Microfluidics as a high-throughput solution for chromatographic process development - The complexity of multimodal chromatography used as a proof of concept

J Chromatogr A. 2021 Nov 22:1658:462618. doi: 10.1016/j.chroma.2021.462618. Epub 2021 Oct 8.

Abstract

High-throughput technologies are fundamental to expedite the implementation of novel purification platforms. The possibility of performing process development within short periods of time while saving consumables and biological material are prime features for any high-throughput screening device. In this work, a microfluidic device is evaluated as high-throughput solution for a complete study of chromatographic operation conditions on ten different multimodal resins. The potential of this class of purification solutions is generally hindered by its complexity. Taking this into consideration, the microfluidic platform was herein applied and assessed as a tool for high-throughput applications. The commercially available multimodal ligands were studied for the binding of three antibody-based biomolecules (polyclonal mixture of whole antibodies, Fab and Fc fragments) at different pH and salt conditions, in a total of 450 experiments. The results obtained with the microfluidic device were comparable to a standard 96-well filtering microplate high-throughput tool. Additionally, five of the ten multimodal ligands tested were packed into a bench-scale column to perform a final validation of the microfluidic results obtained. All the data acquired in this work using different screening protocols corroborate each other, showing that microfluidic chromatography is a valuable tool for the fast implementation of a new purification step, particularly, if the goal is to narrow the downstream possibilities by being a first point of decision.

Keywords: Antibody derivatives; High-throughput process development; Microfluidics; Multimodal chromatography.

MeSH terms

  • Chromatography*
  • High-Throughput Screening Assays
  • Ligands
  • Microfluidics*

Substances

  • Ligands