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

项目总结 美国正处于处方阿片类药物流行之中。误用死亡人数(每天51人)超过 海洛因过量导致的死亡人数占所有与毒品有关的死亡人数的近五分之一。估计的负担 2005年，美国医疗保健系统的投资为95亿美元，2005年估计增至725亿美元 2014年。几个联邦机构的一项关键建议是在开处方前使用尿液药物检测(UDT) 阿片类药物过量(尿液中阿片类药物超过预期水平)或为了转售而滥用(低或 没有阿片类药物，尽管患者声称相反)。目前UDT的策略包括定性筛查 免疫分析，阳性病例用高效液相色谱或气相色谱/质谱仪定量。筛选免疫分析方法 使用需要经验丰富的人员、时间和实验室设置的台式分析仪。这样做的医生 无法获得内部检测的患者必须将患者样本送出进行筛查。因此，实验室检测 每一个在每次就诊时遭受慢性疼痛的患者都会造成不可接受的延误治疗，而不是 紧随其后的是大多数医生。医生办公室里一个快速、负担得起、外行可操作的医疗点UDT 将有助于快速诊断问题，并有可能遏制疫情。布雷迪测试技术公司已经 开发了一种低成本、便携的分析仪，可以在10分钟的运行时间内进行快速、定量的ELISA检测。 样本被装入放在分析器中的卡盒中，机器人机构控制 抗体偶联磁性纳米颗粒在连续的流体井中的移动，其中增强 混合模式大大减少了每个酶联免疫吸附试验步骤所需的时间。这一创新方法使 实施一种快速、便携、全自动的ELISA法，其准确度可与标准相当 实验室酶联免疫吸附试验。在这个SBIR第一阶段项目中，布雷迪测试公司将开发和优化一种针对阿片类药物的ELISA检测方法 使用布莱维测试机器人分析仪进行尿液分析。该项目的具体目标是：(1)发展具有竞争力的 使用布莱维测试分析仪平台进行阿片类药物的酶联免疫吸附试验。我们将确定最佳试剂浓度 用于免疫分析，并表征该分析在BreviTest平台中的性能。性能 参数将包括动态范围、重复性和量化限制。(2)进行有限度的以下证明- 尿样分析仪与局部病理相结合的概念现场研究 实验室。BreviTest提供了一个独特的平台来创建一种用于执行快速定量的 医生办公室的尿药浓度，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.