Neonatal Opioid Screening Using Aptamers and Compensated Interferometry

项目概要/摘要 美国正在经历前所未有的阿片类药物流行病。超过6人出局 现在，10种药物过量与类阿片有关，导致每天约90人死亡。的经济影响 据估计，艾滋病疫情的总成本超过750亿美元/年，主要来自卫生和社会成本 与处方阿片类药物使用相关[Pain Med. 2011; 12（4）：657-67. 2013; 14（10）：1534-47]。新 可能会采取立法行动来解决这一危机。 新生儿戒断综合征是由母亲在出生前使用阿片类药物引起的， 严重的条件，折磨约6%的所有新生儿今天在美国出生， 由于这种流行病，发病率迅速上升。快速筛查测试的可用性 可以在护理点对所有新生儿进行给药， 减少治疗费用，减轻这些脆弱无助的人的痛苦和苦难， 患者人群。此外，出生后不久需要手术的新生儿往往会忍受 持续静脉输注吗啡或相关化合物，导致发展 同样的症状，因为这些婴儿也会对他们的处方药上瘾。 提供一个平台，以准确监测这些药物及其代谢物的实际水平， 这样的患者将允许更好地控制使用这些疼痛控制治疗， 根据新生儿个体的需要进行个性化，减少成瘾的可能性， 导致的并发症，包括有害的神经影响。 这个FastTrack SBIR项目的目的是扩展我们的初步结果， 为商业化做准备。我们已经证明， 干涉测量法可以与高选择性DNA适体组合使用，以灵敏地 准确检测1微升尿液中的阿片类药物及其主要尿液代谢产物 样品，在样品引入我们的设备后不到一分钟。在本节目中，我们将 通过（i）修改仪器以降低每次测试的成本并允许 多路复用;（ii）开发检测所有最常见的 滥用阿片类药物及其代谢物在这些样本;和（iii）测试新的护理点 仪器和分析与金标准质谱实验室测试，使用真实的 从目标患者人群中获得的样本。 一个经验丰富的协作团队，包括适体和检测开发 Base Pair Biotechnologies的科学家，范德比尔特的反向散射干涉测量专家 大学，BioTex，Inc.的医疗器械工程师，一位来自范德比尔特大学的临床医生 健康中心和具有翻译/商业化经验的医学专家将工作 共同实现这些目标。监管专家将就检测、软件和 仪器设计用于医院、诊所和其他场所，在这些场所中，这种测试可能 部署。

Project Summary/Abstract The United States is experiencing an opioid epidemic of unprecedented scope. More than 6 out of 10 drug overdoses are now opioid-related, resulting in ~90 deaths/day. The economic impact of the epidemic has been estimated to exceed $75B/year, primarily from health and social costs related to prescription opioid use [Pain Med. 2011; 12(4):657-67. 2013; 14(10):1534-47]. New legislative actions are likely to be taken to address the crisis. Newborn Abstinence Syndrome, which results from maternal opioid drug use prior to birth, is a serious condition that afflicts approximately 6% of all neonates born today in the U.S. and which is increasing rapidly in incidence because of this epidemic. Availability of a rapid screening test that can be administered at the point of care to all neonates would allow for early intervention, reducing costs of treatment and reducing pain and suffering for this vulnerable and helpless patient population. In addition, neonates who require surgery shortly after birth often endure continuous intravenous infusion of morphine or related compounds, which result in development of the same syndrome, as these infants also become addicted to their prescribed medications. Providing a platform to accurately monitor actual levels of these drugs and their metabolites in such patients would allow better-controlled use of these pain management treatments, personalized to the needs of the individual neonate, reducing the probability of addiction and resulting complications, which include deleterious neurological effects. The purpose of this FastTrack SBIR project is to expand upon our preliminary results and prepare for commercialization. We have already demonstrated that backscattering interferometry can be used in combination with highly-selective DNA aptamers to sensitively and accurately detect opioids and their primary urinary metabolites in one microliter urine samples, in less than a minute after sample introduction into our device. In this program, we will improve this platform by (i) modifying the instrument to reduce cost per test and permit multiplexing; (ii) develop the rest of the assay menu needed to detect all the most commonly abused opioid drugs and their metabolites in these samples; and (iii) test the new point of care instrument and assays versus gold-standard mass spectrometry lab-based tests, using real samples obtained from the target patient population. A highly experienced, collaborative team that includes aptamer and assay development scientists at Base Pair Biotechnologies, backscattering interferometry experts at Vanderbilt University, medical device engineers at BioTex, Inc., a clinician from Vanderbilt University Health Center, and a neonatologist with translational/commercialization experience will work together to achieve these goals. A regulatory expert will advise on assay, software and instrument design for use in hospitals, clinics and other venues in which such tests are likely to be deployed.