Adapting wireless glucometer to boost opioid dependence medication compliance

物质使用障碍（SUD）是一个主要的健康问题，对医疗保健和社会成本有直接和间接的影响，估计在美国每年超过1810亿美元。阿片类药物是第二大滥用物质，丁丙诺啡（BUP）是一种有效且安全的阿片类药物依赖药物。然而，BUP仍然是一种麻醉剂，严格遵守BUP对于患者获得最佳治疗结果，防止复发和避免药物转移至关重要。依从性通常在医院就诊时通过定期和随机尿检来监测。然而，由于每次定期尿检间隔时间长、费用高、随机尿检的侵入性，这一措施不足以防止BUP转移到意外使用。因此，随机尿检价格低廉，使用方便，并向医生提供实时检测结果，同时保持患者的隐私，将提高药物依从性。虽然已经为尿液测试和电子监测开发了许多方法，但很少有测试技术能够满足上述所有要求，这可能是由于新的POC设备开发成本高，制造成本高，特别是当这些设备刚刚进入市场时。为了克服这一限制，伊利诺伊大学的Yi Lu教授小组报告了一项发现，该发现允许重新利用广泛使用的低成本个人血糖仪（PGM）来检测许多非葡萄糖目标。其创新之处在于将其抗体与非葡萄糖靶点（如BUP）的结合转化为释放转化酶，转化酶可以将蔗糖水解成葡萄糖，然后通过PGM进行量化。通过这个SHIFT奖，我们建议将正在申请专利的发现转化为商业产品。通过授权该技术并招募Lu集团的两名主要成员，GlucoSentient公司计划开发低成本的家庭尿液测试，用于BUP，去丁丙诺啡（norBUP）， BUP的主要脱烷基代谢物。通过开发与现有PGM兼容的测试条，我们将利用超过30年的PGM研究，并规避昂贵的硬件开发过程。最近成功推出的fda批准的智能手机支持的pgm将通过智能手机应用程序实现提醒、测试结果和数据分析的无线传输。I期研究的目标是证明使用智能手机连接PGM的可行性：(1)在缓冲溶液和尿液中检测10 ng/mL的BUP和norBUP；(2)研制缓冲液中BUP和norBUP的检出限为10 ng/mL的试纸条；(3)评估尿样试纸的性能。完成这些具体目标将为开发产品原型和智能手机平台的第二阶段研究铺平道路。该产品的成功应用不仅会对BUP治疗的依从性产生重大影响，还会对其他sud的治疗产生重大影响。

DESCRIPTION: Substance use disorder (SUD) is a major health problem with direct and indirect impact on healthcare and societal cost that is estimated at over $181 billion annually in the United States. Opioids are the second most abused substances and buprenorphine (BUP) is an effective and safe medication for opioid dependence. However, BUP remains a narcotic, and strict BUP compliance is critical for patients to obtain the best treatment outcome, prevent relapse, and avoid medication diversion. Compliance is commonly monitored by periodic and random urine tests at hospital visits. However, due to long intervals between each periodic urine drug test, high cost and intrusiveness of random drug testing of a patient, such a measure has not been sufficient to prevent the diversion of BUP for unintended use. Therefore random urine drug tests that are inexpensive, convenient to use, and provide real time test results to doctors while maintaining the privacy of the patients will boost medication compliance. While many methods have been developed for the urine tests and for electronic monitoring, few test technologies meet all of the above requirements, likely due to the fact that new POC devices are costly to develop and expensive to manufacture, particularly when the devices are new to the market. To overcome this limitation, Prof. Yi Lu's group at the University of Illinois has reported a discovery that allows repurposing the widely available and low-cost personal glucose meter (PGM) for detecting many non- glucose targets. The innovation lies in converting the binding of non-glucose target (e.g. BUP) by its antibody to releasing the enzyme invertase which can hydrolyze sucrose into glucose and then quantified by PGM. Through this SHIFT award, we propose to transform the patent-pending discovery into commercial products. Through licensing the technology and recruiting two key members of the Lu group, GlucoSentient, Inc. plans to develop low-cost, at-home urine tests for BUP, norbuprenorphine (norBUP), a major dealkylated metabolite of BUP using the PGM. By developing test strips that are compatible with existing PGMs, we will take advantage of over 30 years of PGM research and circumvent the costly hardware development process. The recent successful launch of FDA-approved smartphone-enabled PGMs will enable wireless transmission of reminders, test results, and data analysis through smartphone apps. The goal of the Phase I research is to demonstrate the feasibility of using a smartphone attached PGM to: (1) detect BUP and norBUP at 10 ng/mL in buffer solution and urine; (2) develop test strips for BUP and norBUP with a limit of detection of 10 ng/mL in buffer solution; and (3) assess the performance of tests strips in urine samples. Accomplishing these specific aims will pave the way for Phase II research in developing both product prototypes and the smartphone platform. Successful applications of the proposed product will have significant impact on boosting compliance for not only BUP treatment, but also treatment of other SUDs.