Expert view: How high-content platforms keep pace with the changing face of cell-based drug screening

For the next generation of cell biologists, 3D cell culture and analysis has opened doors to taking applied research one step further.

High-content confocal analysis systems have continued to keep pace with the changing face of cell biology, allowing scientists to successfully image and quantify 3D in a more efficient fashion.

Artificially created 3D environments, in which biological cells are permitted to grow or interact with their surroundings in all three dimensions, are leading the industry. Unlike 2D environments, 3D cell cultures, like spheroids and organoids, allow cells in vitro to grow in all directions, similar to how they would likely behave in vivo.

However, screening in 3D environments can be challenging and often requires key pieces of technologies to come together in a work fl ow driven process. These range from growing and plating spheroids and organoids to treating them with clearing agents so the fluorescent probes can penetrate better, to allow visualisation and quantification of sub-cellular markers, that could change in response to treatment.

Every key piece of this work fl ow needs to be carefully considered and optimised. Moving to a U-Bottom plate that allows spheroids to settle makes drug treatment and washing easier and can drastically improve the quality of data gathered. Careful consideration also needs to be given to the fluorescent probes used in experiments, since some will penetrate more easily and further into 3D cell cultures than others. Longer imaging times will require antifades to protect against photobleaching when studying self-assembling spheroids. For those 3D cell cultures requiring culturing in an extracellular matrix, clearing agents will be required to allow better penetration of fluorescent labels.

Finally, one of the biggest challenges is the analysis of these 3D cultures in a High-Content Screening background. Penetration of thicker samples necessitates the use of confocal imaging modes. Improvement in imaging depth definitely requires a move towards laser-based systems rather than LED light sources. In this fast paced world of drug discovery, generating, storing, managing, and retrieving large amounts of images and data especially for addressing 3D biology is a real challenge, but a crucial need to getting scientists what they want quickly. Thermo Fisher Scientific™ has been working towards providing cutting edge solutions for all stages of the 3D cell culture workflow, from cell culture through to HCA, and is meeting all of these challenges head on. The introduction of the Thermo Scientifi c™ CellInsight™ CX7 LZR HCA platform with HCA Studio™ software and STORE database management system offers the perfect answer to the new age 3D cell based assay Phenom. Read more here: https://