Automation of the organ-on a chip assay: automated culture, imaging and analysis of angiogenesis

There is a critical need for biological model systems that better resemble human biology. Three-dimensional (3D) cell models and organ-on-a-chip structures representing various tissues were successfully used for studying complex biological effects, tissue architecture, and functionality. The OrganoPlate® was developed as an organ-on-a-chip platform allowing the formation of 3D microfluidic-based, long-term cultures of live cells. However, the complexity of 3D models remains a hurdle for its wide adoption in research and drug screening. Automation of the cell culture, assays, and analysis can provide the necessary tools to facilitate and scale up the use of organ-on-a-chip (OoC) systems.
Here we describe a workflow for automation of organ-on-a-chip culture, as well as monitoring, and automated cell analysis. The automated method utilizes an integrated work-cell comprising several instruments that allow the automation and monitoring of cell culture. The high-content imaging system also enables the characterization of 3D cell model development, as well as testing the effects of compounds. The integrated system includes the ImageXpress® Micro Confocal High-Content Imaging System, an automated CO2 incubator and liquid handler (Biomek i7), and collaborative robot. We developed methods for automation of cell seeding, media exchange, and for monitoring the development and growth of 3D vasculature. In addition, the method facilitates automated compound testing and evaluation of toxicity effects. We have used the angiogenesis assay as an example for the automation process.