A new general method for designing affinity chromatography processes

• Minimum column volume VCmin for Langmuir systems is found without simulations.
• Only material properties obtained from a few experiments are needed to find VCmin.
• Effects of material properties and design criteria on VCmin are found graphically.
• If a dimensionless loading time is 0.5 or larger, diffusion effects are negligible.
• Small loading time and relative diffusion time reduce VCmin and increase productivity.

Affinity chromatography is widely used for selectively recovering a target solute from a complex mixture. The challenge in designing a capture process is to achieve high yield, high column utilization, and high sorbent productivity while satisfying loading time and pressure limit requirements. The conventional design method based on constant-pattern waves cannot be used for small feed batches or short columns, which do not allow the formation of such waves. Other design methods in the literature rely on simulations or experimental trials, and can be time-consuming and costly. In this study, a new design method with no need of simulations is developed for constant pattern and non-constant pattern systems with Langmuir isotherms. Given feed conditions, loading time, and desired yield, the design requires only the values of certain intrinsic parameters, which can be estimated from a small number of bench-scale experiments. The minimum column volume for capture can be estimated either graphically or analytically. The method is tested with Protein A chromatography data for antibody purification. It is applicable to a wide range of production scales and design requirements. The effects of material properties, feed composition, feed volume, and design requirements on the column volume for capture can be found graphically. When the loading time relative to a characteristic diffusion time is 0.5 or larger, the minimum column volume approaches that of an ideal system. A short loading time increases sorbent productivity, but increases the minimum column volume. A high feed concentration, a high equilibrium capacity, and a small diffusion time relative to the loading time can reduce the minimum column volume and increase productivity.