Microfluidic immunoassay as a polysubstance oral fluid screening tool for law enforcement to rapidly identify recent drug use in traffic stops to reduce traffic fatalities and injuries.

摘要 越来越多的美国人在药物的影响下驾驶（DUID）比以往任何时候都多，导致致命的运动增加。 车辆事故。每年有超过1200万司机DUID，只有一小部分执法人员（8%） 识别路边交通站中药物损害所需的高级培训，代表约220名驾驶员DUID 每一个受过高级训练的巡警就像酒精呼气测醉器，推定药物筛选技术 可以帮助巡警对DUID逮捕做出标准化和客观的决定。然而，目前的药物筛选 测试主要基于免疫层析测试条，因此，仅产生定性结果， 诊断性能，并提供有限的药物测试菜单，缺少高优先级的药物，如芬太尼。有一个 对具有实验室测试等性能特征的药物筛选技术的需求未得到满足， 包括芬太尼在内的多种高优先级药物为了实现这一目标，便携式诊断系统正在开发下一个- 新一代基于微流体的药物筛选工具，称为Integrity-1分析系统。Integrity-1分析系统 以高准确度和精确度检测小体积（<20微升）口腔液中的低丰度靶标， 传感器上的流体的新颖微流体循环。当完全开发后，该系统将具有一流的功能， 便携性、无与伦比的多路复用能力，用于更全面的药物筛选，以及分析特性 更接近于实验室仪器。我们第一阶段计划的主要目标是建立以下可行性： 用于药物筛选应用的Integrity-1分析系统。首先，我们将发展禁毒基础设施， 测试，其中包括制造测试盒和阅读器原型，以完成该项目的目标。然后我们将 开发对DUID执法高度感兴趣的多种药物和/或药物代谢物的多重测定，以及 临床毒理学应用，包括芬太尼。这项工作将最终在一个横截面的诊断准确性研究 100例受试者，来自吸毒流行率高的人群。分析将比较诊断性能 Integrity-1相对于市售口腔液ICS检测的灵敏度和特异性，通过LC-MS验证为 参考方法。这项研究的结果将推动我们的技术朝着开发初始产品的目标前进 根据FDA监管裁量权进行执法，并针对未来受监管（510[k]许可）的IVD产品， 临床毒理学及相关应用。我们的技术，当用于DUID执法时，可以帮助防止 与机动车有关的伤害和死亡，这与CDC保护美国的高级别战略目标是一致的 免受健康、安全和安保威胁。虽然并非所有人DUID都有物质使用障碍（SUD），但增加了 DUID定罪的收益也可能导致通过成瘾治疗对有SUD风险的个人进行早期干预 在毒品法庭系统里此外，这项技术所提供的近实时数据可以作为监视系统， 监测有关DUID人口发病率和所遇到的药物类型/类别的国家趋势。

Abstract More Americans are driving under the influence of drugs (DUID) than ever before, leading to an increase in fatal motor vehicle accidents. With more than 12 million drivers DUID each year, only a fraction of law enforcement officers (8%) has the advanced training needed to recognize drug impairment in roadside traffic stops, representing about 220 drivers DUID for every patrol officer with advanced training. Like the breathalyzer for alcohol, presumptive drug screening technology can aid patrol officers in making standardized and objective decisions for DUID arrest. However, current drug screening tests are primarily based on immunochromatographic test strips, and, as a result, yield merely qualitative results with poor diagnostic performance and offer limited drug test menus that are missing high-priority drugs like fentanyl. There is an unmet need for drug screening technology with performance characteristics like laboratory tests and the ability to measure multiple high-priority drugs, including fentanyl. Toward this goal, Portable Diagnostic Systems is developing a next- generation microfluidics-based drug screening tool called the Integrity-1 Analysis System. The Integrity-1 Analysis System detects low abundance targets in small volumes (<20 𝜇L) of oral fluid with high accuracy and precision, made possible by the novel microfluidic circulation of fluids over the sensors. When fully developed, the system will feature best-in-class portability, unparalleled multiplexing capability for more comprehensive drug screening, and analytical characteristics closer to laboratory-based instrumentation. Our primary objective for this Phase I program is to establish the feasibility of the Integrity-1 Analysis System for use in drug screening applications. First, we will develop the infrastructure for drug testing, which involves fabricating test cartridges and reader prototypes to complete the project’s Aims. We will then develop a multiplexed assay of multiple drugs and/or drug metabolites of high interest to DUID enforcement as well as clinical toxicology applications, including fentanyl. This work will culminate in a cross-sectional diagnostic accuracy study of 100 subjects from a population with a high prevalence of drug use. The analysis will compare the diagnostic performance (sensitivity and specificity) of the Integrity-1 relative to a commercially available oral fluid ICS test, verified by LC-MS as the reference method. The results of this study will advance our technology toward the goal of developing an initial product for law enforcement under FDA regulatory discretion, and towards future regulated (510[k] clearance) IVD products in clinical toxicology and related applications. Our technology, when adopted for DUID enforcement, could help prevent motor vehicle-related injuries and fatalities, which is consistent with CDC’s high-level strategic goals to protect America from health, safety, and security threats. While not all persons DUID have substance use disorders (SUD), increasing the yield of DUID convictions could also lead to earlier intervention for individuals at risk of SUD through addiction treatment in the drug court system. In addition, near real-time data, facilitated by this technology, could act as surveillance systems to monitor national trends regarding the population incidence rate of DUID and the types/classes of drugs encountered.