Pre-packed MediaScout MiniChrom columns of 2.5, 5 and 10 mL were investigated for screening three mixed-mode chromatography sorbents (HEA, PPA and MEP HyperCel). Packing performance was of good quality and the three sorbents displayed higher capacity than traditional HIC sorbents in physiological-like conditions. Each sorbent offered a unique selectivity. Bovine beta-lactoglobulin was partially purified after loading milk whey directly on HEA HyperCel sorbent. The combination of small pre-packed columns and SELDI-MS appeared to be a valuable strategy for high-throughput screening of chromatography sorbents and for enabling rapid process development and optimization.