Skip to main content

In Situ Magnetic Separation on Pilot Scale: A Tool for Process Optimization

  • Chapter
  • First Online:
Upscaling of Bio-Nano-Processes

Part of the book series: Lecture Notes in Bioengineering ((LNBE))

  • 937 Accesses

Abstract

This study describes the design and development of an in situ magnetic separation process (ISMS) based on the use of ion exchange functionalized magnetic particles. ISMS as a tool for in situ product removal (ISPR) has the potential to increase the performance of a biotechnological production process comprehensively by improving the bioprocess itself and the downstream processing simultaneously. The successful implementation of this concept requires the systematic examination and optimization of the different ISMS subsystem. Hence, this report presents detailed characterization data for the magnetic particle system, the magnetic separator, and the bioprocess. For each system, specific requirements were defined and subsequently applied to identify suitable process components. In this context always economic considerations were also accounted to enable the application of this new process as cost-efficiently as possible. Especially the selection and modification of a magnetic particle system and the development of a low-cost magnetic separator were subjected to these basic criteria. For the final verification of the ISMS effects, all components were brought together in a pilot scale system and used to perform cultivation with integrated ISPR. The results of this cultivation were compared to reference cultivations without ISMS to quantify the effects on the upstream processing. In addition, a detailed analysis of the efficiency of purification was performed to evaluate the consequences on the downstream processing.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arpanaei A et al (2010) Surface modification of chromatography adsorbents by low temperature low pressure plasma. J Chromatogr A 1217(44):6905–6916

    Article  CAS  Google Scholar 

  • Atkinson B, Sainter P (1982) Development of downstream processing. J Chem Technol Biotechnol 32(1):100–108

    Article  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1):248–254

    Article  CAS  Google Scholar 

  • Cerff M et al (2013a) Semi—continuous in situ magnetic separation for enhanced extracellular protease production–modeling and experimental validation. Biotechnol Bioeng 110(8):2161–2172

    Google Scholar 

  • Cerff M et al (2013b) In situ magnetic separation of antibody fragments from Escherichia coli in complex media. BMC biotechnol 13(1):44

    Google Scholar 

  • Dickson JS, Koohmaraie M (1989) Cell-Surface Charge Characteristics and Their Relationship to Bacterial Attachment to Meat Surfaces. Appl Environ Microbiol 55(4):832–836

    CAS  Google Scholar 

  • Ditsch A et al (2006) Ion-exchange purification of proteins using magnetic nanoclusters. Biotechnol Prog 22(4):1153–1162

    Article  CAS  Google Scholar 

  • Ebner NA et al (2007) Filter capacity predictions for the capture of magnetic microparticles by high-gradient magnetic separation. IEEE Trans Magn 43(5):1941–1949

    Article  Google Scholar 

  • Fish NM, Lilly MD (1984) The Interactions between Fermentation and Protein Recovery. Bio-Technology 2(7):623–627

    Article  CAS  Google Scholar 

  • Franzreb D, Hoell D (1999) High gradient magnetic separator. EP Patent 0,920,916

    Google Scholar 

  • Franzreb M et al (2006) Protein purification using magnetic adsorbent particles. Appl Microbiol Biotechnol 70(5):505–516

    Article  CAS  Google Scholar 

  • Freeman A, Woodley JM, Lilly MD (1993) In situ product removal as a tool for bioprocessing. Bio-Technology 11(9):1007–1012

    Article  CAS  Google Scholar 

  • Gavrilescu M, Chisti Y (2005) Biotechnology—a sustainable alternative for chemical industry. Biotechnol Adv 23(7–8):471–499

    Article  CAS  Google Scholar 

  • Greiner R et al (2013) Production of partially phosphorylated myo-inositol phosphates using phytases immobilised on magnetic nanoparticles. Bioresour Technol 142:375–383

    Google Scholar 

  • Heeboll-Nielsen A et al (2004) Superparamagnetic cation-exchange adsorbents for bioproduct recovery from crude process liquors by high-gradient magnetic fishing. Sep Sci Technol 39(12):2891–2914

    Article  CAS  Google Scholar 

  • Hoffmann C, Franzreb M, Hoell WH (2002) A novel high-gradient magnetic separator (HGMS) design for biotech applications. IEEE Trans Appl Supercond 12(1):963–966

    Article  Google Scholar 

  • Hubbuch JJ et al (2001) High gradient magnetic separation versus expanded bed adsorption: a first principle comparison. Bioseparation 10(1–3):99–112

    Article  CAS  Google Scholar 

  • Idriss EE et al (2002) Extracellular phytase activity of Bacillus amyloliquefaciens FZB45 contributes to its plant-growth-promoting effect. Microbiology-Sgm 148:2097–2109

