One of the key questions in chromatographic bioprocessing is “how does one identify the most selective resin for a given separation challenge?” This question can be quite complex in practice since purification typically begins from a crude cell culture fluid (CCF) as opposed to a well-defined mixture of specific proteins. This complexity is further multiplied since overall purification performance is determined by selectivity in several solution conditions (load, wash, and eluent). In order to address this challenge, we have investigated new ways of carrying out 96-well plate batch resin screening experiments. By coupling “isotherm-like” adsorption experiments (single component and in the presence of CCF) with a UPLC-based assay for product and impurity detection, we are able to strategically generate parts of the competitive adsorption isotherms which can clearly distinguish affinity, pseudo affinity and single mode interaction type behavior. When used in conjunction with automated liquid handling systems, this methodology provides a powerful tool for the high throughput screening of resins with potential applications in resin design, resin selection, and process development.

Targeted, high-throughput assessment of the selectivity of chromatographic resins

251st National Meeting (2016)

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