title: Comparisons of optical pH and dissolved oxygen sensors with traditional electrochemical probes during mammalian cell culture.
abstract: Small-scale upstream bioprocess development often occurs in flasks and multi-well plates. These culturing platforms are often not equipped to accurately monitor and control critical process parameters; thus they may not yield conditions representative of manufacturing. In response, we and others have developed optical sensors that enable small-scale process monitoring. Here we have compared two parameters critical to control in industrial cell culture, pH and dissolved oxygen (DO), measured with our optical sensors versus industrially accepted electrochemical probes. For both optical sensors, agreement with the corresponding electrochemical probe was excellent. The Pearson Correlations between the optical sensors and electrochemical probes were 98.7% and 99.7%, for DO and pH, respectively. Also, we have compared optical pH sensor performance in regular (320 mOsm/kg) and high-osmolality (450 mOsm/kg) cell culture media to simulate the increase in osmolality in pH-controlled cultures. Over a pH range of 6.38-7.98 the average difference in pH readings in the two media was 0.04 pH units. In summary, we have demonstrated that these optical sensors agree well with standard electrochemical probes. The accuracy of the optical probes demonstrates their ability to detect potential parameter drift that could have significant impact on growth, production kinetics, and protein product quality. We have also shown that an increase in osmolality that could result from controlling pH or operating the reactor in fed-batch mode has an insignificant impact on the functionality of the pH patches.
authors.affiliation: Center for Advanced Sensor Technology, Department of Chemical and Biochemical Engineering, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Xudong
authors.initials: X
authors.lastname: Ge
authors.forename: Yordan
authors.initials: Y
authors.lastname: Kostov
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Brorson
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Moreira
authors.forename: Govind
authors.initials: G
authors.lastname: Rao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D019149:Bioreactors; D015374:Biosensing Techniques / Q000295:instrumentation*; D002138:Calibration; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival; D003470:Culture Media; D004563:Electrochemistry / Q000295:instrumentation* / Q000379:methods; D006825:Hybridomas / Q000166:cytology*; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology; D055095:Optics and Photonics / Q000295:instrumentation*; D009994:Osmolar Concentration; D010100:Oxygen / Q000032:analysis*
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media; D007074:Immunoglobulin G; D010100:Oxygen