Measuring 3D Cell Culture Viability in Multiple 3D Printed Scaffolds Within a Single Miniature Electrical Impedance Tomography Sensor

The use of 3D cell culture for tissue engineering and regenerative medicine applications often challenges conventional biochemical and optical assays. Impedance-based cellular assays have shown their potential to retrieve dielectric parameters pertaining to cell behavior such as viability, proliferation, and differentiation for 2D adherent cell culture. Herein, simultaneous 3D impedance imaging and viability measurements of multiple large (>2 mm) 3D cell cultures embedded in collagen gels are demonstrated. The method is facilitated by low-resistance 3D printed scaffolds that can hold a 3D cell–gel system throughout cell culture while being transparent to impedance imaging. It is shown in silico and in vitro that frequency-difference electrical impedance tomography (fd-EIT) can nondestructively and in a label-free way differentiate a variety of cell concentrations with a single miniature sensor in real time. This study paves the way toward the development of EIT imaging for the quantitative and noninvasive evaluation of tissue engineering products.