Abstract
3D cell culture has developed rapidly over the past 5-10 years with the
goal of better replicating human physiology and tissue complexity in the
laboratory. Quantifying cellular responses is fundamental in
understanding how cells and tissues respond during their growth cycle
and in response to external stimuli. There is a need to develop and
validate tools that can give insight into cell number, viability and
distribution in real-time, non-destructively and without the use of
stains or other labelling processes. Impedance spectroscopy can address
all of these challenges and is currently used both commercially and in
academic laboratories to measure cellular processes in 2D cell culture
systems. However, its use in 3D cultures is not straight forward due to
the complexity of the electrical circuit model of 3D tissues. In
addition, there are challenges in the design and integration of
electrodes within 3D cell culture systems.
Researchers have used a range of strategies to implement impedance
spectroscopy in 3D systems. This review examines electrode design,
integration and outcomes of a range of impedance spectroscopy studies
and multi-parametric systems relevant to 3D cell cultures. While these
systems provide whole culture data, impedance tomography approaches have
shown how this technique can be used to achieve spatial resolution. This
review demonstrates how impedance spectroscopy and tomography can be
used to provide real-time sensing in 3D cell cultures, but challenges
remain in integrating electrodes without affecting cell culture
functionality. If these challenges can be addressed and more realistic
electrical models for 3D tissues developed, the implementation of
impedance-based systems will be able to provide real-time, quantitative
tracking of 3D cell culture systems.
Keywords: 3D cell culture, impedance spectroscopy, in situ
monitoring, impedance tomography, multi-parametric sensing, real-time
monitoring.