Scaling Up Cell Culture
Microcarrier culture is recommended for high-density cultures—in some cases, densities as high as two million cells per milliliter can be realized. Microcarrier technology lends itself to large-scale production because the frequent media changes and cell dispensing in downstream processes (such as cryopreservation) can be fully automated. The magnetic property of GEM allows the automation system to either disperse or aggregate the substrate at any stage of the process.
The BioLevitator™ is a benchtop incubator and bioreactor produced for GCS by Hamilton for cell culture on the GEM substrate. It uses programmable magnets to selectively manipulate the position and motion of the cell-coated GEM. The BioLevitator R3 (Figure 2) has touchscreen control and internal carbon dioxide and temperature regulation and can be integrated into most liquid-handling platforms.
Automated cellular systems allow rapid visualization and analysis of large groups of cells. With GEM, cells can be automatically placed directly into the assay process without removing them from the growth surface. The GEM is optically clear and nonautofluorescent allowing cells to be assayed for absorbance, fluorescence, and luminescence, as well as imaged directly.
Microcarriers as substrates in cell culture can provide a significant cost reduction. In a recent study, labor and waste expenses (measured by disposable plastic and glass biohazard waste) were reduced by 85% and 76%, respectively (Figure 3).
GCS and Hamilton are developing a high-throughput system that will automate cell culture and cell passaging, integrating up to four BioLevitators on the deck of a Microlab® STAR. This 3D CellHOST™ system will enable large-scale growth and expansion of cells using the magnetic microcarrier.
Three-dimensional microcarrier cell culture provides a solution to the current constraints in cell procurement. Specifically, substrate characteristics that include magnetism, extracellular matrix-like constituents, and the ability to be pipetted in liquid phase, all contribute to a highly automatable cell culture system that can keep up with modern high-content screening demands.