Cells naturally grow in a 3D environment, which has a direct influence on individual cell morphology and leads to the formation of complex intercellular structures. Maintaining this 3D environment is crucial to understanding cell function and signaling, as well as cellular responses to external stimuli such as pharmaceuticals and biopharmaceuticals. As a result, the use of conventional cell-culturing techniques—where cells are grown in 2D monolayers—limits the biological relevance of cell-based assays, as cell morphology, proliferation, metabolism, and expression profiles are very different than they would be in vivo. Despite this, 2D formats are still widely used as model systems in drug discovery and screening, leading to high attrition rates during development and potentially impeding the progress of new therapeutic agents.
Researchers have developed a variety of 3D cell-culturing strategies that more closely mimic the in vivo environment. The most appropriate 3D approach will depend on both application and cell type, and can be divided into scaffold-based formats—which employ matrix materials of either natural or synthetic origin, such as polystyrene or collagen—and scaffold-free strategies—such as forcing cells to form microtissues in hydrogels.
Although 3D cell-culturing strategies overcome many of the inherent drawbacks of 2D techniques, they can be more challenging in terms of handling and logistics. Manual handling of cell cultures, even when grown on a monolayer, is a time-consuming and labor-intensive process, requiring regular media changes and replating to maintain optimal viability and proliferation. This issue may be exacerbated further by the use of 3D culturing techniques, where the increased cell density within cultures can require more frequent maintenance to ensure unimpeded cell growth.
The repetitive nature of cell-culture maintenance makes these procedures excellent candidates for automation using a liquid handling and robotics platform, such as Tecan’s Freedom EVO workstation. Integration of software-controlled, automation-friendly incubators onto these platforms eliminates the need for manual protocols and associated inter-operator variability, providing consistent and uniform cells for screening applications.
An example of this approach, which is currently under development on Tecan’s Freedom EVO platform, is the use of Reinnervate’s Alvetex Scaffold to provide 3D cell-culturing capabilities in a 96-well microplate format. This highly porous, polystyrene scaffold has a uniform and well-defined architecture intended to improve cell-to-cell interactions and generate complex, tissue-like cellular structures for the generation of more biologically relevant data. Combining this technology with liquid handling and incubation capabilities allows users to generate large quantities of consistent 3D cell cultures suitable for screening applications.
Automated maintenance of cell cultures also raises the possibility of complete workflow automation on a single platform. Use of an open architecture liquid-handling platform allows integration of a wide range of devices including readers, washers, heaters, shakers, and separation modules alongside the culturing systems, to suit the individual assay requirements of the laboratory. Development of an end-to-end solution for 3D cell-culture screening has the potential to reduce costs and accelerate the drug discovery pipeline by offering more reliable results, improving the quality of candidates for downstream development.
Filed Under: Drug Discovery
