High-throughput Integrated Magneto-electrochemical Exosome (HiMEX) platform to identify neurodevelopmental markers associated with pre and postnatal oxycodone exposure

怀孕期间和怀孕后对处方阿片类药物的依赖对母亲的健康构成重大风险 还有孩子。接触阿片类药物的新生儿会经历药物戒断综合征，风险增加 认知障碍。然而，对这些暴露在空气中的新生儿的临床护理受到了当前的挑战 知识方面的根本差距：缺乏可靠的生物标记物来客观评估新生儿患癌症的风险 药物暴露：人们对出生前和出生后使用阿片类药物如何影响后代知之甚少，特别是在 神经发育，而且没有可靠的生物标志物可用于客观评估新生儿受药物影响的风险- 曝光。我们寻求开发一种新的检测平台来有效地监测新生儿羟考酮的暴露。 (Oxy)。我们的方法将基于两种创新的方法：细胞外小泡(EVS)作为生物标记物 IMEX(集成磁电化学外切体)作为传感器平台。目标1.我们将确定电动汽车 高风险氧暴露的蛋白质特征。我们将使用我们的啮齿动物模型来模拟子宫内和出生后 氧气暴露。将从接触氧气的后代的大脑中收集和分析EV，通过定量的 蛋白质组学用于鉴定差异表达的蛋白质。目标2.我们将实施第二代IMEX 大大扩展了分析能力。我们将通过探索一种新的IMEX检测方法来提高检测灵敏度 信号放大(纳米等离子)；建立统一的检测跨膜和 囊泡内标记；并构建高通量检测器(96孔板格式)。这一新系统将 用于从接触氧气的动物中筛选血浆电动汽车。这个项目的成功将产生 氧暴露下脑源性EVS的全面蛋白质数据以及EVS作为一种关键疾病的潜力 生物标志物。此外，所获得的见解将为进一步将Himex技术扩展到临床奠定基础 验证。我们的长期目标是提供一种微创血液测试，用于风险评估和及时 对氧暴露的干预。

Dependency on prescription opioids during and after pregnancy poses a significant health risk, both to mother and child. Newborns exposed to opioids would experience a drug withdrawal syndrome and have elevated risk of cognitive disorders. Clinical care for these exposed neonates, however, is challenged by a current fundamental gap in knowledge: lack of reliable biomarkers available to objectively assess newborn's risk from drug-exposure: it is poorly understood how pre- and postnatal opioid use affects offsprings, particularly with neurodevelopment, and no reliable biomarkers are available to objectively assess a newborn's risk from drug- exposure. We seek to advance a new assay platform to effectively monitor newborns' exposure to oxycodone (oxy). Our approach will be based on two innovative approaches: extracellular vesicles (EVs) as a biomarker and iMEX (integrated magneto-electrochemical exosome) as a sensor platform. Aim 1. We will identify EV protein signatures of high-risk oxy-exposure. We will use our rodent models to emulate in-utero and postnatal oxy-exposures. EVs from brains of oxy-exposed offspring will be collected and analyzed via quantitative proteomics to identify differentially-expressed proteins. Aim 2. We will implement the second generation iMEX with significantly expand analytical capacities. We will enhance iMEX detection sensitivity by exploring a new signal amplification (nanoplasmonics); establish a unified assay to detect both transmembrane and intravesicular markers; and construct a high-throughput detector (a 96 well-plate format). This new system will be used to screen plasma EVs from oxy-exposed animals. The success of this project will generate comprehensive protein data on brain-derived EVs under oxy-exposure and critically EVs' potential as a biomarker. Furthermore, the insights gained will set the stage to further extend HiMEX technology for clinical validation. Our long-term goal is to deliver a minimally-invasive blood test for risk assessment and timely intervention for oxy-exposure.