SBIR Phase I: Integrated Point-of-Care System for Rapid Pathogen Identification in Urinary Tract Infections

这项小企业创新研究（SBIR）第一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。由于临床工作流程长，发病率高，尿路感染是一个亟待解决的问题。在美国，尿路感染是女性寻求医疗保健的最常见诱因之一，也是抗生素处方的主要驱动因素。未经治疗的尿路感染可导致严重的并发症，如全身细菌感染。尽管尿路感染的严重程度和流行程度，但诊断方法仍然非常耗时，并且依赖于过时的基于培养的检测，这使得妇女在得到适当的抗生素治疗之前长达三天的痛苦。拟议的项目将加速尿路感染的诊断，也可用于其他感染。这个小企业创新研究（SBIR）一期项目将细胞富集的微流体方法与一种新型纳米结构底物结合起来，用于靶核酸序列的超灵敏检测。阅读器包含软件和光学硬件来检测和分析在护理点的测试结果。该技术通过超灵敏的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。该平台的应用超越了尿路感染，并在目前采用冗长的基于培养的步骤和分子测试工作流程的其他临床场景中具有实用性，例如呼吸道感染，血液感染和假体关节感染。该项目的目标是通过微流体优化和自动化来提高样品吞吐量，并通过新颖的传感器几何设计来提高灵敏度。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 I project is improved access to state-of-the-art molecular diagnostic technologies in areas of significant unmet clinical need, such as women’s health. Urinary tract infections (UTIs) are a pressing problem due to the lengthy clinical workflows and large disease incidence. UTIs are one the most common prompts for women to seek health care in the United States and represent a major driver of antibiotic prescriptions. Untreated UTIs can lead to severe complications for the patient, such as systemic bacterial infections. Despite the severity and prevalence of UTIs, diagnostic methodologies remain extremely time-consuming and rely on antiquated culture-based detection, leaving women in pain for up to three days before they are prescribed the appropriate antibiotic therapy. The proposed project will accelerate UTI diagnosis and can be used for other infections as well. This Small Business Innovation Research (SBIR) Phase I project integrates microfluidic methods for cell enrichment with a novel nanostructured substrate for ultrasensitive detection of target nucleic acid sequences. The reader contains software and optical hardware to detect and analyze the test result at the point-of-care. This technology eliminates the need for bacterial culture and nucleic acid amplification through an ultrasensitive detection modality, providing species-level information and genotypic antibiotic resistance data within minutes. The applications of this proposed platform translate beyond UTIs and have utility in other clinical scenarios that currently employ lengthy culture-based steps and molecular testing workflows, such as respiratory infections, bloodstream infections, and prosthetic joint infections. The project goal is to increase sample throughput through microfluidics optimization and automation and to improve sensitivity through novel sensor geometry design.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.