Small, smaller, smallest: Miniaturization of chromatographic process development

Tiago Castanheira Silva, Michel Eppink, Marcel Ottens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)


Biopharmaceuticals are becoming increasingly important in modern healthcare. Monoclonal antibodies (mAb) are one of the most widely used therapeutic proteins and are important for the treatment of cancer and autoimmune diseases, among others. After cell culture there are still large amounts of other impurities (e.g. host cell proteins) in solution. Chromatography is usually the first purification step, allowing to increase purity and reduce volume. This comes associated with high costs and chromatography accounts for a significant portion of total production costs for therapeutic proteins. Chromatographic process development may be time consuming and use large amounts of resins. Therefore, there is increased interest in finding cheaper techniques for chromatographic process development without compromising accuracy. This paper presents a highly sophisticated microfluidic chip approach for efficient adsorption isotherm determinations compared to current chromatographic process development. Implementation of an image analysis software ensures that chromatographic resin volume is accurately determined. The adsorption isotherm performance of microfluidics was compared to the robotic Liquid-handling Station (LHS) and labor intensive Eppendorf tubes. The microfluidic chip allows a 15-fold volume reduction and resin consumptions as low as 100/200 nl (200/100-fold reduction). The microfluidic chip performed comparably to the other miniaturized techniques, using less liquid and resin volume. For process development of expensive products (e.g. monoclonal antibodies), miniaturization (provided by the microfluidic chip) proved to be the most cost effective alternative whereas for less valuable products (e.g. lysozyme) automation (provided by the LHS) was the most cost effective alternative.

Original languageEnglish
Article number463451
JournalJournal of Chromatography A
Publication statusPublished - 11 Oct 2022


  • Batch adsorption protein isotherms
  • High-Throughput Screening
  • Liquid-Handling Stations
  • Microfluidic chromatography
  • Miniaturization


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