A commercialization-ready technology for the rapid precision diagnosis of urinary tract infections - solving scalability and reproducibility challenges

尿路感染（UTIs）是社区中最常见的感染，约2%的社区咨询与UTIs有关。今天诊断UTI和选择治疗的临床方法依赖于长时间（> 16小时）的细菌生长培养。这导致治疗延迟或在检测或确定感染原因之前经验性地施用抗生素。抗生素的延迟或无效使用会导致严重后果，如肾脏感染或尿脓毒症，而抗生素的过度使用会增加耐药性感染的发生率。现有的快速UTI测试依赖于尿试纸，不能提供治疗选择所需的种属鉴定。 迫切需要一种平台，可以在单个医生的咨询期间检测和识别致病性UTI病原体，以实现精确治疗的处方。这就需要一种可靠而简单、快速且具有成本效益的检测方法来检测和鉴定导致UTI的病原体。我们一直在开发这样的快速测试，基于电化学芯片功能化， 细菌捕获功能性DNA序列，用于检测和鉴定导致UTI的主要生物体，并且已经证明了临床上可接受的灵敏度和特异性。 在这项提案中，我们的目标是开发一种市场上现成的基于芯片的原型，该原型使用不同的功能核酸序列检测一组细菌（即多路复用），并且可以使用可扩展的丝网印刷技术制造。然后，我们将进行一项小型试点研究，以评估这种多路复用和可扩展的系统在分析临床尿液样本以检测和识别引起尿路感染的病原体方面的可行性。这项加拿大技术的市场转化预计将（1）实现以患者为中心的

Urinary tract infections (UTIs) are the most common infections treated in the community, with about 2% of all community consultations being related to UTIs. Today's clinical methods for diagnosing UTIs and selecting treatment rely on lengthy (> 16 hours) bacterial growth cultures. This results in treatment delays or the empirical administration of antibiotics before detecting or identifying the cause of the infection. The delayed or ineffective use of antibiotics leads to serious consequences such as kidney infections or urosepsis, and the excessive use of antibiotics increases the rate of antibiotic-resistant infections. The existing rapid UTI tests, relying on urine dip sticks, do not provide the species identification that is needed for treatment selection. There is an urgent unmet need for a platform that can detect and identify the causative UTI pathogens during a single doctor's consultation to enable the prescription of precision treatments. This poses the requirement for a reliable yet simple, rapid, and cost-effective test for detecting and identifying pathogens that cause UTI. We have been developing such rapid test, based on an electrochemical chip functionalized with bacterium-capturing functional DNA sequences, for detecting and identifying the leading organisms that cause UTIs, and have demonstrated clinically-acceptable sensitivity and specificity. In this proposal, we will aim at developing a market-ready chip-based prototype that detects a panel of bacteria using different functional nucleic acid sequences (i.e. is multiplexed) and can be manufactured using the scalable screen printing technology. We will then run a small pilot study to assess the feasibility of this multiplexed and scalable system in analysing clinical urine samples for detecting and identifying UTI-causing pathogens. The market translation of this Canadian technology is expected to (1) enable patient-centered