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，导致美国 数以万计的死亡率和飞涨的死亡率。除了其巨大的社会影响外，OAD还具有 数十亿美元的价格标签，其中包括785亿美元，特别是医疗保健和其他与 处方类阿片类药物滥用和误用。尽管存在有效的干预措施，但它们的利用严重不足-- 目前，只有不到五分之一的服用处方药的美国人接受了这种疾病的治疗，这一费用为28亿美元 花费不到处方阿片类药物管理不善所消耗的财政资源的4% 使用。随着治疗方案的扩展以满足需求，关键是它们能够提供全面的服务 以最好地支持病人的康复。在OAD的潜在治疗方案中，药物辅助治疗 阿片成瘾(MAT)--通常使用美沙酮、丁丙诺啡或纳曲酮--已被证明 减少戒断症状，并与降低过量用药风险和改善母婴状况有关 妊娠结局。自从药物辅助治疗(MAT)开始治疗阿片成瘾以来，药物 检测既提供了治疗效果的客观衡量，也提供了监测患者进展的工具， 然而，目前的方法不适合在药物治疗环境中使用。液-质联用法 光谱分析(LC-MS-MS)灵敏度高，但分析速度慢，样品繁琐 正在处理。易于使用的免疫层析试纸(ICS)是检测 护理点设置，但它们是非定量的，并且多路复用能力有限。一种多路复用工具是 最好用于监测MAT，因为OUD患者的系统中可能有多个阿片类药物 疗程包括主要成瘾阿片类药物、治疗类阿片类药物和不太可取的替代药物 令人上瘾的阿片类药物。在成瘾治疗环境中认识到这种未得到满足的需求是一种简单而又 一种灵敏的仪器，可以测量临床标本中的多种阿片类药物，SensoDx概念化了一种药物 实施微流控技术的芯片上滥用检测战略，用于高灵敏度检测 阿片类药物。在以前的工作中(第一阶段研究)，我们开发并临床测试了一种三联体靶向试验 丁丙诺啡、可卡因、吗啡口服液中丁丙诺啡、可卡因、吗啡的同时测定 丁丙诺啡辅助治疗。该第二阶段项目将提供一系列里程碑--优化的墨盒 (精密度、成本、大小)，扩展了多路复用能力，可检测七种药物(丁丙诺啡、吗啡、 羟考酮、美沙酮、海洛因、芬太尼和可卡因)，以及中试规模的临床验证(在接受 Mat)，这将为SensoDx Drug ScreenTM平台的原型奠定基础并进行概念验证 负责设计和制造定型、GLP制造和测试。这些努力将导致商业 发放分析仪仪器、采样设备和定制一次性用品，以便进入a-a-a实验室- 芯片市场，价值42.3亿美元(2016年)，预计到2022年以11%的复合年增长率增长。

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.