On-chip microelectrode impedance analysis of mammalian cell viability during biomanufacturing

Sharma, Rachita; Blackburn, Tobias; Hu, Weiwei; Wiltberger, Kelly; Velev, Orlin D.

doi:10.1063/1.4895564

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…the cell cytoplasm and the surrounding medium. 16,17 By applying an AC current to the sensing area through a pair of electrodes, the impedance of the cells is measured through the same pair of electrodes or the adjacent electrode pair, which can be used to deduce cell concentration, 18,19 cell viability 20,21 and other cell activities. 22 It is generally agreed that impedance measurements are a convenient, non-destructive and reliable approach for cell-based assays with high temporal resolution.…”

Section: A Introductionmentioning

confidence: 99%

Electrical impedance tomography for real-time and label-free cellular viability assays of 3D tumour spheroids

Yang

Bagnaninchi

et al. 2018

Analyst

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There is currently a need to culture cells in 3D to better mimic the behaviour of cells growing in the natural environment. In parallel, this calls for novel technologies to assess cell growth in 3D cell culture. In this study, we demonstrated both in silico and in vitro that cell viability inside large cell spheroids could be monitored in real time and label-free with electrical impedance tomography (EIT). Simulations using a single shell model and the effective media approximation (EMA) method were performed to prove the performance of EIT on spheroid imaging and viability monitoring. Then in vitro experiments were conducted to measure in real time a loss of cell viability in MCF-7 breast cancer spheroids when exposed to Triton X-100 and validate with conventional biochemical assays. It is shown that EIT has a spatial resolution of 1.14% and it could monitor the cell mortality over 20% of a spheroid under laboratory noise level. The reconstructed conductivity images for cell mortality induced by the chemical are clear and match the result in the cellular metabolic viability assay. Furthermore, the image reconstruction speed in the experiment was less than 0.3 seconds. Taken together, the results show the potential of EIT for non-destructive real-time and label-free cellular assays in the miniature sensor, providing physiological information in the applications of 3D drug screening and tissue engineering.

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Section: A Introductionmentioning

confidence: 99%

Electrical impedance tomography for real-time and label-free cellular viability assays of 3D tumour spheroids

Yang

Bagnaninchi

et al. 2018

Analyst

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“…As an example, impedance measurements have been used for continuous monitoring of tissue spheroids ( 62 , 84 , 85 ), as well as estimating the cell size ( 84 , 85 ), proliferation ( 62 ), evaluation of cell concentration ( 86 ) and cell viability ( 87 , 88 ). In addition, this method has been used for monitoring cells behavior by application of bulk ( 89 ) or thin film electrodes ( 90 ), on cells attached to a substrate ( 91 ), on cells in suspension ( 92 ) or on trapped single cell ( 93 ).…”

Section: Common Bioimpedance Measurement Techniques Applied In Tissuementioning

confidence: 99%

Applications of bioimpedance measurement techniques in tissue engineering

Amini

Hisdal

Kalvøy

2018

Journal of Electrical Bioimpedance

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Rapid development in the field of tissue engineering necessitates implementation of monitoring methods for evaluation of the viability and characteristics of the cell cultures in a real-time, non-invasive and non-destructive manner. Current monitoring techniques are mainly histological and require labeling and involve destructive tests to characterize cell cultures. Bioimpedance measurement technique which benefits from measurement of electrical properties of the biological tissues, offers a non-invasive, label-free and real-time solution for monitoring tissue engineered constructs. This review outlines the fundamentals of bioimpedance, as well as electrical properties of the biological tissues, different types of cell culture constructs and possible electrode configuration set ups for performing bioimpedance measurements on these cell cultures. In addition, various bioimpedance measurement techniques and their applications in the field of tissue engineering are discussed.

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“…In that study, sensor response enabled prediction of osteogenic potential in hASC populations, a result which has implications in quality-controlled biomanufacturing of stem cellbased therapies [12]. In another example, Sharma et al used impedance spectroscopy to investigate the viability of NS0 murine myeloma cells, an important cell line for production of therapeutic proteins, and found that impedance response enabled a more rapid detection of cell death than a Trypan blue staining assay as well as potential for continuous viability monitoring [13]. Narayanan et al used dielectric impedance spectroscopy for monitoring the quality of 3D bioprinted constructs [14].…”

Section: Introductionmentioning

confidence: 99%

3D bioprinting using hollow multifunctional fiber impedimetric sensors

et al. 2020

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3D bioprinting is an emerging biofabrication process for the production of adherent cell-based products, including engineered tissues and foods. While process innovations are rapidly occurring in the area of process monitoring, which can improve fundamental understanding of process-structure-property relations as well as product quality by closed-loop control techniques, in-line sensing of the bioink composition remains a challenge. Here, we report that hollow multifunctional fibers enable in-line impedimetric sensing of bioink composition and exhibit selectivity for real-time classification of cell type, viability, and state of differentiation during bioprinting. Continuous monitoring of the fiber impedance magnitude and phase angle response from 102 to 106 Hz during microextrusion 3D bioprinting enabled compositional and quality analysis of alginate bioinks that contained fibroblasts, neurons, or mouse embryonic stem cells (mESCs). Fiber impedimetric responses associated with the bioinks that contained differentiated mESCs were consistent with differentiation marker expression characterized by immunocytochemistry. 3D bioprinting through hollow multifunctional fiber impedimetric sensors enabled classification of stem cells as stable or randomly differentiated populations. This work reports an advance in monitoring 3D bioprinting processes in terms of in-line sensor-based bioink compositional analysis using fiber technology and provides a non-invasive sensing platform for achieving future quality-controlled bioprinted tissues and injectable stem-cell therapies.

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On-chip microelectrode impedance analysis of mammalian cell viability during biomanufacturing

Cited by 8 publications

References 45 publications

Electrical impedance tomography for real-time and label-free cellular viability assays of 3D tumour spheroids

Electrical impedance tomography for real-time and label-free cellular viability assays of 3D tumour spheroids

Applications of bioimpedance measurement techniques in tissue engineering

3D bioprinting using hollow multifunctional fiber impedimetric sensors

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