Automatic Cell Micromanipulation System With Adaptive Visual Servoing

Cell micromanipulation is an important experimental method of biomedical research,which is widely used in drug research and development,toxicology research,assisted reproduction and genetic engineering.Traditional manual cell micromanipulation requires a long time of training,which is complex and easy to cause the operator fatigue.Even so,the manual micromanipulation has low efficiency and it has no uniform quantification standard.The manual micromanipulation has low operating accuracy and high risk of contamination too.It lacks of reproducibility,which is contradictory to the rapid development of cells and the need of batch operation.So automation becomes an inevitable trend in the development of cell micromanipulation.Visual feedback,the most accessible and direct feedback,is an essential element for automatic micromanipulation system.System automation requires visual algorithms to process images quickly,accurately,and in real time.Therefore,aimed at the problems above,this paper has carried on the following researches.Firstly,an automatic focusing method is researched for cell manipulation.Several kinds of sharpness evaluation algorithms are compared based on accuracy and execution time,and Brenner gradient algorithm are selected.Automatic and fast cell autofocus experiments are achieved based on the selected algorithm and search strategy.The automatic focusing method reduces complexity and cost of system and improves the level of automation.Then,the cell and micropipette are adaptively identified and located.Image processing algorithm for early embryo is optimized from aspects of precision and fastness.Algorithm of convex hull detection for blastomere is proposed from aspects of refinement and safety of cell manipulation.The deformation of the cell is visualized which lays the foundation for the study of cell mechanical properties.In view of the adverse effects of uneven illumination,impurity of culture medium and individual differences on visual feedback,an anti-interference and adaptive cell localization algorithm is proposed,which can automatically adjust the parameters of the adaptive binarization in image processing process in the complex environments.20 images in the different zebrafish embryo microinjection experiments are processed in real time,with a success rate of 100%for cell detection and location.In addition,the algorithm based on template matching is used to realize the accurate positioning of the injection needle.The experiment of 16 real-time images is carried out to verify the effectiveness of the algorithm.Finally,based on real-time image processing,visual servoing control is achieved.Fourteen visual served microinjection experiments are conducted with 100%success rate.Experimental results shows that the proposed auto-focusing algorithm is effective,and auto-focusing motion is robust and with high precision.The proposed image processing algorithms can accurately locate targets in real time and have good adaptability,which can meet the requirements of high precision and automatic operation of cell micromanipulation.The proposed system is compact and has high degree of automation,which is conducive to the intellectual property autonomy of cell micromanipulation technology.