Model-Based Robotic Cell Aspiration: Tackling Nonlinear Dynamics and Varying Cell Sizes

Aspirating a single cell from the outside to the inside of a micropipette is widely used for cell transfer and manipulation. Due to the small volume of a single cell (picoliter) and nonlinear dynamics involved in the aspiration process, it is challenging to accurately and quickly position a cell to the target position inside a micropipette. This letter reports the first mathematical model that describes the nonlinear dynamics of cell motion inside a micropipette, which takes into account oil compressibility and connecting tube0027;s deformation. Based on the model, an adaptive controller was designed to effectively compensate for the cell position error by estimating the time-varying cell medium length and speed in real time. In experiments, small-sized cells (human sperm, head width: $\sim$300A0;$\mu$m), medium-sized cells (T24 cancer cells, diameter: $\sim$1500A0;$\mu$m), and large-sized cells (mouse embryos, diameter: $\sim$9000A0;$\mu$m) were aspirated using different-sized micropipettes for evaluating the performance of the model and the controller. Based on aspirating 150 cells, the model-based adaptive control method was able to complete the positioning of a cell inside a micropipette within 6 seconds with a positioning accuracy of $\pm$300A0;pixels and a success rate higher than 94%.