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A Closed Loop Control System with Live Cells in the Loop

环路中有活细胞的闭环控制系统

基本信息

批准号：
10376040
负责人：
Francesco Sorrentino
金额：
$ 17.92万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10376040
关键词：
Affect Aging Autophagocytosis Biological Biological Sciences Cell Line Cell physiology Cells Cellular Stress Centers of Research Excellence Combination Drug Therapy Coupled Development Diabetes Mellitus Disease Dose Down-Regulation Engineering Environment Experimental Models Faculty Flow Cytometry Fluorescence Microscopy Goals Homeostasis Image Immune In Vitro Individual Infection Inflammation Inflammatory Insulin Intervention Investigation Knowledge Lead Liquid substance Mathematics Measurement Medical Mentors Metabolism Methods Modeling Nerve Degeneration New Mexico Nutrient Optics Outcome Output Patients Performance Personal Satisfaction Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacotherapy Physiological Processes Positioning Attribute Probability Process Reagent Regulation Research Role Sampling Schedule Science Scientific Advances and Accomplishments Signal Transduction Specialist System Systems Analysis Techniques Technology Testing Therapeutic Thinking Time Toxic effect Uncertainty Universities Up-Regulation Vesicle Work base biological systems control theory design dosage experimental study improved infancy innovation instrument mathematical model member model design response success therapy resistant treatment optimization

项目摘要

A CLOSED LOOP CONTROL SYSTEM WITH LIVE CELLS IN THE LOOP This work proposes to develop and apply, for the ﬁrst time, control theory-derived strategies to regulate autophagy in live cells using an innovative experimental testbed with sensing and actuating capabilities. Combinations of pharmacological interventions are used extensively for the treatment of many diseases. Therefore, there is signiﬁcant potential for control theory- based treatments to enhance the well-being of patients through careful tuning of dosage delivery of multiple pharmacological reagents (PRs). Intracellular measurements of the formation of autophagy vesicles (AVs) in response to the application of various PRs will be conducted using traditional ﬂuorescence microscopy and an Amnis ImageStream Mark II Imaging Flow Cytometer, available at the University of New Mexico (UNM) Autophagy, Inﬂammation, and Metabolism in Disease Center of Biomedical Research Excellence (AIM Center), the only autophagy-focused CoBRE in the nation and in which PI Sorrentino is an Associate Member. This state-of-the-art instrument uses ﬂow cytometry and multispectral imaging to detect intracellular AVs, providing an accurate count of total AVs (the output) within individual cells. A perfusive ﬂuidic delivery system to deliver drugs (the inputs) in time and in a controlled manner will be developed as part of the proposed eﬀort. This experimental testbed will provide a proof-of-concept realization of closed-loop control of autophagy in live-cell experiments. In addition, an integrated mathematical model will be developed to describe the regulation of autophagy in live cells by considering the eﬀects of several PRs on the formation of AVs. Our control decisions will be explicated at two levels: ﬁrst, the choice of PRs to use in a combination study out of a set of available PRs; and second, the dosage function for each PR in the combination, i.e., the rate at which the PR is supplied as a function of time, with time being a continuous function. An innovative multi-scenario optimal controller will also be developed and tested to optimize the control actions in the presence of limited experimental information and uncertainty about the state of the system. The UNM AIM Center hosts a team of specialists who conduct groundbreaking research into the role of autophagy in inﬂammatory diseases and infection, and who provide mentoring opportunities for junior faculty. As an Associate Member of the AIM Center, PI Sorrentino is in a unique position within a specialized, local environment to meet with success. The long-term impact of the proposed research will be signiﬁcant, as it has considerable potential to advance scientiﬁc knowledge at the nexus of engineering and life sciences, and lead to the development of optimized therapies that could positively aﬀect the well-being of millions of patients worldwide. 1

一种含有活细胞的闭环控制系统这项工作首次提出开发和应用控制理论衍生的策略来调节活细胞中的自噬。电池使用具有传感和驱动能力的创新实验测试平台。药物组合干预措施被广泛用于治疗许多疾病。因此，控制理论具有巨大的潜力- 通过仔细调整多种药物的剂量递送，试剂（PR）。响应于应用的自噬囊泡（AV）形成的细胞内测量将使用传统荧光显微镜和Amnis ImageStream Mark II成像仪进行各种PR 流式细胞仪，可在新墨西哥州大学（UNM）获得生物医学研究卓越中心（AIM中心），全国唯一一个以自噬为重点的CoBRE， PI Sorrentino是准会员。这种最先进的仪器使用流式细胞术和多光谱成像，检测细胞内AV，提供单个细胞内总AV（输出）的准确计数。一种灌注性的麻醉剂将开发一个及时和以受控方式提供药物（投入物）的输送系统，作为拟议的好的。该实验平台将为活细胞自噬的闭环控制提供概念验证实验此外，还将建立一个完整的数学模型来描述细胞自噬的调节，活细胞，通过考虑几种PR对AV形成的影响。我们的控制决策将在两个水平：第一，从一组可用PR中选择用于组合研究的PR;第二，剂量函数对于组合中的每个PR，即，供应PR的速率作为时间的函数，时间是连续的功能一个创新的多场景优化控制器也将被开发和测试，以优化控制行动，有限的实验信息和系统状态的不确定性的存在。 UNM AIM中心拥有一个专家团队，他们对自噬的作用进行了开创性的研究，卫生组织还为初级教员提供指导机会。作为准成员在AIM中心，PI Sorrentino在专业的当地环境中处于独特的地位，可以取得成功。的拟议研究的长期影响将是重大的，因为它具有相当大的潜力，以促进科学知识在工程和生命科学的联系，并导致优化疗法的发展，可以积极地治疗全世界数百万患者的福祉。 1

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Reservoir computing with noise.

带噪声的油藏计算。

DOI：
10.1063/5.0130278
发表时间：
2023
期刊：
Chaos (Woodbury, N.Y.)
影响因子：
0
作者：
Nathe,Chad;Pappu,Chandra;Mecholsky,NicholasA;Hart,Joe;Carroll,Thomas;Sorrentino,Francesco
通讯作者：
Sorrentino,Francesco

Supermodal Decomposition of the Linear Swing Equation for Multilayer Networks.