SBIR Phase I :Point-of-Care Test for Identifying Gram-Negative Urinary Tract Infections in Companion Animals

SBIR 第一阶段：用于识别伴侣动物革兰氏阴性尿路感染的护理点测试

• 批准号: 1746866
• 负责人: Edgar Goluch
• 金额: $ 22.5万
• 依托单位: QSM Diagnostics INC
• 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: 2018-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1746866&HistoricalAwards=false
• 关键词: SBIR; Phase; Point; Care; Test

This SBIR Phase I project will develop a hand-held, point-of-care, sensing strip and instrument for immediate identification of which bacterial species are causing a urinary tract infection (UTI) in a companion animal. This technology will allow veterinarians to judiciously prescribe antibiotics for an animal during the initial examination. In the United States alone, there are nearly 1.5 million veterinary visits annually for UTIs in dogs and cats. The average time to initial UTI test results is 48 hours, during which time the animal is generally consuming antibiotics. Less than half of urine cultures show any bacterial growth, indicating that the majority of antibiotic prescriptions were unnecessary. Further, it is important to identify which bacterial species are causing the UTI, so that the proper antibiotic can be administered. Prudent use of antibiotics will control the spread of infection and the emergence of antibiotic resistance, thus resulting in healthier animals and reducing the need for new antibiotic drug development. This project will help translate the initial research and discoveries that were funded previously by the National Science Foundation. The underlying principle for this technology is that each bacterial species produces and excretes its own unique set of chemicals that are used to coordinate intercellular activities, analogous to pheromones produced by animals. It is possible to identify what bacterial cells are present in a sample by detecting these chemicals. There are much greater quantities of the chemicals in the sample than bacterial cells, making this approach more sensitive and easier to implement than other technologies.The proposed research will result in the creation of a label-free, aptamer-based, electrochemical sensing platform for the detection and identification of the four most common Gram-negative bacterial pathogens causing UTIs in companion animals, within two minutes of sample collection. The novelty of the approach is to measure unique quorum sensing molecules (QSMs) that are secreted by the bacteria. These QSMs are produced by all bacterial cells continuously at a rate of approximately 10,000 molecules per hour, thereby improving the limit of detection by four orders of magnitude. An array of electrodes, modified with novel aptamers and functionalized with electro-active molecules, will be used to detect the QSMs, acting as biomarkers, produced by each bacterial species. Combining optimized aptamer molecules with electrochemical sensing and a proprietary signal processing algorithm allows for unprecedented limits of detection, sensitivity, and specificity. The technology will work directly in complex fluids without any reagent addition or separation steps.

该SBIR第I阶段项目将开发一种手持式、即时护理、传感条和仪器，用于立即识别哪些细菌物种导致伴侣动物的尿路感染（UTI）。这项技术将允许兽医在初步检查期间明智地为动物开抗生素。仅在美国，每年就有近150万名兽医因狗和猫的UTI就诊。到初始UTI测试结果的平均时间是48小时，在此期间，动物通常会服用抗生素。不到一半的尿液培养显示任何细菌生长，表明大多数抗生素处方是不必要的。此外，重要的是要确定哪些细菌物种引起UTI，以便可以给予适当的抗生素。谨慎使用抗生素将控制感染的传播和抗生素耐药性的出现，从而使动物更健康，并减少对新抗生素药物开发的需求。该项目将帮助翻译先前由美国国家科学基金会资助的初步研究和发现。这项技术的基本原理是，每种细菌都会产生和分泌自己独特的一套化学物质，用于协调细胞间的活动，类似于动物产生的信息素。可以通过检测这些化学物质来识别样品中存在的细菌细胞。样品中的化学物质比细菌细胞多得多，使得这种方法比其他技术更敏感，更容易实施。拟议的研究将导致创建一个无标记的，基于适体的电化学传感平台，用于检测和鉴定四种最常见的导致伴侣动物UTI的革兰氏阴性细菌病原体，在样品采集后两分钟内。该方法的新奇在于测量细菌分泌的独特的群体感应分子（QSM）。这些QSM由所有细菌细胞以每小时约10，000个分子的速率连续产生，从而将检测限提高了四个数量级。用新型适体修饰并用电活性分子功能化的电极阵列将用于检测每种细菌产生的QSM，其作为生物标志物。将优化的适体分子与电化学传感和专有的信号处理算法相结合，可以实现前所未有的检测、灵敏度和特异性限制。该技术将直接在复杂流体中工作，无需任何试剂添加或分离步骤。