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Controlled release of nutrients to mammalian cells cultured in shake flasks

Authors

  • Swati Hegde,

    1. Chemical Engineering and Process Development, National Chemical Laboratory, Council of Scientific and Industrial Research, Pune 411008, India
    2. National Institute of Technology Karnataka, Mangalore 575025, India
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  • Tejal Pant,

    1. Chemical Engineering and Process Development, National Chemical Laboratory, Council of Scientific and Industrial Research, Pune 411008, India
    2. Hislop School of Biotechnology, Nagpur 440 001, India
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  • Ketaki Pradhan,

    1. Chemical Engineering and Process Development, National Chemical Laboratory, Council of Scientific and Industrial Research, Pune 411008, India
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  • Manohar Badiger,

    1. Polymer Science and Engineering, National Chemical Laboratory, Council of Scientific and Industrial Research, Pune 411008, India
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  • Mugdha Gadgil

    Corresponding author
    1. Chemical Engineering and Process Development, National Chemical Laboratory, Council of Scientific and Industrial Research, Pune 411008, India
    • Chemical Engineering and Process Development, National Chemical Laboratory, Council of Scientific and Industrial Research, Pune 411008, India
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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. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012

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