Development of a miniaturized imaging system for antimicrobial resistance profiling at the point of need

抗菌素耐药性(AMR)是全球十大公共卫生威胁之一，每年造成70万人死亡，如果不采取行动遏制这一全球威胁，预计到2050年，这一数字将上升到每年1000万人。抗生素的过度使用和细菌不敏感的抗生素处方导致了抗生素耐药性的上升。AMR是一个紧迫而复杂的问题，在加拿大国内和世界范围内都构成了重大的健康和经济威胁。抗生素敏感性试验(AST)的金标准是时间(2-3天)和劳动强度大，适合集中式实验室设施。我们聚集了麦吉尔大学、MUHC和尼康加拿大公司的专家团队，为快速表型抗生素敏感性测试(AST)开发了一个便携且经济高效的测试平台，该平台具有广泛的致病菌功能，并可以在需要的地方(如偏远地区和低资源地区)直接检测人体样本。拟议的诊断平台基于一种新型的等离子体纳米结构，该结构在Resazurin到Resufin的转化过程中提供了超灵敏的光学读数--Resazurin是细菌在抗生素暴露期间生存和生长的指示器。在这里，我们建议将我们的新型比色纳米结构与微流控样品传输相结合，在不到1小时的时间内实现便携式多重AST。在尼康(实物捐助)的支持下，我们将开发一种便携式和微型化的成像盒，能够容纳微流控墨盒，用于实时成像和数据采集。最后，我们将在疑似菌血症患者的临床标本中对该平台进行不同阶段的样品处理，并将结果与标准AST进行微生物鉴定和药敏试验。建议的方法将AST的周转时间减少到不到1小时，提高了我们开发低成本诊断方法的知识(每次测试5美元)，产生创新并确保商业化，为加拿大经济注入活力。以低成本缩短诊断结果所需时间的潜力对加拿大卫生系统具有重大的经济影响。

Antimicrobial Resistance (AMR) is one of the top ten global public health threats and responsible for 700,000 deaths annually, a figure that is projected to rise to 10 million deaths per year by 2050 if no action is taken to halt this global threat. The overuse of antibiotics and the prescription of antibiotics to which bacteria are not susceptible, contribute to the rise of antibiotic resistance. AMR is an urgent and complex problem that poses major health and economic threats, both within Canada and worldwide. The gold standard antibiotic susceptibility testing (AST) assays are time (2- 3 days) and labor intensive suited for centralized lab facilities. We gather a team of experts at McGill University, MUHC and Nikon Canada Inc. to develop a portable and cost-effective testing platform for rapid phenotypic antibiotic susceptibility testing (AST) with versatile functionality for a broad range of pathogenic bacteria and the possibility for direct testing of human samples at the point of need such as remote locations and low resource areas. The proposed diagnostic platform is based on a novel plasmonic nanostructure that provides an ultrasensitive optical readout during the conversion of resazurin to resorufin- an indicator for bacterial viability and growth during antibiotic exposure. Here, we propose to integrate our novel colorimetric nanostructures with a microfluidic sample delivery for portable multiplex AST in less than 1 hour. With the support of Nikon (in-kind contribution), we will develop a portable and miniaturized imaging box capable of holding the microfluidic cartridge for real-time imaging and data acquisition. Finally, we will test the platform in clinical specimens from patients with suspected bacteremia at different stages of sample processing and compare the results with standard AST for microbial identification and susceptibility testing. The proposed approach reduces the turnaround time of the AST to less than 1 hour, advances our knowledge of developing low-cost diagnostic methods ($5 per test), generate innovations and secure commercialization that energize Canadian economy. The potential to reduce the time-to-result of diagnostics a low-cost has significant economic impact on the Canadian health system.