Premium
Estimating cell specific oxygen uptake and carbon dioxide production rates for mammalian cells in perfusion culture
Author(s) -
Goudar Chetan T.,
Piret James M.,
Konstantinov Konstantinov B.
Publication year - 2011
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.646
Subject(s) - carbon dioxide , respiratory quotient , oxygen , respiration , perfusion , chinese hamster ovary cell , chemistry , zoology , biochemistry , biology , medicine , botany , receptor , organic chemistry
We present robust methods for online estimation of cell specific oxygen uptake and carbon dioxide production rates (q O2 and q CO2 , respectively) during perfusion cultivation of mammalian cells. Perfusion system gas and liquid phase mass balance expressions for oxygen and carbon dioxide were used to estimate q O2 , q CO2 and the respiratory quotient (RQ) for Chinese hamster ovary (CHO) cells in perfusion culture over 12 steady states with varying dissolved oxygen (DO), pH, and temperature set points. Under standard conditions (DO = 50%, pH = 6.8, T = 36.5°C), q O2 and q CO2 ranges were 5.14–5.77 and 5.31–6.36 pmol/cell day, respectively, resulting in RQ values of 0.98–1.14. Changes to DO had a slight reducing effect on respiration rates with q O2 and q CO2 values of 4.64 and 5.47, respectively, at DO = 20% and 4.57 and 5.12 at DO = 100%. Respiration rates were lower at low pH with q O2 and q CO2 values of 4.07 and 4.15 pmol/cell day at pH = 6.6 and 4.98 and 5.36 pmol/cell day at pH = 7. Temperature also impacted respiration rates with respective q O2 and q CO2 values of 3.97 and 4.02 pmol/cell day at 30.5°C and 5.53 and 6.25 pmol/cell day at 37.5°C. Despite these changes in q O2 and q CO2 values, the RQ values in this study ranged from 0.98 to 1.23 suggesting that RQ was close to unity. Real‐time q O2 and q CO2 estimates obtained using the approach presented in this study provide additional quantitative information on cell physiology both during bioprocess development and commercial biotherapeutic manufacturing. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011