Comparisons of optical pH and dissolved oxygen sensors with traditional electrochemical probes during mammalian cell culture

被引:79
作者
Hanson, Michael A.
Ge, Xudong
Kostov, Yordan
Brorson, Kurt A.
Moreira, Antonio R.
Rao, Govind
机构
[1] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA
[2] US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Rockville, MD 20857 USA
关键词
optical sensor; electrochemical probe; mammalian; cell culture; process monitoring; scale-up;
D O I
10.1002/bit.21320
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 99.7010, 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. Biotechnol.
引用
收藏
页码:833 / 841
页数:9
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