Label-free independent quantitation of viable and non-viable cells using a multivariable multi-resonant sensor

• Published in: Bioelectrochemistry (Amsterdam, Netherlands) Netherlands), 2019-02, Vol.125, p.97-104
• Main Authors: Potyrailo, Radislav A., Dieringer, Jon, Cotero, Victoria, Lee, Yongjae, Go, Steve, Schulmerich, Matthew, Malmquist, Gunnar, Castan, Andreas, Gebauer, Klaus, Pizzi, Vincent
• Format: Article
• Language: English
• Subjects: Animals; Bioengineering; Bioreactors; Biosensing Techniques - instrumentation; Cell culture; Cell Survival; Cell suspensions; CHO Cells; Contamination; Cricetulus; Dielectric Spectroscopy - instrumentation; Drug resistance; Electric Impedance; Equipment Design; Logistics; Multi-resonant sensor; Multivariable sensing; Multivariate Analysis; Non-viable cells; Quantitation; Risk analysis; Sensitivity enhancement; Sensors; Single-use components; Suspension culture; Toxicology; Viable cells; Workflow
• ISSN: 1567-5394; 1878-562X
• DOI: 10.1016/j.bioelechem.2018.10.001

Biological cells are utilized for diverse biotechnological and bioengineering purposes ranging from the production of biopharmaceuticals, to cell therapy, “human-on-a-chip” drug and toxicology assays, and drug-resistance tests. In these and other applications, it is critical to quantify the levels of not only viable but also non-viable cells. While traditional off-line cell-staining methods are available for counting of non-viable cells, many applications cannot periodically remove cells for their off-line analysis because of the risk of contamination or workflow logistics. Here we show in-situ label-free quantitation of viable and non-viable cells with multivariable multi-resonant sensors. We used Chinese hamster ovary (CHO) cells in suspension culture in single-use bioreactors as a representative example. The resonant sensor design strategy permitted enhanced sensor sensitivity versus conventional non-resonant measurements and probed the spectral dispersion of viable and non-viable cells with multiple resonances. These capabilities of label-free in-situ analysis of cell viability can be attractive in diverse cell applications such as cell suspensions, adhered cells, and their 3D assemblages. •Non-viable cells are difficult to quantify due to their weak dielectric signatures•A new sensor independently quantifies viable and non-viable cells•Resonant sensor design enhances sensor sensitivity vs. non-resonant measurements•Multi-resonant operation probes spectral dispersion of viable and non-viable cells•Multivariable analysis provides independent transfer functions for viable and non-viable cells