, Volume 70, Issue 6, pp 1631–1642 | Cite as

Facile development of medium optimization for antibody production: implementation in spinner flask and hollow fiber reactor

  • Chi-Hsien LiuEmail author
  • Yi-Xin Liu
  • Wei-Chi Wu
Original Article


Most bio-industrial mammalian cells are cultured in serum-free media to achieve advantages, such as batch consistency, suspended growth, and simplified purification. The successful development of a serum-free medium could contribute to a reduction in the experimental variation, enhance cell productivity, and facilitate biopharmaceuticals production using the cell culture process. Commercial serum-free media are also becoming more and more popular. However, the cell line secrets its own recombinant product and has special nutritional requirements. How can the composition of the proprietary medium be adjusted to support the specific cell’s metabolism and recombinant protein? This article uses statistical strategies to modify the commercial medium. A design of experiments is adopted to optimize the medium composition for the hybridoma cell in a serum-free condition. The supplements of peptone, ferric citrate, and trace elements were chosen to study their impact on hybridoma growth and antibody production using the response surface methodology. The stimulatory effect of the developed formulation on hybridoma growth was confirmed by the steepest ascent path. The optimal medium stimulated the hybridoma growth and antibody production in three diverse systems: a static plate, an agitated spinner flask, and a hollow fiber reactor. The cells in the developed serum-free medium had a better antibody production as compared to that in the commercial medium in the hollow fiber reactor. Our results demonstrated that the facile optimization for medium and antibody production was successfully accomplished in the hybridoma cells.


Antibody Hybridoma Medium optimization 



We express gratitude to Ministry of Science and Technology (MOST 106-2221-E-182-050), Chang Gung University (BMRP 758) and Chang Gung Memorial Hospital (CMRPD2G0282, 2H0071) for funding and supporting this research. We would also like to thank the valuable suggestion of bioreactor operation from Frank R. H. Wang, United BioPharma Inc., Hsinchu, Taiwan.

Compliance with ethical standards

Conflicts of interest

The authors would like to declare that no conflicting financial interests exist.

Supplementary material

10616_2018_255_MOESM1_ESM.docx (97 kb)
Supplementary material 1 (DOCX 97 kb)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Chemical and Materials EngineeringChang Gung UniversityTaoyuanTaiwan
  2. 2.Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human EcologyChang Gung University of Science and TechnologyTaoyuanTaiwan
  3. 3.Department of Chemical EngineeringMing Chi University of TechnologyNew Taipei CityTaiwan
  4. 4.Department of OphthalmologyChang Gung Memorial HospitalTaoyuanTaiwan
  5. 5.Graduate Institute of Biochemical and Biomedical EngineeringChang Gung UniversityTaoyuanTaiwan
  6. 6.College of MedicineChang Gung UniversityTaoyuanTaiwan

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