SBIR Phase II: Rapid Assessment of Antibiotic Resistance by Mass Measurement

这个小企业创新研究第一阶段项目建议开发一种“近距离护理”仪器，可以在不到一小时的时间内评估引起感染的细菌的抗生素敏感性。mems制造的传感器和集成流体将以接近1飞图的分辨率测量少量体外细菌的质量和生长速率。通过将细菌暴露在一组抗生素中，同时监测其生长速度，可以非常迅速地确定感染的易感性概况。利用这些信息，医生将能够比使用传统方法更快地选择有针对性的抗生素治疗，传统方法需要孵育并需要24小时或更长时间——这是节省时间的关键。该平台将在生理盐水和健康尿液基质中对具有一定敏感性的多种大肠杆菌菌株进行验证。为了证明临床价值，结果将与常规方法进行比较。将对引起尿路感染的大肠杆菌和肺炎克雷伯菌临床分离株以及耐甲氧西林金黄色葡萄球菌（MRSA）进行进一步检测。这个项目更广泛的影响/商业潜力将是改善感染的医疗结果和促进抗生素管理。耐药细菌的迅速蔓延，加上新抗生素发现的减少，构成了当今最严重的健康威胁之一。在美国，每年有超过10万人死于感染，仅次于癌症和心脏病。传染病专家一致认为，快速诊断以确定耐药性对于实施有针对性的抗生素治疗、产生更好的结果以及最大限度地减少耐药菌株的传播至关重要。这里要开发的测试直接解决了这些需求。该项目的目标是导致大多数医院获得性感染的尿路感染；以及MRSA（耐甲氧西林金黄色葡萄球菌），每年导致超过2万美国人死亡。该平台将被配置为在大多数医院的微生物实验室中“近距离护理”使用，并在美国5亿美元的药敏测试设备和试剂市场中占据很大一部分。该平台还将解决抗生素发现和实验室研究的短期市场。

This Small Business Innovation Research Phase I project proposes to develop a "close-to-care" instrument that can assess antibiotic susceptibility of infection-causing bacteria in less than one hour. MEMS-fabricated sensors and integrated fluidics will measure the mass and growth rate of a small number of bacteria in-vitro with a resolution near 1 femtogram. By exposing the bacteria to a panel of antibiotics while monitoring growth rate, an infection's susceptibility profile will be determined very rapidly. Using this information, doctors will be able to select targeted antibiotic treatment much faster than is possible using conventional methods that require incubation and take 24 hours or longer - a crucial time savings. The platform will be validated on multiple E. coli strains that have a range of susceptibility, in both saline and healthy urine matrices. To demonstrate clinical value, the results will be compared to conventional methods. Additional tests will be performed on clinical isolates of E. coli and K. pneumoniae that cause urinary tract infections, and on MRSA (methicillin-resistant Staphylococcus aureus).The broader impact/commercial potential of this project will be to improve medical outcomes of infection and to facilitate antibiotic stewardship. The rapidly expanding prevalence of resistant bacteria, combined with a decline in the discovery of new antibiotics, pose one of today's most dire health threats. More than 100,000 people die of infections each year in the U.S., behind only cancer and heart disease. There is unanimous consensus among infectious disease experts that rapid diagnostics to identify resistance are crucial for administering targeted antibiotic therapy, leading to better outcomes, and for minimizing the spread of resistant strains. The test to be developed here directly addresses these needs. The project targets UTI (urinary tract infections) that are responsible for the majority of hospital-acquired infections; and MRSA (methicillin-resistant Staphylococcus aureus) that kills more than 20,000 Americans every year. The platform will be configured for "close-to-care" use in microbiology labs found in most hospitals, and capture a significant fraction of the $500M U.S. market for susceptibility testing equipment and reagents. The platform also will address nearer-term markets in antibiotic discovery and laboratory research.