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，如果不采取行动阻止这一全球威胁，预计到2050年，这一数字将上升到每年1000万人死亡。抗生素的过度使用和抗生素的处方对细菌不敏感，导致抗生素耐药性的上升。AMR是一个紧迫而复杂的问题，在加拿大和世界范围内构成重大的健康和经济威胁。金标准抗生素敏感性测试（AST）测定是时间（2- 3天）和劳动密集型的，适合于集中实验室设施。我们聚集了麦吉尔大学、MUHC和尼康加拿大公司的专家团队。开发一种便携式和具有成本效益的测试平台，用于快速表型抗生素敏感性测试（AST），该测试平台具有广泛的致病菌的通用功能，并可在需要时（如偏远地区和低资源地区）直接测试人体样本。所提出的诊断平台是基于一种新型的等离子体纳米结构，该纳米结构在刃天青转化为试卤灵的过程中提供了超灵敏的光学读数-这是抗生素暴露期间细菌活力和生长的指标。在这里，我们建议将我们的新型比色纳米结构与用于在不到1小时内进行便携式多重AST的微流体样品递送相结合。在尼康的支持下（实物捐助），我们将开发一种便携式和小型化的成像盒，能够容纳用于实时成像和数据采集的微流控盒。最后，我们将在样本处理的不同阶段，在疑似菌血症患者的临床样本中测试该平台，并将结果与标准AST进行比较，以进行微生物鉴定和药敏试验。拟议的方法将AST的周转时间缩短到不到1小时，提高了我们开发低成本诊断方法（每次测试5美元）的知识，产生创新并确保商业化，为加拿大经济注入活力。减少诊断结果的时间和低成本的潜力对加拿大卫生系统有重大的经济影响。

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.