High Throughput Screening for the Design and Optimization of Chromatographic Processes: Assessment of Model Parameter Determination from High Throughput Compatible Data

Abstract

Chromatographic processes can be optimized in various ways, and the two most prominent approaches are based either on statistical data analysis or on experimentally validated simulation models. Both strategies rely heavily on experimental data, the generation of which usually imposes a significant bottleneck on rational process design. The latter approach is followed in this work, and the utilizability of high throughput compatible experiments for the determination of model parameters which are required for in silico process optimization, is assessed. The unknown parameter values are estimated from batch uptake experiments on a robotic platform and from dynamic breakthrough experiments with miniaturized chromatographic columns. The identified model is then validated with respect to process optimization by comparison of model predictions with experimental data from a preparative scale column. In this study, a strong cation exchanger Toyopearl SP-650M and lysozyme solved in phosphate buffer (pH 7), is used as the test system. The utilization of data from miniaturized and high throughput compatible experiments is shown to yield sufficiently accurate results, and minimizes efforts and costs for both parameter estimation and model validation.

Employee Readiness for Organizational Change: A Case Study in an Export Oriented Manufacturing Firm in Sri Lanka

“…Susanto (2008) highlights the importance of having better judgment on individual change readiness perception prior to any change implementation. A good assessment of employee change readiness would help change agents, business consultants and management to understand the gap between their own expectation about the change and the change recipients' anticipation of the change (Ghany, 2014).…”

Therapeutic plasma proteins – application of proteomics in process optimization, validation, and analysis of the final product

“…Optimizations of preparative chromatographic processes are frequently based on experimentally validated simulation models. This strategy requires a large amount of experimental data, and their generation imposes a significant bottleneck on rational process design [30]. Susanto et al [30], Charlton et al [31], and Coffman et al [32] have demonstrated that high-throughput screening can be a rapid way to acquire these data.…”

“…This strategy requires a large amount of experimental data, and their generation imposes a significant bottleneck on rational process design [30]. Susanto et al [30], Charlton et al [31], and Coffman et al [32] have demonstrated that high-throughput screening can be a rapid way to acquire these data. Those studies used different columns with bed volumes between 0.1 and 1 mL that were installed into a 96-well microplate.…”

A label‐free methodology for selective protein quantification by means of absorption measurements

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“…From column experiments, information on dynamic binding capacities and chromatographic resolution can be derived. Both batch and column chromatography in HTE mode can also be used to determine parameters for mechanistic modeling of chromatographic processes (Susanto et al, 2008).…”