Real-time Continuous Intravenous Drug Monitor for Closed-Loop Anesthesia Delivery

 描述（由申请人提供）：麻醉学是解决安全性的领先医学领域，但它仍然有很长的路要走。尽管麻醉相关死亡率显著下降，但每年对接受全身麻醉的2100万美国人构成真实的危险的关键因素仍然存在，根据NIGMS，“全身麻醉剂仍然是医生使用的最危险的药物之一，特别是对老年患者和患有某些慢性全身性疾病的患者，如糖尿病。“现在很明显，麻醉的方式对安全性有着深远的影响。然而，鉴于患者人群具有高度多样性和不断变化的药理学差异，麻醉从业者没有直接的手段来了解患者在任何给定时间的精确药物血浆水平。因此，没有直接测量如何定制剂量以实现最佳安全性。这种能力将产生变革性的影响，推动麻醉实践成为一门严格的科学，从而提高患者的安全性和预后。存在可以自动调节剂量的目标控制输注系统。然而，这些都是基于血浆药物浓度的预测，通过从健康患者的小模型人群外推，导致重大的安全性问题，并缺乏FDA的批准。需要直接测量静脉内浓度以管理这些风险并获得市场批准。因此，我们建议开发第一个系统，直接测量和精确控制静脉麻醉药物浓度连续实时。我们提出了一种一次性系统，该系统利用微流体装置中的适体传感器，该微流体装置防止未修饰的全血降解，并保持无漂移定量，具有亚分钟时间分辨率和纳摩尔灵敏度。第一阶段目标的完成将提供一个概念验证系统，该系统证实了我们能够在活体家兔中真实的实时测量和控制血浆丙泊酚水平，并通过金标准LC-MS/MS方法进行验证。我们还将确定我们的反馈控制丙泊酚输注是否可以减少与标准镇静方案相比所需镇静深度的偏移，这是通过对物理刺激的反应来测试的。在第二阶段，我们将包括人类受试者，以验证我们准确测量人体丙泊酚水平的潜力。我们将提供设计改进和性能指标，为临床研究做好准备。我们希望通过私人资本或合作伙伴公司的战略投资，通过与行业合作伙伴的合作，继续进行临床阶段和FDA批准。

 DESCRIPTION (provided by applicant): Anesthesiology is the leading field of medicine in addressing safety, but it still has a long way to go. Despite significant decreases in anesthesia-related mortality, crucial factors remain that pose real hazards to the 21 million Americans that receive general anesthesia each year, and According to the NIGMS, "general anesthetics are still among the most dangerous drugs used by doctors, particularly for elderly patients and those with certain chronic, systemic diseases, such as diabetes." It is now clear that the manner in which anesthesia is delivered has a profound impact on safety. Yet, there given a patient population with highly diverse and changing pharmacological differences, practitioners of anesthesia have no direct means of knowing the precise drug plasma levels in the patient at any given time. Thus, there is no direct measure of how to tailor dosing to achieve optimal safety. Such a capability would have a transformative impact, driving the practice of anesthesia to an exacting science that will improve the safety and outcomes of patients. Target controlled infusion systems exist which can automatically adjust doses. However, these are based on a prediction of the plasma drug concentration, by extrapolating from a small model population of healthy patients, leading to major safety concerns, and an absence of FDA clearance. Direct measurement of intravenous concentrations is required to manage these risks and gain market approval. Thus, we propose to develop the first system that directly measures and precisely controls intravenous anesthetic drug concentrations continuously in real-time. We present a disposable system that exploits an aptamer sensor in a microfluidic device that prevents degradation from unmodified whole blood and maintains drift-free quantification with sub-minute time resolution, and nanomolar sensitivity. The completion of Phase I Aims will deliver a proof of concept system, which affirms our ability to measure and control plasma propofol levels in real time in live rabbits, as verified by gold standard LC-MS/MS methods. We will also determine if our feedback-controlled propofol infusion can reduce excursions from a desired depth of sedation versus standard sedation protocol as tested by response to physical stimuli. In Phase II, we will include human subjects to validate our potential to accurately measure propofol levels in humans. We will deliver design improvements and performance metrics, ready for clinical study. We expect to follow on with private capital or strategic investment from a partner company to proceed through clinical stage and FDA clearance via collaboration with industry partners.