ChromWorks software is capable of modeling, simulating, and analyzing nonlinear chromatography processes like simulated moving bed (SMB) separation. It uses techniques like Elution by Characteristic Points and dynamic estimation to determine nonlinear isotherm parameters from chromatogram data of single-column experiments. These isotherm parameters can then be used to simulate an SMB process in ChromWorks and analyze the tradeoff between throughput, purity, and desorbent consumption to determine optimal operating conditions. The software was successfully applied to two case studies - validating isotherm modeling for cycloketone separation and determining Langmuir isotherm parameters for enantiomer separation of amino acids.

1. Modeling, isotherm determination, and simulation of
nonlinear chromatography using ChromWorks software
Reid Erwin1
, Baochun Shen2
, Jay Yun3
, Yoshiaki Kawajiri1*
1. School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta,
GA 30332
2. School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural
Products, Kunming Medical University, Kunming, Yunnan, China
3. ChromWorks, 101 Middlesex Tpke, Ste. 6, Burlington, MA 01803
*
Corresponding author email: ykawajiri@chbe.gatech.edu
Modeling, simulation, and design of Simulated Moving Bed (SMB) chromatography pose many
challenges. Isotherm parameters must be obtained by analyzing chromatograms, which result in
a complex mathematical model. This mathematical model must be solved numerically to predict
and analyze the performance and process economics. Performing these tasks requires substantial
effort, and often multiple computational packages are used.
In this work, we employ ChromWorks, a computer-aided modeling and simulation software
package for preparative and continuous chromatography. This software is capable of performing
simulation, design, and analysis of various SMB processes, including isotherm parameter
estimation and determining optimal operating conditions by simulation. There are a number of
techniques implemented in ChromWorks. For isotherm determination, the Elution by
Characteristic Points (ECP) method provides an initial guess of nonlinear isotherm parameters
from multiple chromatograms of different injection volumes. This initial guess provides a good
starting point for dynamic estimation, where rigorous dynamic model is fitted to experimental
chromatograms to obtain isotherm parameters simultaneously with mass transfer and dispersion
coefficients. Isotherm data can then be transferred to the process design interface which utilizes
the triangle equilibrium diagram [1] to determine the optimal SMB operating conditions.
This study presents application of ChromWorks to the following two case studies of nonlinear
chromatography: (1) validation of isotherm modeling and finding operating conditions for SMB
separation of cycloketones (cyclopentanone, cyclohexanone) in Bentley et al. [2] and (2)
determination of Langmuir isotherm parameters for enantiomer separation of amino acids
(phenylalanines). The nonlinear isotherm parameters were obtained successfully from
chromatograms of single-column experiments. Furthermore, to design an SMB process, the

2. trade-off of throughput maximization and desorbent minimization while achieving purity
requirements was analyzed using the obtained model.
References
[1] Bentley, J., Sloan, C., & Kawajiri, Y. (2013). Simultaneous modeling and optimization of
nonlinear simulated moving bed chromatography by the prediction – correction method.
Journal of Chromatography A, 1280, 51–63.
[2] Mazzotti, M., Storti, G., & Morbidelli, M. (1997). Optimal operation of simulated
moving bed units for nonlinear chromatographic separations. Journal of Chromatography
A, 769, 3-27.