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Extreme Scale-Down Approaches for Rapid Chromatography Column Design and Scale-Up During Bioprocess Development

Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE,volume 132)

Abstract

Chromatography is a ubiquitous protein purification step owing to its unparalleled ability to recover and purify molecules from highly complex industrial feedstocks. Traditionally, column development has been driven by a combination of prior experience and empirical studies in order to make the best choices for design variables. Economic constraints now demand that companies engage with a more systematic exploration of a chromatographic design space. To deliver this capability using purely conventional laboratory columns, however, would require considerable resources to identify practical and economical operating protocols. Hence, recently there has been increased use of extremely small-scale devices that gather data quickly and with minimal feed requirements. Such information can be obtained either during early development for screening and trend-finding purposes or later for more accurate scale-up prediction. This chapter describes some of the key drivers for these small-scale studies and the different types of extreme scale-down chromatography formats that exist and illustrates their use through published case studies. Since extreme scale-down experimentation is linked to fundamental mechanistic engineering approaches as well, the utility of these in delivering process understanding is also highlighted.

Graphical Abstract

Keywords

  • Batch incubation
  • Extreme scale-down
  • High-throughput screening
  • Miniature columns
  • Pipette tips

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  • DOI: 10.1007/10_2012_174
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Correspondence to Sunil Chhatre .

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Chhatre, S. (2012). Extreme Scale-Down Approaches for Rapid Chromatography Column Design and Scale-Up During Bioprocess Development. In: Mandenius, CF., Titchener-Hooker, N. (eds) Measurement, Monitoring, Modelling and Control of Bioprocesses. Advances in Biochemical Engineering/Biotechnology, vol 132. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2012_174

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