CAREER: Feedback Control of Micro-Fluidic Systems and the Bio-Chemical Particles Inside Them

研究将集中在生物分子的反馈控制和微流体系统内的液体包。目标是控制微流体包的路径和形状，以及包内生物/化学颗粒的轨迹和化学反应。这将促进新的微流体系统，如微型药物输送系统，它将允许现有系统在嘈杂的现实世界条件下工作。具体的控制任务将包括：同时控制许多粒子，以便在不同的细胞、病毒和细菌之间进行有针对性的碰撞；通过电引起的表面张力使液滴精确地移动、分裂和连接；以及单个粒子的形状控制。例如，众所周知，流体流动可以使DNA链拉直。我们最大的挑战是创造一个流场，它只能解开DNA链的一小部分，并使特定的蛋白质击中未包裹部分的开始。反馈控制需要集成设备、传感、控制算法和驱动。这种系统集成提出了基础研究的挑战。我们将解决四个开放的关键领域，这些领域与我们在流体动力学和控制方面的核心专业知识相匹配。1)实时传感器处理：从传感器数据实时推断流体包和生物颗粒的位置、类型、形状和性质。例如，我们将通过使用PIV（粒子图像测速）测量周围的流体流动，并通过有效地解决反向流入到形状的数学问题，推断出细胞的形状，直至几十纳米的分辨率。2)控制算法设计：根据传感器数据，计算合适的执行器响应。对于观察到的粒子位置，找到电极电压以使粒子在期望的方向上移动。3)控制实现：我们的控制器必须实时运行。这提出了重要的计算问题，包括控制器缩减和有限感知的状态估计。4)建模：以上三个步骤都依赖于对手头系统的可量化理解。这四个步骤将在我们实验室的微流体系统和我们合作者实验室的系统上实施。研究将主要集中在主题二：控制算法设计。更广泛的影响这项提议旨在联合不同学科的研究。1) Hinman大学生创业ceo项目支持的微流体设计大赛：参赛队伍由工程、物理、化学、生物和商学院的学生组成。本科团队将在修完必要的微制造课程后设计和制造微系统。成功的团队将通过CEO项目将他们的想法转化为商业计划（该项目为本科生提供开办和管理企业所需的工具，参见www.hinmanceos.umd.edu）。该竞赛将与women In Engineering （WIE）项目合作，作为一种招募工具，吸引女性和代表性不足的少数族裔从事科学、系统研究和创业。2)注重多学科本科生研究：本科生将参与创建实验，开发控制算法和测试设备，他们将在与我的团队合作的公司和政府实验室进行实习。3)集成控制和微/纳米语言：控制和微/纳米社区使用不同的技术语言。例如，现有的微流体模型不适合进行控制设计。在下一届AIAA航空航天科学会议和展览上，我将主持一个微流体建模与设计研讨会，届时这两个领域的研究人员将齐聚一堂。未来的研讨会将在微系统和控制会议上组织。这些研讨会将着重于将物理微系统控制挑战转化为可处理的控制理论问题。

Intellectual MeritResearch will focus on feedback control of bio-molecules and of liquid packets inside micro-fluidicsystems. The goal is to control the path and shape of micro-fluidic packets, and the trajectories andchemical reactions of bio/chem particles inside the packets. This will facilitate new micro-fluidic systemssuch as miniaturized drug delivery systems, and it will allow existing systems to function in noisy realworld conditions. Specific control tasks will include: steering of many particles at once for targetedcollisions between different cells, viruses, and bacteria; precision moving, splitting, and joining ofdroplets by electrically induced surface tension forces; and shape control of individual particles. For example, it is known that fluid flow can straighten DNA chains. Our grand challenge is to create a flow field that only unwraps a small portion of the DNA chain and makes a specific protein hit the start of that unwrapped section. Feedback control requires the integration of devices, sensing, control algorithms, and actuation. Such system integration raises fundamental research challenges. We will address four key areas that are open and which match our core expertise in fluid dynamics and control. 1) Real time sensor processing: Infer the position, type, shape, and properties of fluid packets and bio particles from the sensor data in real time. For example, we will infer the shape of cells down to tens of nanometers resolution by measuring the surrounding fluid flow using PIV (particle image velocimetry) and by efficiently solving an inverse inflow-to-shapel mathematics problem. 2) Control algorithm design: Based on the sensor data, compute the appropriate actuator response. For observed particle positions, find the electrode voltages to move the particles in the desired directions. 3) Control implementation: Our controllers must function in real time. This raises significant computational issues including controller reduction and state estimation from limited sensing. 4) Modeling: All three steps above rely on a quantifiable understanding of the systems at hand.These four steps will be implemented on micro fluidic systems in our lab and on systems in the labs ofour collaborators. The research will focus primarily on topic two: control algorithm design.Broader ImpactThis proposal aims to unite research from different disciplines. The outreach plan reflects this aim:1) Micro fluidics design competition supported by the Hinman undergraduate entrepreneurship CEOprogram: Each team in the competition will consist of students from engineering, physics, chemistry,biology, and the business school. Undergraduate teams will design and fabricate micro systems aftertaking pre-requisite micro fabrication courses. Successful teams will transition their ideas intobusiness plans through the CEO program (the program provides undergraduates with the toolsrequired to start and manage a business, see www.hinmanceos.umd.edu). In collaboration with theWomen In Engineering (WIE) program, the competition will be used as a recruiting tool to attractwomen and under-represented minorities to science, systems research, and entrepreneurship.2) Strong focus on multi-disciplinary undergraduate research: Undergraduate students will be involvedin creating the experiments, developing the control algorithms, and testing the devices, and they willundertake internships at the companies and government labs with which my group collaborates.3) Integrating the languages of control and micro/nano: The controls and micro/nano community speakdifferent technical languages. For example, existing micro fluidic models are not suitable for controldesign. I will chair a micro fluidic ilmodeling versus designli workshop at the next AIAA AerospaceSciences Meeting and Exhibit which will bring together researchers from these two communities.Future workshops will be organized at micro-systems and control conference. These workshops willfocus on translating physical micro-systems control challenges into tractable control theory questions.