1 Department of Micro- and Nanotechnology, Technical University of Denmark2 Bioanalytics, Department of Micro- and Nanotechnology, Technical University of Denmark3 Fluidic Array Systems and Technology, Department of Micro- and Nanotechnology, Technical University of Denmark4 BioLabChip, Department of Micro- and Nanotechnology, Technical University of Denmark5 University of Oslo6 Oslo University Hospital7 Risø National Laboratory for Sustainable Energy, Technical University of Denmark8 Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics, Center, Technical University of Denmark
A bioimpedance platform is presented as a promising tool for non-invasive real-time monitoring of the entire process of three-dimensional (3D) cell culturing in a hydrogel scaffold. In this study, the dynamics involved in the whole process of 3D cell culturing, starting from polymerisation of a bare 3D gelatin scaffold, to human mesenchymal stem cell (MSC) encapsulation and proliferation, was monitored over time. The platform consists of a large rectangular culture chamber with four embedded vertical gold plate electrodes that were exploited in two- and three terminal (2T and 3T) measurement configurations. By switching between the different combinations of electrode couples, it was possible to generate a multiplexing-like approach, which allowed for collecting spatially distributed information within the 3D space. Computational finite element (FE) analysis and electrochemical impedance spectroscopic (EIS) characterisation were used to determine the configurations' sensitivity field localisation. The 2T setup gives insight into the interfacial phenomena at both electrode surfaces and covers the central part of the 3D cell culture volume, while the four 3T modes provide focus on the dynamics at the corners of the 3D culture chamber. By combining a number of electrode configurations, complementary spatially distributed information on a large 3D cell culture can be obtained with maximised sensitivity in the entire 3D space. The experimental results show that cell proliferation can be monitored within the tested biomimetic environment, paving the way to further developments in bioimpedance tracking of 3D cell cultures and tissue engineering.
Biosensors and Bioelectronics, 2015, Vol 63, p. 72-79
Bioimpedance; 3D cell culture; Gelatin scaffold; Multiplexed measurements; Three-terminal impedance; Sensitivity field distribution