Development of a closed-loop control system for plasma medicine

项目摘要 血浆医学是一个很有前途的相对较新的领域，它包含了 冷等离子体的生物医学应用(又名非热、非平衡或大气等离子体)。冷的 在大气中，利用强电磁场使气体电离，产生多种形式的等离子体。 压力和环境温度。当冷等离子体应用于活细胞或组织时，其效果可能会 从细胞代谢和功能的细微变化到程序性或坏死性细胞死亡，依赖于 等离子体属性(或等离子体数量)。在涉及血浆的治疗策略中，提供的剂量是 治疗成功的重要决定因素。次优的血浆剂量可能是无效的，而血浆 超过达到预期结果所需的剂量可能会导致不良副作用。然而，没有 有效血浆剂量的实时测量是存在的。血浆的测定和受控给药 目前，剂量依赖于评估血浆二次或三次影响的结果的经验衡量标准。 在暴露后几小时到几天。迫切需要对冷血浆输送进行监管，以使用 与生物学和临床相关的初级血浆效应物(标志物)的同时测量 结果(终点)是确定血浆剂量所必需的。这笔赠款的目标是开发端点 以血浆促进的伤口修复为终点的血浆疗法的检测策略 以氧化还原电位(ORP)为主要检测指标。假设是有联系的 在绝对的ORP和细胞反应之间，允许我们开发一种基于ORP传感器的方法， 监测血浆剂量，并在一个闭环控制系统中提供这些信息。拟议的研究是 创新，因为它将使用ORP检测作为传感器控制的闭环反馈控制的基础 将根据终点结果确定的调节血浆输送的系统。协作式调查 开发工作将结合体内伤口愈合模型的经验(罗格斯大学)，在体外 上皮创伤修复模型和血浆生物学(德雷克塞尔大学)，设备工程专业 和等离子体化学(北卡罗来纳州立大学)。拟议的研究围绕以下几个方面展开 具体目标：(1)建立CAP剂量范围、可测量的生物学参数和 使用创伤愈合的体内和体外模型的创伤愈合结果；(2)传感器输出与 体外划痕试验中的细胞反应；(3)建立可调节血浆的闭环控制系统 (4)体外和体内对控释剂的挑战和优化。我们专注于终端检测和 对伤口愈合的反馈控制将促进这种特殊治疗用途的发展努力 等离子，但也将为将端点检测应用于其他翻译应用提供坚实的基础 冷血浆，包括治疗皮肤病、癌症以及病毒和细菌感染 病原体。

Project Summary Plasma medicine is a promising, relatively new field that encompasses the discovery and development of biomedical applications for cold plasma (a.k.a. non-thermal, non-equilibrium, or atmospheric plasma). Cold plasma is generated in several forms by using a strong electromagnetic field to ionize gas at atmospheric pressure and ambient temperature. When cold plasma is applied to living cells or tissues, the effects can range from subtle changes in cellular metabolism and function to programmed or necrotic cell death, dependent on plasma properties (or amount of plasma). In therapeutic strategies involving plasma, the dose delivered is an important determinant of a successful treatment. A sub-optimal plasma dose may be ineffective, while a plasma dose in excess of that required to achieve the desired outcome may cause adverse side effects. However, no real-time measure of an effective plasma dose exists. The determination and controlled delivery of a plasma dose, at present, relies on empirical measures of outcome that assess secondary or tertiary effects of plasma hours to days after the exposure. There is a critical need for regulation of cold plasma delivery that uses concurrent measurement of primary plasma effectors (markers) that correlate with biological and clinical outcomes (endpoints) necessary to define plasma dose. The objective of this grant is to develop endpoint detection strategies for plasma-based therapies, using plasma-facilitated wound repair as the endpoint and oxidation-reduction potential (ORP) as the primary detectable marker. The hypothesis is that there is a link between the absolute ORP and cellular responses, allowing us to develop an ORP sensor-based method that monitors the plasma dose and feeds this information in a closed-loop control system. The proposed research is innovative because it will use ORP detection as the basis for a sensor-controlled, closed-loop feedback control system that will regulate plasma delivery as determined by the endpoint outcome. Collaborative investigational and development efforts will combine experience in models of in vivo wound healing (Rutgers University), in vitro models of epithelial wound repair, and plasma biology (Drexel University) with expertise in device engineering and plasma chemistry (North Carolina State University). The proposed research is framed around the following specific aims: (1) Establish correlations between CAP dose ranges, measurable biological parameters and wound healing outcomes using in vivo and in vitro models of wound healing; (2) correlate sensor outputs with cellular responses in the in vitro scratch assay; (3) develop a closed-loop control system for regulated plasma delivery; and (4) challenge and optimize the controller in vitro and in vivo. Our focus on endpoint detection and feedback control for wound healing will facilitate developmental efforts for this particular therapeutic use of plasma, but will also provide a solid foundation for applying endpoint detection to other translational applications of cold plasma, including therapies for dermatological conditions, cancer, and infections by viral and bacterial pathogens.