Sensitive and Portable Physician Office-Based Urine Analyzer to Tackle Prescription Drug Abuse

项目摘要 美国正处于处方阿片类药物的流行之中。滥用造成的死亡（每天51人）超过 海洛因过量致死人数最多，占所有与毒品有关的死亡人数的近五分之一。估计负担 2005年，美国医疗保健系统的支出为95亿美元，2005年估计增加到每年725亿美元。 2014.几个联邦机构的一个关键建议是在开处方前使用尿液药物检测（UDT 阿片类药物，以确定过量（尿液中阿片类药物的预期水平以上）或滥用意图转售（低或 不存在阿片类药物，尽管患者声称相反）。UDT的当前策略涉及定性筛选 对于阳性病例，随后使用HPLC或GC/MS进行定量。筛选免疫测定 使用需要有经验的人员、时间和实验室设置的台式分析仪。医生们 无法获得内部检测的患者必须将患者样本送去筛查。因此， 在每次就诊时，患有慢性疼痛的每个患者都会对治疗造成不可接受的延迟， 其次是大多数医生。在医生办公室快速、经济实惠、外行可操作的护理点UDT 将有助于快速诊断问题，并有可能阻止流行病。BreviTest Technologies已 开发了一种低成本的便携式分析仪，可在10分钟的运行时间内进行快速定量ELISA检测。 样品被装载到放置在分析仪中的盒中，并且机器人机构控制分析仪的操作。 抗体缀合的磁性纳米颗粒通过连续的流体威尔斯孔的运动，其中增强了 混合模式实质上减少了每个ELISA步骤所需的时间。这种创新的方法使 实现快速、便携、全自动ELISA检测，其准确度可与标准品相媲美 实验室ELISA在SBIR第一阶段项目中，BreviTest将开发和优化阿片类药物的ELISA检测， 使用BreviTest机器人分析仪检测尿液。本项目的具体目标是：（1）开发具有竞争力的 使用BreviTest分析仪平台进行阿片类药物的ELISA。我们将确定最佳试剂浓度 用于免疫测定并表征BreviTest平台中测定的性能。性能 参数包括动态范围、重复性和定量限。(2)执行有限的证明- 与当地病理学合作，对分析仪进行去识别尿液样本的概念性现场研究 实验室BreviTest提供了一个独特的平台来创建一个ELISA测试，用于快速定量 尿液药物水平在医生的办公室，这将是一个宝贵的工具，使更有效的剂量， 患者，为降低毒性和提高生活质量铺平了道路。

PROJECT SUMMARY The United States is in the midst of a prescription opioid epidemic. Deaths from misuse (51 daily) exceed deaths from heroin overdose and account for nearly one-fifth of all drug-related deaths. The estimated burden on the US healthcare system was $9.5 billion in 2005 and increased to an estimated $72.5 billion annually in 2014. A key recommendation of several federal agencies is to use urine drug testing (UDT) before prescribing opioids to establish overdosing (above expected levels of opioids in urine) or misuse with intent to resell (low or absent opioids despite patient claims to the contrary). Current strategy for UDT involves a qualitative screening immunoassay, followed by quantification using HPLC or GC/MS for positive cases. Screening immunoassays use benchtop analyzers that require experienced personnel, time, and a laboratory setup. Physicians who do not have access to in-house testing have to send out patient samples for screening. Thus, laboratory testing of every patient suffering from chronic pain at every visit imposes unacceptable delays to treatment and is not followed by most physicians. A quick, affordable, layman operable, point of care UDT in the physician's office will help in rapid diagnosis of problems and potentially halt the epidemic. BreviTest Technologies has developed a low-cost, portable analyzer to perform a rapid, quantitative ELISA test within a 10-minute run time. The sample is loaded into a cartridge that is placed in the analyzer, and a robotic mechanism controls the movement of antibody-conjugated magnetic nanoparticles through successive fluid wells, where enhanced mixing patterns substantially reduce the time required for each ELISA step. This innovative approach enables the implementation of a rapid, portable, fully automated ELISA test with accuracy comparable to a standard laboratory ELISA. In this SBIR Phase I project, BreviTest will develop and optimize an ELISA test for opioids in urine using the BreviTest robotic analyzer. The Specific Aims for the project are: (1) Develop a competitive ELISA for opioids using the BreviTest analyzer platform. We will determine the optimal reagent concentrations for the immunoassay and characterize performance of the assay in the BreviTest platform. Performance parameters will include dynamic range, repeatability, and limit of quantification. (2) Perform a limited proof-of- concept field study of the analyzer on de-identified urine samples in collaboration with a local pathology laboratory. BreviTest offers a unique platform to create an ELISA test for performing rapid quantifications of urine drug levels at the physician's office, which will be an invaluable tool to render more effective dosing to patients, paving the way towards lower toxicity and a better quality of life.