Neonatal Opioid Screening Using Aptamers and Compensated Interferometry

项目摘要/摘要 美国正在经历一场规模空前的阿片类药物流行。超过6个出局 10%的药物过量现在与阿片类药物有关，导致每天约90人死亡。对经济的影响 据估计，每年疫情的总成本超过750亿美元，主要来自卫生和社会成本 与处方阿片类药物的使用有关[疼痛医学。2011；12(4)：657-67。2013；14(10)：1534-47]。新的 可能会采取立法行动来解决这场危机。 新生儿禁欲综合征是一种由母亲在出生前使用阿片类药物引起的疾病 今天在美国出生的所有新生儿中约有6%患有严重的疾病 由于这种流行病，发病率正在迅速增加。一种快速筛查试验的可用性 可以在护理点对所有新生儿进行管理的措施将允许早期干预， 降低治疗成本，减轻弱势群体的痛苦 病人群体。此外，出生后不久需要手术的新生儿通常会忍受 持续静脉注射吗啡或相关化合物，导致发育 同样的综合症，因为这些婴儿也会对他们的处方药上瘾。 提供一个平台来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这些疼痛管理治疗的使用， 根据个别新生儿的需要进行个性化，减少上瘾的可能性和 由此产生的并发症，包括有害的神经影响。 此FastTrack SBIR项目的目的是扩展我们的初步成果和 为商业化做好准备。我们已经证明了后向散射 干涉测定法可以与高度选择性的DNA适体结合使用，以灵敏地 并在一微升尿中准确检测阿片类药物及其初级尿代谢物 样品，在样品引入我们的设备后不到一分钟内。在这个节目中，我们将 通过以下方式改进此平台：(I)修改仪器以降低每次测试和许可的成本 多路复用；(Ii)开发检测所有最常见的 这些样本中滥用的阿片类药物及其代谢物；和(Iii)测试新的关注点 仪器和分析与金标准质谱学实验室测试对比，使用REAL 从目标患者人群中获取的样本。 一个经验丰富、协作的团队，包括适体和分析开发 碱基对生物技术公司的科学家、范德比尔特公司的后向散射干涉测量专家 来自范德比尔特大学的临床医生BioTex，Inc.的医疗器械工程师 健康中心，有翻译/商业化经验的新生儿专家将会工作 共同实现这些目标。监管专家将就检测、软件和 用于医院、诊所和其他场所的仪器设计，此类测试可能在这些场所进行 被部署。

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.