Automated vision-based selection and placement of single cells in microwell array formats

Abstract

A robotic manipulation system for automated selection and transfer of individual living cells of interest to analysis locations is presented. The system is the first in a series of operational components comprising an integrated system for the analysis of cell expression and metabolism at the single cell level. In our approach, we begin with a commonly used cell transfer technique, which uses glass capillary micropipettes to aspirate and release cells. Using a vision-based feedback closed-loop control process, two individual three-axis robotic stages are used to position the micropipette tip in proximity to the cell of interest. The cell is aspirated and the tip is moved to a target location, where the cell is then dispensed. For our initial application, the target location for living cells of interest is a microwell containing sensors that measure metabolic parameters. The system, when complete with fully integrated functionality, will offer a robust and flexible technology for cell selection and manipulation. Applications for this technology include precise tools for multi-parameter analysis of single cells, cell patterning, tissue engineering, and cell surgery.