Using a box instead of a column for process chromatography

Columns with relatively short bed-height to diameter ratios are frequently used for process-scale chromatography applications such as biopharmaceutical purification. Non-uniform flow distribution within such columns could result in broad and poorly resolved eluted peaks, which could in turn affect purity, recovery and productivity of the process. Different strategies centered on improved column header design have been proposed for addressing this problem. This paper describes a radically different approach, i.e. the use of a chromatography box (or chromato-box) instead of a column, for addressing the challenges posed by flow mal-distribution in process-scale, packed-bed chromatography devices. The design of the chromatography box devices used in this study is based on a laterally-fed membrane chromatography (or LFMC) device, that has been described and discussed in several recent papers. The performances of two chromatography box devices were compared with their equivalent columns in terms of sharpness and asymmetry of flow-through and eluted peaks, number of theoretical plates per metre, and peak resolution in binary and ternary protein separations. In each of the above comparisons, the chromatography box devices performed better than their equivalent columns, clearly indicating their potential as an alternative in process-scale chromatography applications.