title: Controlled release of nutrients to mammalian cells cultured in shake flasks.
abstract: Though cell culture-based protein production processes are rarely carried out under batch mode of operation, cell line and initial process development operations are usually carried out in batch mode due to simplicity of operation in widely used scale down platforms like shake flasks. Nutrient feeding, if performed, is achieved by bolus addition of concentrated feed solution at different intervals, which leads to large transient increases in nutrient concentrations. One negative consequence is increased waste metabolite production. We have developed a hydrogel-based nutrient delivery system for continuous feeding of nutrients in scale down models like shake flasks without the need for manual feed additions or any additional infrastructure. Continuous delivery also enables maintaining nutrient concentrations at low levels, if desired. The authors demonstrate the use of these systems for continuous feeding of glucose and protein hydrolysate to a suspension Chinese Hamster Ovary (CHO) culture in a shake flask. Glucose feeding achieved using the glucose-loaded hydrogel resulted in a 23% higher integral viable cell density and an 89% lower lactate concentration at the end of the culture when compared with a bolus-feed of glucose.
authors: Chemical Engineering and Process Development, National Chemical Laboratory, Council of Scientific and Industrial Research, Pune 411008, India.
authors: Swati
authors: S
authors: Hegde
authors: Tejal
authors: T
authors: Pant
authors: Ketaki
authors: K
authors: Pradhan
authors: Manohar
authors: M
authors: Badiger
authors: Mugdha
authors: M
authors: Gadgil
mesh_terms: D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods*; D006224:Cricetinae; D003470:Culture Media / Q000737:chemistry*; D005260:Female; D005502:Food; D005947:Glucose / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism
chemical_list: D003470:Culture Media; D020100:Hydrogels; D019344:Lactic Acid; D005947:Glucose