A systematic approach to improve data quality in high-throughput batch adsorption experiments

High-throughput process development (HTPD) techniques are routinely used for making initial screening decisions, scaling up unit operations, and developing models for unit operations. With increased pressure to deliver candidate molecules to the clinic, HTPD approaches have become a necessity. Because of this increased reliance on HTPD methods, the fidelity of the data is of critical importance. Improving the robustness of each HTPD technique requires a systematic consideration of each step involved. In this work, multiple aspects of high-throughput chromatography adsorption isotherms are explored for improvement: chromatography resin slurry dispensing, experimental design, and experimental execution. Chromatography resin slurry dispensing techniques have been presented in the literature, but the present work utilizes a dry resin mass basis to correlate settled column volume with slurry volumes dispensed via a liquid handler. In addition, a new graphical procedure is presented to determine optimal conditions for adsorption isotherm experiments where only an initial estimate of the maximum binding capacity is required. The final component of experimental optimization will be explored with examples of how careful scrutiny of multiple steps is required for robust data collection. The impact of these efforts vis-a-vis predictability of process conditions such as dynamic binding capacity is also explored.