Next Generation Tools for Onsite Monitoring and Treatment of Drug of Abuse-Dependent Persons

摘要 阿片类药物滥用障碍（OAD）每年影响210万美国人，导致药物过量， 数以万计的人死亡率飙升除了其巨大的社会影响，OAD还具有 数十亿美元的价格标签，其中包括785亿美元，专门用于医疗保健和其他相关费用， 处方阿片类药物滥用和误用。尽管存在有效的干预措施，但这些措施的利用率极低- 目前，只有不到五分之一的美国处方OUD患者接受治疗， 在处方阿片类药物管理不善所消耗的财政资源中， 使用.随着治疗计划的扩大以满足需求，他们能够提供全面的服务至关重要 以最好地支持患者康复。在OAD的潜在治疗选择中，药物辅助治疗 (MAT)阿片类药物成瘾-通常使用美沙酮，丁丙诺啡或纳洛酮-已被证明， 减少戒断症状，并与减少过量风险和改善母亲和胎儿 妊娠的结果。自从阿片类药物成瘾的药物辅助治疗（MAT）开始以来， 测试提供了治疗效果的客观测量和监测患者进展的工具， 然而，目前的方法不适合用于药物治疗环境。液相色谱-串联质谱 质谱法（LC-MS-MS）灵敏度高，但该方法产生结果的速度慢，并且需要繁琐的样品 处理.易于使用的免疫层析试纸（ICS）是金标准参考方法， 在护理点设置，但它们是非定量的，并且具有有限的多路复用能力。一种多路复用工具， 监测MAT是理想的，因为OUD患者的系统中可能有多种阿片类药物， 治疗过程包括主要成瘾性阿片类药物、治疗阿片类药物和不太理想的替代品， 成瘾性阿片类药物认识到这一未满足的需求，在成瘾治疗设置一个简单的，但 SensoDx是一种灵敏的仪器，可以测量临床标本中的多种阿片类药物， 滥用测试芯片策略，实现微流体技术，用于高灵敏度检测 阿片类药物在以前的工作（I期研究）中，我们开发并临床测试了一种三重检测靶向 口服液中丁丙诺啡、可卡因和吗啡同时定量测定 丁丙诺啡辅助治疗。此第二阶段项目将交付一组里程碑-优化的测试卡片 （精度、成本、尺寸），扩展的多路复用能力以检测七种药物（丁丙诺啡，吗啡， 羟考酮、美沙酮、海洛因、芬太尼和可卡因）和中试规模临床验证（在接受 MAT），这将为SensoDx Drug ScreenTM平台原型奠定基础并进行概念验证 用于设计和制造定稿、GLP制造和测试。这些努力将导致商业 放行分析仪仪器、取样装置和定制一次性用品，以便进入实验室， 芯片市场，价值42.3亿美元（2016年），预计到2022年复合年增长率为11%。

Abstract Opioid abuse disorder (OAD) affects 2.1 million of Americans annually resulting in overdoses numbering in the tens of thousands and skyrocketing rates of mortality. In addition to its enormous social impact, OAD carries a multi-billion-dollar price tag that includes $78.5 billion, specifically for health care and other costs related to prescription opioid abuse and misuse. Although effective interventions exist, they are highly underutilized – Currently less than 1-in-5 Americans with prescription OUDs receive treatment for their disorder, the $2.8 billion spent accounting for less than 4% of the financial resources consumed by mismanagement of prescription opioid use. As treatment programs expand to meet need, it is critical that they be able to offer comprehensive services to best support patient recovery. Among potential treatment options for OAD, medication-assisted treatment (MAT) for opioid addiction – typically employing methadone, buprenorphine or naltrexone – has been shown to reduce withdrawal symptoms and is associated with reduced overdose risk and improved maternal and fetal outcomes in pregnancy. Since the inception of medication-assisted treatment (MAT) for opioid addiction, drug testing has provided both an objective measure of treatment efficacy and a tool to monitor patient progress, however, current methods are ill-suited for use in drug treatment settings. Liquid chromatography–tandem mass spectrometry (LC–MS-MS) is highly sensitive, but the method is slow to yield results and requires tedious sample processing. Easy to use immunochromatographic test strips (ICS) are gold-standard reference methods for point-of-care settings, but they are non-quantitative and have limited multiplexing capacity. A multiplexing tool is desirable for monitoring MAT because patients with OUD may have multiple opioids in their system over the course of treatment including the primary addictive opioid, treatment opioid, and less desirable substitutes for the addictive opioid of choice. Recognizing this unmet need in addiction treatment settings for a simple, yet sensitive, instrument that can measure multiple opioids in clinical specimens, SensoDx conceptualized a drug of abuse testing-on-a-chip strategy that implements microfluidics technology for high-sensitivity detection of opioids. In previous work (Phase I studies), we developed and clinically tested a triplex assay targeting simultaneous quantitative determination of buprenorphine, cocaine and morphine in oral fluid for use in buprenorphine-assisted treatment. This Phase II project will deliver a set of milestones – an optimized cartridge (precision, cost, size), expanded multiplexing capabilities to detection of seven drugs (buprenorphine, morphine, oxycodone, methadone, heroine, fentanyl, and cocaine), and pilot-scale clinical validation (in patients undergoing MAT) that will form the foundation and proof-of-concept for a prototype SensoDx Drug ScreenTM platform ready for design and fabrication finalization, GLP manufacturing and testing. The efforts will result in the commercial release of analyzer instrumentation, sampling devices and customized disposables for entry into the Lab-on-a- Chip market, valued at $4.23 Billion (in 2016) and expected to grow at a CAGR of 11% by 2022.