Design and Control of a Piezo Drill for Robotic Piezo-Driven Cell Penetration

Abstract

Cell penetration is an indispensable step in many cell surgery tasks. Conventionally, cell penetration is achieved by passively indenting and eventually puncturing the cell membrane, during which undesired large cell deformation is induced. Piezo drills have been developed to penetrate cells with less deformation. However, existing piezo drills suffer from large lateral vibration or are incompatible with standard clinical setup. Furthermore, it is challenging to accurately determine the time instance of cell membrane puncturing; thus, the time delay to stop piezo pulsing causes cytoplasm stirring and cell damage. This letter reports a new robotic piezo-driven cell penetration technique, in which the piezo drill device induces small lateral vibrations and is fully compatible with standard clinical setup. Techniques based on corner-feature probabilistic data association filter and motion history images were developed to automatically detect cell membrane breakage by piezo drilling. Experiments on hamster oocytes confirmed that the system is capable of achieving a small cell deformation of 5.68 $\pm$ 2.74 $\mu$ m (vs. 54.29 $\pm$ 10.21 $\mu$ m by passive approach) during cell penetration. Automated detection of membrane breakage had a success rate of 95.0%, and the time delay between membrane breakage and piezo-vibration stoppage was 0.51 $\pm$ 0.27 s vs. 2.32 $\pm$ 0.98 s by manual stoppage of piezo pulsing. This reduced time delay together with smaller cell deformation led to higher oocyte post-penetration survival rate (92.5% vs. 77.5% by passive approach, n = 80 cells).