Label-Free Monitoring of 3D Tissue Models via Electrical Impedance Spectroscopy

Finite element simulation of the impedance response of a vascular segment as a function of changes in electrode configuration

“…Two dimensional (2D) cell cultures have been used as in vitro cell models for decades, however; a traditional two dimensional cell culture lacks the cell-cell communications in three dimensions as well as influential proteins that can be found only in a three dimensional (3D) extracellular matrix. In this way a 2D cell culture fails to mimic in vivo tissue complexity ( 1 ). Whereas, the cell-cell communication in a 3D environment in which the cells are both connected to each other and the extracellular matrix, forms a complex and dynamic system which adds a new dimension to the in vitro situations ( 2 ).…”

“…Whereas, the cell-cell communication in a 3D environment in which the cells are both connected to each other and the extracellular matrix, forms a complex and dynamic system which adds a new dimension to the in vitro situations ( 2 ). 3D tissue models due to their close resemblance to an in vivo environment, make it possible to study the physiological responses of the cells in their native condition such as exchanging oxygen, nutrients and waste as well as monitoring their structural features ( 1 , 3 ). Moreover, the 2D and 3D cell cultures differ not only quantitatively due to their dimensions but also qualitatively due to the cell behaviors such as: cellular morphology, proliferation rates, cell–extracellular matrix interactions ( 4 ), migration ( 5 ), gene expression, differentiation, signaling ( 6 ), physiological function, and electrophysiological properties ( 2 , 7 ).…”

“…Proper electrode configuration is substantial in establishing an optimized measurement set-up with precise performance, and includes electrode geometry, layout, dimension, structure and material ( 1 , 3 ). Due to the importance of the dimensions of the electrodes, in some studies, theoretical calculations are performed to design the shape and size of the electrodes, prior to the experimental measurements ( 3 , 18 , 19 , 20 ).…”

“…Lempka and coworkers ( 30 ) studied optimization of the signal to noise ratio and capability of silicon based microelectrode arrays for recording neural activities as a function of changing the electrode contact size. Wang and colleagues ( 31 ) investigated variations in the sensitivity of interdigitated microelectrode arrays as the result of changes in electrode dimension as well as frequency for electric cell-substrate impedance sensing ( 1 ).…”

“…It also demonstrates the dependency of impedance and its real and imaginary components on the cell compositions such as cell membrane and intra and extracellular fluids ( 16 ). COMSOL Multiphysics is one of the simulation softwares that can demonstrate current conduction paths through 3D tissue models in multi-frequency bioimpedance measurements and in this way be employed as a practical tool in finding the optimized measurement set-up for monitoring 3D tissue models ( 1 ).…”