面向细胞微创注射的三维常力输出柔性微定位平台的设计与控制研究

The survival rate of injected cells in microinjection is greatly influenced by the damage made to the cells. This project introduces a fully compliant, constant-force, multi-degree-of-freedom (DOF) micropositioning system to overcome the large cell deformation and large cell-wall damage caused by classical single-DOF drive micropositioning and ultrasonic-assisted microinjection techniques. A centimeter-stroke 3-DOF constant-force compliant parallel-kinematic stage driven by voice coil motors is designed as a precision positioning stage. Unlike traditional single-DOF micropositioning technique, the multi-DOF constant-force positioning is proposed to implement a high-speed injection motion of the injection pipette along with its axial direction precisely with a constant output force, so that the transverse motion and peak impact force are avoided to reduce the damage of cells. Different from existing XYZ positioning stages with small stroke or bulky structure, a novel compliant constant-force micropositioning stage with both centimeter-level large stroke and compact physical size will be devised, along with a compactness index of space mechanism proposed. To realize a constant force output, a new large-stroke bistable compliant mechanism is proposed to cancel the positive stiffness of XYZ stage module using the negative stiffness of the bistable module. The modular design idea is proposed to cater for the multi-function requirements simultaneously. To realize a precise positioning, a new second-order terminal discrete-time sliding mode control strategy will be proposed and introduced to the field of precision motion control of micropositioning stage. Based on a new discrete-time terminal sliding function, theoretical analysis is carried out to derive the reaching conditions of sliding surface and to prove the finite-time convergence property of the control algorithm. Proper methods will be proposed to select suitable control parameters in order to improve the control accuracy, to quicken the convergence speed, and to mitigate the chattering phenomenon. The research and development of such a precision micropositioning system will provide an effective approach to realize an automated cell microinjection with minimal deformation and damage of the cells, so as to enhance the survival rate of the injected cells.

细胞显微注射中实现对细胞微创伤刺膜是目前面临的关键难题，快速惯性运动穿刺微定位是解决该问题的有效途径。然而，传统单自由度微定位难以确保注射针沿纯纵向运动。本项目提出采用多自由度定常力微定位方法，提供注射针沿纵向快速惯性常力穿刺运动。内容包括：三维大行程常力柔性并联解耦平台的设计研究及其高阶终端离散滑模变结构运动控制。首次设计出厘米级行程、常力输出、结构紧凑的全柔性三平动并联解耦精密定位平台，提出模块化设计方法，以解决同时实现各功能的三维常力柔性机构的设计问题。提出新型离散二阶终端滑模变结构控制算法，并对其有限时间收敛性和离散滑模到达条件进行理论证明，以提高定位精度、加快收敛速度与抑制抖振，通过自动化细胞显微注射实验加以验证。本项目旨在对设计新型常力柔性机构与离散二阶终端滑模变结构运动控制策略奠定技术基础，对于细胞显微注射中有效减少细胞创伤，提高注射细胞存活率，具有重要的理论意义和应用价值。

细胞显微注射是指在显微环境下，采用微注射针将外源物质导入到细胞内，从而改变活体细胞的内环境，在药物输送、胚胎移植、肿瘤细胞治疗等生物医学领域的应用日益广泛。为提高注射细胞的成活率，采用快速惯性运动穿刺微定位是实现对细胞微创伤刺膜的关键技术。本项目首次提出多自由度定常力输出微定位方法，并将其应用于细胞微注射操作。项目在多维度大行程常力柔性并联机构的设计机理与实现、基于高阶终端滑模理论的精密运动控制算法的设计及其在细胞显微注射应用方面取得如下创新性成果：(1) 首次提出厘米级行程、常力输出、结构紧凑的全柔性三平动并联解耦精密定位平台的设计方法，实现了机构的模块化创新设计，发明了多款大行程、柔性恒力微定位平台；针对大挠度柔性机构，提出了非线性静力学和动力学建模方法，并采用有限元分析进行了仿真验证，为高性能柔性常力机构的设计、建模与优化提供了系统的理论和方法。(2) 提出新型二阶及三阶终端滑模变结构控制算法，并对其有限时间收敛性和离散滑模到达条件进行了理论推导证明；揭示了离散终端滑模面、离散二阶滑模面对控制误差的影响规律，得到了控制器性能相对于各控制参数变化规律以及模型干扰与不确定性的鲁棒性特点，达到了提高定位精度、加快收敛速度、抑制抖振的控制目标，为柔性常力平台机构的精密控制奠定理论基础。(3) 研制出柔性常力显微注射系统样机，采用所提出的滑模变结构精密运动控制算法，集成了视觉伺服反馈控制，解决了实现过程中的技术难题，并对斑马鱼卵细胞进行了细胞微创注射操作实验验证。本项目申请专利5个，出版专著1本，发表期刊论文30篇、会议论文37篇，相关成果获澳门特区技术发明奖二等奖。本项目成果为常力柔性机构的机械设计与控制提供了重要参考与借鉴，有助于推动在该领域的持续研究及应用。项目成果已成功应用于斑马鱼卵细胞的显微注射，还可应用到机器人常力末端执行器、人机交互界面、触觉反馈界面等。