A High-Throughput Automated Microinjection System for Human Cells With Small Size

Abstract

This paper presents the development of an automated microinjection system with high productivity for small cells. Compared with many existing microinjection systems that are primarily designed for relatively large-scaled biological samples, the reported technology will enable an automated injection into the cells with a diameter smaller than 25 μm, which is the typical size of many human cells. Microfluidic technology has been used to design a vacuum-based cell-holding device for immobilizing cells. The cell holder employs hundreds of regular-shaped channels, and each channel is occupied by one cell. The vision-based position-tracking method is used to recognize and position the target cells automatically, in which the cell position is measured by edge template-matching method, and a bright field image is used to simplify the recognition process. A 3-DOF microrobotic system mounted with a micropipette is used to conduct cell injection task with the speed of 35 cells/min and the precision of 0.2 μm. Injection experiments on human foreskin fibroblast and human embryonic stem cell-derived ventricular cardiomyocyte were performed to demonstrate the effectiveness of the developed system. More than 1000 cells were injected with fluorescent markers. Experimental results showed that the developed injection system exhibits high productivity and accuracy, and results in a good cell survival rate after injection.