在妇女健康等重大未得到满足的临床需求领域，更容易获得最先进的分子诊断技术。在NSF I-Corps计划期间，研究小组确定尿路感染(UTI)是迫在眉睫的问题，这是由于目前漫长的临床工作流程、重大的未得到满足的临床需求和较大的疾病发病率。尿路感染是美国女性就诊的最常见原因之一，也是美国抗生素处方的最大来源之一。未经治疗的尿路感染可能会导致患者的严重并发症，包括全身细菌感染，如菌血症。尽管尿路感染的严重性和流行率很高，但诊断方法仍然非常耗时，并依赖过时的、以培养为基础的方法进行病原体检测。这种耗时的诊断工作流程通常会让女性在被开出适当的抗生素治疗之前痛苦长达三天。由于目前医疗工作流程的缺陷，获得护理的机会有限的妇女等待结果的时间更长，而且往往得不到适当的治疗。这个小型企业创新研究(SBIR)第二阶段项目利用嵌入到集成诊断消耗品中的新型纳米传感器，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数仪器相连，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对细菌培养和核酸放大的需要，在几分钟内提供了物种级别的信息和抗生素耐药性的基因型别数据。拟议平台的应用超越了尿路感染，适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方案，例如性传播感染和呼吸道感染。成功的产品商业化将需要达到临床可操作的时间尺度和检测性能基准。重要的是为医护人员开发一个简单、集成的工作流程，以便在护理点实现单步操作。第二阶段的技术目标集中于纳米传感器的开发和中试制造，优化数据分析方法的灵敏度和稳健性，以向下选择读取器光学硬件，以及系统集成和用户测试。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.