染色体显微操作系统关键技术研究
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摘要
生物工程与微电子技术、新材料技术和新能源技术并列为影响未来国计民生的四大科学技术支柱。生物工程中诸如细胞器移植、基因注入、染色体微切等技术均涉及到显微操作，其中染色体微分离、微切割与微克隆技术在染色体的进化、基因组结构的研究、基因的分离与定位及物理图谱的构建等方面有着广泛的应用。但与此同时，染色体显微切割装备又是制约该技术的主要瓶颈之一。本文通过对现有染色体显微操作系统进行分析，以提高切割精度及效率为目标，采用宏微双驱动机构开发了新的具有多自由度冗余驱动的染色体显微操作系统，并对其性能设计、标定及精度分析等问题进行了研究，主要内容如下：
（1）针对现有染色体显微操作系统自由度低、工作空间小等不足，提出了基于宏微双驱动机构的染色体显微操作系统。从操作平台构型、各机构尺寸设计、驱动器及传感器的选择、配套生物仪器的选择等方面介绍了该系统各组成部分的设计思路及参数选取。
（2）根据玻璃针法进行染色体切割的特点及染色体显微操作系统的组成提出染色体切割的过程应分为宏动运动及微动运动两个部分，随后分别对6-PPPS宏动台、6-PSU宏动台及6-PSS微动台进行运动学分析，再分别针对宏动及微动两种情况计算各驱动副的驱动量用于控制程序编译。
（3）提出了用于并联机构运动学标定的滚动迭代标定法。该方法通过激光跟踪仪测量移动副及动平台的位姿变化，逐段滚动迭代求出各连杆的误差参数。通过使用滚动迭代标定法对6-PPPS宏动台进行标定并与普通标定方法进行比较，证明了该方法能够有效解决大量误差参数同时计算时运算结果不收敛以及计算时间长的问题。
（4）提出用于精度分析的EMGJI矩阵及相应的分析方法，可在精度分析时根据机构参数与动平台位姿之间的相互关系提前对运算结果进行筛选，从而减少求导时间，提高计算效率。通过使用EMGJI矩阵对6-PPPS宏动台及6-PSU宏动台进行精度分析并与普通方法进行比较，证明了该分析方法能有效减少精度分析时的计算量。
（5）对玻璃针针尖在染色体切割过程中的受力弯曲情况进行了分析与建模。通过实验分析了进针角度及表面摩擦力对针尖弯曲程度的影响，并对小麦染色体进行试切割。
Bioengineering shows great effect on the national economy, together withmicroelectronics, advanced materials technology and new energy technology. Most of itstechnologies such as organelle transplantation, gene injection and chromosome microdissection involve micro manipulation. Chromosome micro dissection is widely used onthe research of chromosome evolution and genome structure, etc. However, chromosomemicro manipulator is the key factor that influences the development of chromosomemicro dissection.
This article aims to increase the chromosome dissection accuracy and efficiency. Byanalyzing current chromosome micro manipulation systems, this article proposes a novelmulti-DOF redundant chromosome micro dissection system along with the analysis of itsperformance design, calibration and accuracy. The major contents are as follows:
(1) According to the disadvantages of current chromosome micro dissectionmanipulator such as low DOF and small work space, etc. a novel macro micro dual drivechromosome dissection system was proposed. Both design idea and parameter selectionsof its components are shown. Work space and resolution are all measured both for macroand micro manipulators.
(2) The chromosome dissection process, which is proposed based on thecharacteristics of chromosome dissection, is composed of two separate parts. One part ismacro movement, another is micro movement. The corresponding kinematic analysis of 6-PPPS macro manipulator,6-PSU macro manipulator and6-PSS micro manipulator areincluded along with the macro and micro movements.
(3) A new external calibration method named rolling iterative calibration methodwas proposed. This method utilizes laser tracker to measure the displacements of all thelinear joints and the pose of the moving platform. Besides, it can solve the errorparameters one after another rather than all together. Comparing the proposed methodwith common method on the6-PPPS macro manipulator, the results can demonstrate thatrolling iterative calibration method can solve the non-convergence problem duringmassive calculation.
(4) A method for accuracy analysis on non-redundant parallel robots with identicalserial limbs was proposed. By introducing a second level partial derivative matrix calledEMGJI matrix, the influences of geometry parameters acting on the moving platformthrough joint variables can be studied. The traditional differential method usuallyconducts partial derivative on all parameters. However, according to the rules weobtained, certain parameters can be excluded in advance from the calculation. Simulationbased on the6-PPPS and the6-PSU macro manipulators shows that calculation time onaccuracy analysis drops significantly for the proposed method comparing with traditionalmethod.
