SBIR Phase II: Universal electronic platform and system for rapid (direct from sample) phenotypic Antibiotic Susceptibility Testing (AST)

SBIR 第二阶段：用于快速（直接来自样本）表型抗生素敏感性测试 (AST) 的通用电子平台和系统

• 批准号: 1831243
• 负责人: Roy Swiger
• 金额: $ 72.02万
• 依托单位: Impedx Diagnostics
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2020-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1831243&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Universal; electronic

This SBIR Phase I project addresses the need to reduce the time associated with conducting tests currently used to establish targeted antibiotic (and dose) to treat infections. Sepsis and septic shock are one of the leading contributors to death in US Hospitals, responsible for 250,000 deaths annually (estimated at 30-50% of all hospital deaths). To combat these high death rates, time is of the essence. The administration of targeted (versus broad-spectrum) antibiotic therapy in the first five to six hours of septic shock increases the likelihood of survival by roughly fifty percent. This project combines electronics and microchannel fluidics to rapidly obtain results on antibiotic susceptibility. The project requires engineering, software development, and method development, resulting in an instrument that utilizes disposable cards to conduct the testing. The resulting product will allow transition from broad spectrum to targeted antibiotic therapy faster (1 day - weeks), leading to major benefits: (1) patient outcomes are greatly improved by faster transition to directed antibiotic therapy; (2) Reduced hospitalization stays (reduced intensive care stays), resulting in significant monetary saving for healthcare systems (estimated at a cost savings of at least $3.75B annually). (3) Reduced broad-spectrum antibiotic therapy reduces the current fostering of antibiotic resistance in healthcare settings globally. This project uses Microchannel Electrical Impedance Spectroscopy (m-EIS) to measure the "bulk capacitance" (Cb) of a suspension. Cb is a measure of the amount of charge transiently accumulated at the membranes of living cells in a suspension. Cell proliferation results in an increase in Cb, whereas cell death results in a decrease. Using m-EIS to measure bacteria in the presence of candidate antibiotics and doses, is robust, sensitive, and extremely fast, determining, in real time, cell growth, stasis, or death (in approximately 4 hrs). This project will develop a rapid, direct-from-sample, inexpensive commercial system. This is achieved by using commercial MNPs to isolate microorganisms from clinical samples such as blood culture broth, urine, sputum etc., and re-suspending the pathogens in specified volumes of growth media to obtain a suspension containing optimized concentrations of bacteria. Pathogen growth or death is then monitored using m-EIS in microfluidic cards where they are exposed to a range of antibiotic concentrations. The result is a phenotypic antibiotic susceptibility (AST) profile, yielding the minimal inhibitory concentration (MIC) of multiple candidate antibiotics within 4 hours of sample collection. The AST and MIC information is then used to treat infections with targeted therapeutic. The first products utilizing this system/method will focus on urine and positive blood culture broth samples.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.

该SBIR I期项目解决了减少与目前用于确定治疗感染的靶向抗生素（和剂量）的测试相关的时间的需求。 脓毒症和脓毒性休克是美国医院死亡的主要原因之一，每年造成250，000例死亡（估计占所有医院死亡的30-50%）。 为了应对这些高死亡率，时间是至关重要的。 在感染性休克的前5 - 6小时内给予靶向（相对于广谱）抗生素治疗可使存活率提高约50%。 该项目结合了电子学和微通道流体学，以快速获得抗生素敏感性的结果。 该项目需要工程、软件开发和方法开发，从而产生一种利用一次性卡进行测试的仪器。 由此产生的产品将允许更快地从广谱抗生素治疗过渡到靶向抗生素治疗（1天-周），导致主要益处：（1）通过更快地过渡到定向抗生素治疗，患者结果大大改善;（2）减少住院时间（减少重症监护住院时间），从而为医疗保健系统节省大量资金（估计每年至少节省37.5亿美元的成本）。 (3)减少广谱抗生素治疗可以减少目前全球医疗机构中抗生素耐药性的培养。该项目使用微通道电阻抗谱（m-EIS）来测量悬浮液的“体电容”（Cb）。Cb是悬浮液中活细胞膜上瞬时积累的电荷量的量度。细胞增殖导致Cb增加，而细胞死亡导致Cb减少。 使用m-EIS在候选抗生素和剂量存在下测量细菌是稳健的、灵敏的和极快的，其真实的时间确定细胞生长、停滞或死亡（在大约4小时内）。 该项目将开发一种快速、直接从样品提取、廉价的商业系统。这是通过使用商业MNP从临床样品如血培养肉汤、尿、痰等中分离微生物来实现的，和将病原体重新悬浮在特定体积的生长培养基中以获得含有优化浓度的细菌的悬浮液。 然后使用微流控卡中的m-EIS监测病原体生长或死亡，其中它们暴露于一系列抗生素浓度。结果是表型抗生素敏感性（AST）谱，在样品收集的4小时内产生多种候选抗生素的最小抑菌浓度（MIC）。AST和MIC信息然后用于用靶向治疗剂治疗感染。 利用该系统/方法的第一批产品将专注于尿液和阳性血培养肉汤样本。该奖项反映了NSF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。