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Development of a 3D printed micro simulated moving bed chromatography system.

Juliane Diehm1, Tim Ballweg1, Matthias Franzreb1

  • 1Institute of Functional Interfaces, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen 76344, Germany.

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Researchers developed a micro simulated moving bed chromatography (µSMB) system, the smallest ever built. This innovative system achieves high purity and yield for protein purification, offering a valuable tool for process development and specialty product manufacturing.

Keywords:
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Area of Science:

  • Chemical Engineering
  • Analytical Chemistry
  • Biotechnology

Background:

  • Simulated moving bed (SMB) chromatography, invented in the 1960s, significantly improved separation performance, resin utilization, and reduced buffer consumption compared to batch chromatography.
  • Despite its industrial success, SMB chromatography has not been adapted for micro-scale applications (column and system volumes).

Purpose of the Study:

  • To implement and evaluate a micro simulated moving bed chromatography (µSMB) system for small-scale separation tasks.
  • To demonstrate the utility of µSMB for applications such as early process development, long-term studies, and downstream processing of specialty products.

Main Methods:

  • A µSMB system was constructed featuring a 3D-printed central rotary valve and a microfluidic flow controller.
  • The system was tested using a four-zone, open-loop configuration for the size exclusion chromatography of bovine serum albumin (BSA) and ammonium sulfate.
  • Experiments were conducted with varying process points to assess desalting efficiency and yield.

Main Results:

  • The µSMB system achieved desalting levels of BSA ranging from 94% to 99%, with corresponding yields between 65% and 88%.
  • The system demonstrated comparable results to conventional lab-scale processes.
  • The total dead volume of the system, including sensors, connections, and the valve, was measured at 358 µL, representing the smallest SMB system reported to date.
  • The system successfully performed experiments with feed flow rates as low as 15 µL/min.

Conclusions:

  • The developed µSMB system is the smallest SMB system ever constructed, offering a powerful tool for micro-scale chromatographic separations.
  • The system effectively purifies biomolecules like BSA, achieving high purity and yield, comparable to larger-scale methods.
  • This micro-scale SMB technology holds significant potential for various applications in bioprocess development and specialty chemical manufacturing.