(5) The deformation model of the glass needle during chromosome dissection hasbeen built. The influences on the deformation through puncture angle and surface frictionhas been described. The chromosome dissection experiment also demonstrates thevalidation of the proposed system.
（1）针对现有染色体显微操作系统自由度低、工作空间小等不足，提出了基于宏微双驱动机构的染色体显微操作系统。从操作平台构型、各机构尺寸设计、驱动器及传感器的选择、配套生物仪器的选择等方面介绍了该系统各组成部分的设计思路及参数选取。
（2）根据玻璃针法进行染色体切割的特点及染色体显微操作系统的组成提出染色体切割的过程应分为宏动运动及微动运动两个部分，随后分别对6-PPPS宏动台、6-PSU宏动台及6-PSS微动台进行运动学分析，再分别针对宏动及微动两种情况计算各驱动副的驱动量用于控制程序编译。
（3）提出了用于并联机构运动学标定的滚动迭代标定法。该方法通过激光跟踪仪测量移动副及动平台的位姿变化，逐段滚动迭代求出各连杆的误差参数。通过使用滚动迭代标定法对6-PPPS宏动台进行标定并与普通标定方法进行比较，证明了该方法能够有效解决大量误差参数同时计算时运算结果不收敛以及计算时间长的问题。
（4）提出用于精度分析的EMGJI矩阵及相应的分析方法，可在精度分析时根据机构参数与动平台位姿之间的相互关系提前对运算结果进行筛选，从而减少求导时间，提高计算效率。通过使用EMGJI矩阵对6-PPPS宏动台及6-PSU宏动台进行精度分析并与普通方法进行比较，证明了该分析方法能有效减少精度分析时的计算量。
（5）对玻璃针针尖在染色体切割过程中的受力弯曲情况进行了分析与建模。通过实验分析了进针角度及表面摩擦力对针尖弯曲程度的影响，并对小麦染色体进行试切割。
Bioengineering shows great effect on the national economy, together withmicroelectronics, advanced materials technology and new energy technology. Most of itstechnologies such as organelle transplantation, gene injection and chromosome microdissection involve micro manipulation. Chromosome micro dissection is widely used onthe research of chromosome evolution and genome structure, etc. However, chromosomemicro manipulator is the key factor that influences the development of chromosomemicro dissection.
This article aims to increase the chromosome dissection accuracy and efficiency. Byanalyzing current chromosome micro manipulation systems, this article proposes a novelmulti-DOF redundant chromosome micro dissection system along with the analysis of itsperformance design, calibration and accuracy. The major contents are as follows:
(1) According to the disadvantages of current chromosome micro dissectionmanipulator such as low DOF and small work space, etc. a novel macro micro dual drivechromosome dissection system was proposed. Both design idea and parameter selectionsof its components are shown. Work space and resolution are all measured both for macroand micro manipulators.
(2) The chromosome dissection process, which is proposed based on thecharacteristics of chromosome dissection, is composed of two separate parts. One part ismacro movement, another is micro movement. The corresponding kinematic analysis of 6-PPPS macro manipulator,6-PSU macro manipulator and6-PSS micro manipulator areincluded along with the macro and micro movements.
(3) A new external calibration method named rolling iterative calibration methodwas proposed. This method utilizes laser tracker to measure the displacements of all thelinear joints and the pose of the moving platform. Besides, it can solve the errorparameters one after another rather than all together. Comparing the proposed methodwith common method on the6-PPPS macro manipulator, the results can demonstrate thatrolling iterative calibration method can solve the non-convergence problem duringmassive calculation.
(4) A method for accuracy analysis on non-redundant parallel robots with identicalserial limbs was proposed. By introducing a second level partial derivative matrix calledEMGJI matrix, the influences of geometry parameters acting on the moving platformthrough joint variables can be studied. The traditional differential method usuallyconducts partial derivative on all parameters. However, according to the rules weobtained, certain parameters can be excluded in advance from the calculation. Simulationbased on the6-PPPS and the6-PSU macro manipulators shows that calculation time onaccuracy analysis drops significantly for the proposed method comparing with traditionalmethod.
(5) The deformation model of the glass needle during chromosome dissection hasbeen built. The influences on the deformation through puncture angle and surface frictionhas been described. The chromosome dissection experiment also demonstrates thevalidation of the proposed system.
引文
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