Automated Macro-Micro Manipulation for Robotic Microinjection with Computer Vision

Extensive research efforts have been made toward automating the microinjection of biological cells by leveraging micro-robotic technologies. However, to best knowledge of the authors, there is no report on the automation of the time-consuming process: moving the injection tools (a micropipette, a grippers, etc.) and cells into the field of view (FOV) of microscope from the macro FOV(outside the microscopic FOV). This paper presents a novel macro-micro conversion strategy, and a grid detection and positioning algorithm to automate the time-consuming step of moving the injection tools and cells to the microscopic FOV. The proposed solution can free the technician from the laborious hand-eye coordination operations for moving the injection tools and cells to the target position within the microscopic FOV. Furthermore, this paper proposes an auto-focusing algorithm to automate the operation step: moving down the gripper from the air outside the culture media and then precisely clamping a cell in the liquid environment for injection. In the proposed solution, the active window-based auto-focusing algorithm is developed to solve the challenging problem: the image information is lost due to the “viscous effect” taking place when the gripper jaw touches the water surface. The proposed solutions are tested and validated by the microinjection experiments of zebrafish embryos using the in-house develop micro-robotic system. The technologies and strategies proposed in this paper significantly improve the automation level of the cell microinjections, and can be easily extended to any other micromanipulation of biological cells.