title: Bioimpedance monitoring of 3D cell culturing--complementary electrode configurations for enhanced spatial sensitivity.
abstract: 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.
authors: Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet Building 423, Kgs. Lyngby 2800, Denmark.
authors: Chiara
authors: C
authors: Canali
authors: Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet Building 423, Kgs. Lyngby 2800, Denmark.
authors: Arto
authors: A
authors: Heiskanen
authors: Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet Building 423, Kgs. Lyngby 2800, Denmark.
authors: Haseena Bashir
authors: HB
authors: Muhammad
authors: Department of Physics, University of Oslo, Oslo, Norway; Department of Biomedical and Clinical Engineering, Oslo University Hospital, Oslo, Norway.
authors: Per
authors: P
authors: Høyum
authors: Department of Biomedical and Clinical Engineering, Oslo University Hospital, Oslo, Norway.
authors: Fred-Johan
authors: FJ
authors: Pettersen
authors: Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet Building 423, Kgs. Lyngby 2800, Denmark.
authors: Mette
authors: M
authors: Hemmingsen
authors: Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet Building 423, Kgs. Lyngby 2800, Denmark.
authors: Anders
authors: A
authors: Wolff
authors: Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet Building 423, Kgs. Lyngby 2800, Denmark.
authors: Martin
authors: M
authors: Dufva
authors: Department of Physics, University of Oslo, Oslo, Norway; Department of Biomedical and Clinical Engineering, Oslo University Hospital, Oslo, Norway.
authors: Ørjan Grøttem
authors: ØG
authors: Martinsen
authors: Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet Building 423, Kgs. Lyngby 2800, Denmark. Electronic address: jenny.emneus@nanotech.dtu.dk.
authors: Jenny
authors: J
authors: Emnéus
mesh_terms: D015374:Biosensing Techniques; D018929:Cell Culture Techniques; D058266:Dielectric Spectroscopy; D004566:Electrodes; D020342:Finite Element Analysis; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology*; D023822:Tissue Engineering
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin
keywords: 3D cell culture; Bioimpedance; Gelatin scaffold; Multiplexed measurements; Sensitivity field distribution; Three-terminal impedance