Controlled positioning of biological cells inside a micropipette

Manipulating single cells with a micropipette is the oldest, yet still a widely used technique. This paper discusses the positioning of a single cell to a target position inside the micropipette after the cell is aspirated into the micropipette. Due to the small volume of a single cell (pico-liter) and nonlinear dynamics involved, this task has high skill requirements and is labor intensive in manual operation that is solely based on trial and error and has high failure rates. We present automated techniques in this paper for achieving this task. Computer vision algorithm was developed to track a single cell inside a micropipette for automated single-cell positioning. A closed-loop robust controller integrating the dynamics of cell motion was designed to accurately and efficiently position the cell to a target position inside the micropipette. The system achieved high success rates of 97% for cell tracking (n=100) and demonstrated its capability of accurately positioning a cell inside the micropipette within 8 seconds (vs. 25 seconds by highly skilled operators).