Process Design Space
High‐throughput chromatographic method development becomes increasingly important as the bioprocess industry works to meet the challenges posed by the Quality by Design (QbD) initiative. A common approach is parallel batch adsorption experiments in filter microplate format where 5 to 20 μL of a resin slurry is transferred into the wells, incubated with feedstream samples and separated by vacuum or centrifugation. Traditional equilibrium binding, washing and elution steps are performed and assayed for product and impurities. This approach is relatively complex to automate, has multiple wash and elution steps that can lead to poor yield and reproducibility and cannot be used to observe dynamic binding capacity and other non-equilibrium separation effects. The other major approach is to use small columns operated in parallel on a standard robotic liquid handler. Because these columns are typically 5 mm in diameter, bed volumes below 200 μL are not very practical, which means that a significant volume of feedstream is needed to perform some experiments.
With a 5 μL bed volume of AssayMAP cartridges, precise flow rates down to 1 μL per minute or less is required to achieve residence times appropriate for process chromatography. This is accomplished using patent‐pending “probe syringe” technology where pistons in a multi‐channel liquid handling head have been replaced with ultra‐low dead volume syringes equipped with a special probe. Mounting a cartridge to the probe provides a direct fluid connection between the top of the bed and the interior of the syringe through the cartridge inlet seal that enables precise, positive displacement pumping in both directions through the bed. Currently a 12‐ channel workstation is offered; a 96‐channel version is under development.
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