SBIR Phase I: Point-of-Care Diagnostic Tool for Identifying Extended Spectrum β-Lactamase E. Coli in Urinary Tract Infection

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力在于展示基于新技术的尿路感染患者即时诊断设备的商业可行性和临床效益。在美国，每年有1000万次泌尿道感染的初级保健就诊。这些患者中超过15%患有抗生素耐药感染。临床研究表明，准确识别和早期诊断感染菌的抗生素耐药性可缩短治疗周期，消除抗生素滥用，降低患者平均费用。然而，现场诊断测试返回有关细菌身份和抗生素耐药性的分子信息仍然是一项重大挑战。目前以实验室为基础的检测费用昂贵，周转时间长，需要熟练的技术人员和设备齐全的实验室。在大多数情况下，这导致在从测试结果返回信息之前开出经验性抗生素处方。开展快速、现场、易于实施和经常使用的抗菌素耐药性筛查对于应对抗菌素耐药性和抗生素滥用的持续威胁至关重要。该设备将适用于门诊诊所、家庭保健和住院设施。它将使细菌感染的治疗从经验性转向循证性。这项小企业创新研究（SBIR）第一阶段项目将开发一种即时护理设备，用于从未经处理的尿液样本中现场鉴定尿路感染中的大肠杆菌和相关的广谱β-内酰胺酶（ESBL）抗生素耐药基因。该装置采用新型的、正在申请专利的电化学核酸传感技术和环介导的等温扩增法来半定量地测量目标细菌基因。该装置由一个一次性微流体盒和一个便携式多功能读取器组成。自包含的微流体传感盒支持样品制备，等温扩增，和序列特异性电化学检测。这种传感技术和高度集成的样品处理微流体的新组合将使开发急需的即时诊断解决方案成为可能。该项目将展示细菌检测的特异性、识别多种基因型的能力、设备操作的便利性以及这种即时护理设备的便携性。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 lies in demonstrating the commercial viability and clinical benefit of a point-of-care diagnostics device based on novel technologies for patients with urinary tract infections. There are 10 million primary care visits for urinary tract infections per year in the United States. More than 15% of these patients suffer antibiotic-resistant infections. Clinical studies have shown that accurate identification and early diagnosis of the antibiotic resistance of the infecting bacteria shorten the treatment period, eliminate antibiotic misuse, and reduce average patient costs. However, on-site diagnostic testing that returns molecular information about the bacterial identity and antibiotic resistance remains a significant challenge. Current laboratory-based tests are costly, have long turnaround times, and require skilled technicians and well-equipped laboratories. In most cases, this results in empirical antibiotic prescriptions before the information is returned from test results. Developing rapid, on-site, easy-to-implement, and frequently used antimicrobial resistance screening is essential to combat the ongoing threat of antimicrobial resistance and antibiotic misuse. This device will be suitable for outpatient clinics, home healthcare, and inpatient facilities. It will enable a shift from empirical to evidence-based treatment of bacterial infections.This Small Business Innovation Research (SBIR) Phase I project will develop a point-of-care device for the on-site identification of E. coli and associated extended-spectrum β-lactamase (ESBL) antibiotic resistance genes in urinary tract infections from unprocessed urine samples. The device uses novel, patent-pending electrochemical nucleic acid sensing techniques and a loop-mediated isothermal amplification assay to semi-quantitatively measure target bacterial genes. The device consists of a disposable microfluidic cartridge and a portable multifunctional reader. The self-contained microfluidic sensing cartridge supports sample preparation, isothermal amplification, and sequence-specific electrochemical detection. This novel combination of sensing technology and highly integrated sample handling microfluidics will enable the development of critically needed point-of-care diagnostic solutions. The project will demonstrate the specificity of bacterial detection, the ability to identify multiple genotypes, the ease of device operation, and the portability of this point-of-care device.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.