Micro-Scale Biological Process Automation: Modelling, Sensing and Control

在过去的十年里，人们对发展先进的细胞外科技术越来越感兴趣。生物医学研究和医学界对使用这种技术处理细胞和胚胎的需求越来越大，这给实验室带来了压力，要求他们提高这一过程的吞吐量和成功率。目前，这些过程由训练有素的技术人员手动进行。为了满足日益增长的需求，必须开发这些任务自动化的最先进技术。我们以前在机器人和自动化领域的经验应用于大规模制造，以及我们在生物工程方面的发展，在过去的6-7年中，涉及单细胞胚胎的注射，细胞注射中注射力的控制，细胞注射的视觉伺服控制，以及3D MEMS装配自动化，使我们能够独特地研究微尺度生物技术任务的自动化。在本提案中，我们将调查以下挑战所需的微尺度细胞处理技术自动化。本拟议研究的目的是调查单细胞手术的自动化与自动化机器人生物操作系统。我们建议的工作包括：（i）开发一个自动化系统，为机器人手术的单个细胞进行图案化;（ii）开发传感和控制策略，用于使用PZT致动的细胞膜切割器进行细胞膜穿孔的机器人自动化;（iii）使用电场致动，在具有视觉反馈的闭环控制下对内部细胞器进行成像，开发闭环视觉控制器，允许细胞重新定向以进行手术; ㈣开发基于视觉和力的轨迹生成、感测和控制方法，以确保细胞的精确穿孔; ㈤开发使用激光镊子移除细胞体的自动机器人方法。这项工作将推进最先进的技术，创造新的技术，允许进行自动化细胞手术。

The last decade has witnessed a growing interest in the development of advanced techniques for what is now referred to single as cell surgery. An increasing demand for processing of cells and embryos using this technique, from both the biomedical research and medical communities, is placing pressure on labs carrying out his work to increase both the throughput and success rate of this process. Currently, these processes are carried out manually by highly trained technicians. To meet increasing demand, advances in the state-of-the-art of the automation of these tasks must be developed. Our previous experience in the robotics and automation field applied to large scale manufacturing, and developments we have made in bioengineering in the last 6-7 years, involving injection of single cell embryos, control of injection forces in the cell injection, visual servo control for cell injection, and 3D MEMS assembly automation has uniquely positioned us to investigate the automation of micro-scale biotechnology tasks. In this proposal, we will investigate the following challenges required in micro-scale cell processing technology automation.This proposed research aims to investigate automation of single cell surgery with an automated robotic bio-manipulation system. Our proposed work includes: (i) Develop an automated system to pattern individual cells for robotic surgery; (ii) Develop sensing and control strategies for robotic automation of cell membrane perforation using a PZT actuated cell membrane cutter; (iii) Using electric field actuation, under closed-loop control with visual feedback to image internal cell organelles, develop closed-loop vision based controllers allowing cells to be re-oriented for surgery; (iv) Develop vision and force based trajectory generation, sensing and control methodologies to ensure precise perforation of cells; (v) Develop automated robotic approaches for the removal of cell bodies using laser tweezers. This work will advance the state of the art, creating new technologies to permit automated cell surgery to be carried out.