Real-time monitoring of 3D cell culture using a 3D capacitance biosensor

Lee, Sun Mi; Han, Nalae; Lee, Rimi; Choi, In Hong; Park, Yong Bum; Shin, Jeon Soo; Yoo, Kyung Hwa

doi:10.1016/j.bios.2015.09.005

Cited by 54 publications

(35 citation statements)

References 17 publications

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“…Nevertheless, in this study, the electrode properties change as the cells are growing within the conductive hydrogel and it is consistent with other studies using conductive scaffolds (Inal et al, 2017). However, other studies with similar cell types have shown the opposite effect, with the introduction of cells increasing the overall impedance of 3D systems (Inal et al, 2017;Lee et al, 2016;Lei et al, 2018). Groeber et al (2015) are among the only published groups using the whole EIS spectrum and information provided by an equivalent circuit to monitor tissue growth in a coculture system.…”

supporting

confidence: 90%

“…This was due to an increase in gel conductivity after the addition of cells, which was attributed to the presence of gap junctions between cells that allowed electrical connection between neighboring cell membranes (Pan et al, 2019). However, other studies with similar cell types have shown the opposite effect, with the introduction of cells increasing the overall impedance of 3D systems (Inal et al, 2017; Lee et al, 2016; Lei et al, 2018).…”

Section: Impedance Measurements In 3d Cell Culturementioning

confidence: 95%

“…It has been demonstrated that the electrical properties of cells can be monitored when they are immersed within a hydrogel rather than directly attached to a planar electrode (Lee et al, 2016). Lee et al (2016) incorporated a matrix of vertical electrodes (Figure 2a) that were able to monitor the migration, proliferation, and apoptosis of cells through a gel matrix in 3D. In this system, cells were grown in an alginate hydrogel scaffold and vertical parallel electrodes were used to measure the capacitance of the system.…”

Section: Impedance Measurements In 3d Cell Culturementioning

confidence: 99%

Section: Impedance Measurements In 3d Cell Culturementioning

confidence: 99%

“…However, these devices are mainly designed for monitoring adherent cells grown in 2D or transwellbased coculture systems. Electrodes have also been integrated into a range of different 3D cell culture models and microfluidic platforms for EIS monitoring (Curto, Ferro, Mariani, Scavetta, & Owens, 2018;Lee et al, 2016;Lei, Liu, & Tsang, 2018). In particular, cell proliferation within spheroids have been successfully monitored using this technique (Bu, Diener, Frey, Kim, & Hierlemann, 2016;Lei, Lin, & Tsang, 2017;Lei, Liu, & Tsang, 2018;Pan et al, 2019).…”

mentioning

confidence: 99%

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Three‐Dimensional (3D) cell culture monitoring: Opportunities and challenges for impedance spectroscopy

León

Pupovac

McArthur

2020

Biotech & Bioengineering

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Three‐dimensional (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, nondestructively 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 multiparametric 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.

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supporting

confidence: 90%

Section: Impedance Measurements In 3d Cell Culturementioning

confidence: 95%

Section: Impedance Measurements In 3d Cell Culturementioning

confidence: 99%

Section: Impedance Measurements In 3d Cell Culturementioning

confidence: 99%

mentioning

confidence: 99%

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Three‐Dimensional (3D) cell culture monitoring: Opportunities and challenges for impedance spectroscopy

León

Pupovac

McArthur

2020

Biotech & Bioengineering

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Methods for Analyzing the Biological and Biomedical Properties of Biomaterials

Rožanc¹,

Maver²

2023

Functional Biomaterials

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Conducting Polymer Scaffolds for Hosting and Monitoring 3D Cell Culture

et al. 2017

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now clear that architectures that reproduce tissue organization in 3D are favored for studying function as first shown by Bissell and co-workers nearly 30 years ago. [5,6] Another emerging concept is the capacity for multiple cell types to auto-organize when given the appropriate mechanical cues. [7] A large variety of 3D models have been developed, with the major subtypes being spheroids/organoids, multilayered tissue like models, and scaffold models. [8] 3D tissues are frequently constructed as spheroids using hydrogel-like matrices such as Matrigel, [9] or PuraMatrix, [10] with a highly desirable degree of mechanical softness, however, there can be problems related to cost and inhomogeneity of the materials. [11] Multilayer models hold a lot of promise for applications such as skin toxicology measurements, [12] however, they cannot be easily applied for more complex tissue or organ constructs including vasculature. Considerable attention has thus focused on the development of biocompatible scaffold materials for hosting cells in 3D. A variety of synthetic and bio-derived polymers (some resorbable, some not) have been used to mimic the ECM or connective tissue. In terms of technology integration, the major advances so far for 3D cell biology have been related to materials and methods used for scaffold preparation, and integration of microfabrication techniques, for example for fluidics. As might be expected, a challenge of 3D culture over 2D is associated with the difficulty of oxygenation of tissues in the absence of vasculature. Microfluidics have gained favor for a number of reasons, including for perfusion, reduction in reagent volumes, and the fact that flow induced stress This work reports the design of a live-cell monitoring platform based on a macroporous scaffold of a conducting polymer, poly(3,4-ethylene dioxythiophene):poly(styrenesulfonate). The conducting polymer scaffolds support 3D cell cultures due to their biocompatibility and tissue-like elasticity, which can be manipulated by inclusion of biopolymers such as collagen. Integration of a media perfusion tube inside the scaffold enables homogenous cell spreading and fluid transport throughout the scaffold, ensuring long term cell viability. This also allows for co-culture of multiple cell types inside the scaffold. The inclusion of cells within the porous architecture affects the impedance of the electrically conducting polymer network and, thus, is utilized as an in situ tool to monitor cell growth. Therefore, while being an integral part of the 3D tissue, the conducting polymer is an active component, enhancing the tissue function, and forming the basis for a bioelectronic device with integrated sensing capability.

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Real-time monitoring of 3D cell culture using a 3D capacitance biosensor

Cited by 54 publications

References 17 publications

Three‐Dimensional (3D) cell culture monitoring: Opportunities and challenges for impedance spectroscopy

Three‐Dimensional (3D) cell culture monitoring: Opportunities and challenges for impedance spectroscopy

Methods for Analyzing the Biological and Biomedical Properties of Biomaterials

Conducting Polymer Scaffolds for Hosting and Monitoring 3D Cell Culture

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