Development of a closed-loop control system for plasma medicine

血浆医学闭环控制系统的开发

基本信息

批准号：
10558618
负责人：
Francois Berthiaume
金额：
$ 42.69万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10558618
关键词：
Acceleration Address Atmosphere Atmospheric Pressure Biological Biological Assay Biological Markers Biology Biosensor Calcium Cell Death Cells Chemicals Chemistry Chronic Clinical Clinical Trials Complex Dermatologic Detection Development Devices Disease model Dose Electromagnetic Fields Elements Engineering Ensure Epithelium Feedback Feeds Foundations Gases Goals Grant Hour Hydrogen Peroxide In Situ In Vitro Inbred BALB C Mice Individual Investigation Late Effects Link Machine Learning Malignant Neoplasms Measurable Measurement Measures Medical Medicine Metabolism Methods Microscope Modeling Monitor Mus Necrosis Nitric Oxide Nitrogen North Carolina Outcome Outcome Assessment Outcome Measure Output Oxidation-Reduction Oxygen Performance Plasma Plasma Enhancement Play Process Property Reactive Oxygen Species Regulation Reproducibility Research Role Signal Transduction Pathway Skin wound healing Solid System Temperature Testing Therapeutic Therapeutic Uses Time Tissues Universities Virus Diseases Wound models clinical application clinical effect diabetic ulcer epithelial wound experience extracellular healing in vitro Model in vivo in vivo Model innovation ionization keratinocyte mouse model pathogenic bacteria pathogenic virus response sensor side effect temporal measurement translational applications wound wound closure wound healing

项目摘要

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.

项目概要血浆医学是一个有前途的、相对较新的领域，包括发现和开发冷等离子体（又称非热等离子体、非平衡等离子体或大气等离子体）的生物医学应用。寒冷的通过使用强电磁场电离大气中的气体，可以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，会产生一系列影响从细胞代谢和功能的微妙变化到程序性或坏死性细胞死亡，取决于血浆特性（或血浆量）。在涉及血浆的治疗策略中，输送的剂量是治疗成功的重要决定因素。次优血浆剂量可能无效，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，没有存在有效血浆剂量的实时测量。血浆的测定和控制输送目前，剂量依赖于评估血浆二级或三级效应的经验结果测量暴露后数小时至数天。迫切需要使用冷血浆输送进行调节同时测量与生物学和临床相关的初级血浆效应物（标记物）定义血浆剂量所需的结果（终点）。这笔赠款的目的是开发端点基于血浆的治疗的检测策略，使用血浆促进伤口修复作为终点，氧化还原电位（ORP）作为主要可检测标记。假设存在一个链接绝对 ORP 和细胞反应之间的关系，使我们能够开发一种基于 ORP 传感器的方法监测血浆剂量并将该信息输入闭环控制系统。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系统将根据终点结果来调节血浆输送。合作研究开发工作将结合体内伤口愈合模型（罗格斯大学）和体外的经验上皮伤口修复模型和血浆生物学（德雷克塞尔大学），具有设备工程专业知识和等离子体化学（北卡罗来纳州立大学）。拟议的研究框架围绕以下内容具体目标： (1) 建立 CAP 剂量范围、可测量的生物参数和使用体内和体外伤口愈合模型的伤口愈合结果； (2) 将传感器输出与体外划痕试验中的细胞反应； (3)开发调节等离子体闭环控制系统送货; (4)在体外和体内挑战并优化控制器。我们专注于端点检测和伤口愈合的反馈控制将促进这种特殊治疗用途的开发工作等离子，但也将为将终点检测应用于其他转化应用提供坚实的基础冷血浆，包括皮肤病、癌症以及病毒和细菌感染的治疗病原体。