High Throughput Screening of Chromatographic Phases for Rapid Process Development

Abstract

The necessity of being ªfirst on the marketº paired with the need to cut production costs highlights the need for strategies and techniques allowing a fast process development while at the same time covering a high number of potential process parameters in order to reach an optimal process sequence. This can only be met by the use of high throughput screening (HTS) techniques. In this paper HTS applications presently applied in bioprocess development are reviewed, their use in chromatographic process parameter evaluation is discussed and concepts for the rational design of HTS experiments are presented. A rational approach for chromatographic parameter screening comprehends an initial screening procedure for ligand selection followed by the incorporation of specific adsorbent features using HTS pipetting systems finalized by a fine tuning step using packed mini-columns. The analytical part of these screening techniques clearly sets the bottleneck of these procedures with a trade off between analytical information and analysis time. Finally, intelligent HTS strategies should in addition include efficient data processing paired with modern tools for design of experiments or model based process design.

Recovery and purification process development for monoclonal antibody production

“…High throughput screening (HTS) in robotic format is being used to quickly optimize chromatographic separations. 71,72 This methodology can be used to optimize operating conditions for most types of chromatography, including affinity, ion-exchange, hydrophobic interaction and others. Resin selection, binding capacities, binding and elution conditions, impact of intermediate wash steps, yield, as well as resolution of impurities can be determined in automated fashion.…”

A novel magnetic bead‐based assay with high sensitivity and selectivity for analysis of telomerase in exfoliated cells from patients with bladder and colon cancer

“…The magnetic rods, which move the magnetic particles to specific locations containing appropriate reagents and wash solutions, are covered with disposable tips to prevent cross-contamination of samples. This instrument has previously been used for a number of applications including automated nucleic acid [62][63][64][65], protein and peptide [23,66,67], Escherichia coli [68] and beadbased luminescence assays [69].…”

Micro biochemical engineering to accelerate the design of industrial‐scale downstream processes for biopharmaceutical proteins

“…There have also been reports on adsorption by Welch et al (2002), Lye et al (2003), Kökpinar et al (2006) and the operation of linked process sequences (Ferreira-Torres et al, 2005). Bensch et al (2005) have used an automated microwell-based method to permit high throughput screening of chromatographic phases and in the same group Wierling et al (2007) have applied high throughput methods using SELDI-TOF-Mass spectrometry for chromatographic analysis. In a recent patent application a high throughput chromatographic screening approach is also described (US, 200754390).…”