    CAS  Google Scholar 

  • Jahanshahi M, Partida-Martinez L, Hajizadeh S (2008) Preparation and evaluation of polymer-coated adsorbents for the expanded bed recovery of protein products from particulate feedstocks. J Chromatogr A 1203(1):13–20

    Article  CAS  Google Scholar 

  • Jenzsch M et al (2006) Open-loop control of the biomass concentration within the growth phase of recombinant protein production processes. J Biotechnol 127(1):84–94

    Article  CAS  Google Scholar 

  • Käppler T (2008) In: Prozessintensivierung durch feldunterstützte Bioseparation: Elektrofiltration und in situ Magnetseparation, in Faculty of chemical engineering and process engineering. Universitiy Karlsruhe, Karlsruhe

    Google Scholar 

  • Käppler TE et al (2008) Characterization of magnetic ion-exchange composites for protein separation from biosuspensions. J Biosci Bioeng 105(6):579–585

    Article  Google Scholar 

  • Käppler T et al (2009) In situ magnetic separation for extracellular protein production. Biotechnol Bioeng 102(2):535–545

    Article  Google Scholar 

  • Kerovuo J et al (1998) Isolation, characterization, molecular gene cloning, and sequencing of a novel phytase from Bacillus subtilis. Appl Environ Microbiol 64(6):2079–2085

    CAS  Google Scholar 

  • Kopaciewicz W et al (1983) Retention model for high-performance ion-exchange chromatography. J Chromatogr 266:3–21

    Google Scholar 

  • Langmuir I (1918) The adsorption of gases on plane surfaces of glass, mica and platinum. J Am Chem Soc 40(9):1361–1403

    Article  CAS  Google Scholar 

  • Maury TL et al (2012) Use of high-gradient magnetic fishing for reducing proteolysis during fermentation. Biotechnol J 7(7):909–918

    Article  CAS  Google Scholar 

  • Norde W, Buijs J, Lyklema H (2005) 3 Adsorption of globular proteins. Fundam Interface Colloid Sci 5:1–59

    Article  Google Scholar 

  • OBrien SM, Thomas ORT, Dunnill P (1996) Non-porous magnetic chelator supports for protein recovery by immobilised metal affinity adsorption. J Biotechnol 50(1):13–25

    Google Scholar 

  • Safarik I, Ptackova L, Safarikova M (2001) Large-scale separation of magnetic bioaffinity adsorbents. Biotechnol Lett 23(23):1953–1956

    Article  CAS  Google Scholar 

  • Scholz A, Cerff M, Posten C (2011) In situ product removal (ISPR) of functional proteins from prokaryotic cultivations by high specific magnetic separation. In: AFS 24th Annual conference. AFS Society, Louisville

    Google Scholar 

  • Schügerl K (2000) Integrated processing of biotechnology products. Biotechnol Adv 18(7):581–599

    Article  Google Scholar 

  • Stark D, Stockar U (2003) In situ product removal (ISPR) in whole cell biotechnology during the last twenty years. In: Stockar U et al (eds) Process integration in biochemical engineering. Springer, Heidelberg, pp 149–175

    Google Scholar 

  • Takors R (2004) Ganzzell-ISPR-Prozessentwicklung: Chancen und Risiken. Chem Ing Tech 76(12):1857–1864

    Article  CAS  Google Scholar 

  • Viloria-Cols ME, Hatti-Kaul R, Mattiasson B (2004) Agarose-coated anion exchanger prevents cell-adsorbent interactions. J Chromatogr A 1043(2):195–200

    Article  CAS  Google Scholar 

  • Westers L, Westers H, Quax WJ (2004) Bacillus subtilis as cell factory for pharmaceutical proteins: a biotechnological approach to optimize the host organism. Biochim Biophys Acta-Mol Cell Res 1694(1–3):299–310

    Article  CAS  Google Scholar 

  • Woodley JM et al (2008) Future directions for in situ product removal (ISPR). J Chem Technol Biotechnol 83(2):121–123

    Article  CAS  Google Scholar 

  • Zhang J, Greasham R (1999) Chemically defined media for commercial fermentations. Appl Microbiol Biotechnol 51(4):407–421

    Article  CAS  Google Scholar 

  • Zhang QX et al (1983) Increased production of alpha-amylase by bacillus-amyloliquefaciens in the presence of glycine. Appl Environ Microbiol 46(1):293–295

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexander Scholz .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Scholz, A., Cerff, M., Posten, C. (2014). In Situ Magnetic Separation on Pilot Scale: A Tool for Process Optimization. In: Nirschl, H., Keller, K. (eds) Upscaling of Bio-Nano-Processes. Lecture Notes in Bioengineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43899-2_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-43899-2_11

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-43898-5

  • Online ISBN: 978-3-662-43899-2

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics