Tingyue Gu's Chromatography Simulation Home Page

(Chromulator Version 1.1 and Version 2.0)

Chromulator (Chromatography Simulator) has been licensed by chemical, pharmaceutical, and biotechnology companies such as 3M, AmeriChem, Pfizer, Wyeth BioPharma, Novo Nordisk, Chiron, Millipore, Nippon Rensui, Johnson Matthey of UK, IDEC Pharmaceutical, Schering Plough Research Institute. It is used in product development and manufacturing with proven results. I got comments like "Your model saves us a lot of experimental time and increases our R&D productivity tremendously." Chromulator has also been licensed by a large number of academic institutions in over a dozen countries. Chromulator V. 2.0 can be conveniently used to study the effects of various parameters in liquid chromatography by overlapping two sets of chromatograms. Free mass transfer parameter estimation utilities (Excel spreadsheet and soon-to-be released Windows version) are available upon request. Chromulator-IEX, a dedicated ion-exchange simulator for simple as well as complicated ion-exchange operations will be released in the coming weeks.  Dr. Tingyue Gu has in-depth knowledge in the dynamics of liquid chromatography as well as industrial experience in the bioseparations area. He is available for consulting jobs dealing with the development of chromatography media and operations, trouble-shooting and validation of existing systems, etc.  

This web page discusses the use and distribution of the chromatography software covered in the book entitled "Mathematical Modeling and Scale-up of Liquid Chromatography"  (Corrections are here) by Tingyue Gu, Springer Verlag, Berlin-New York, 1995. The book is currently out of print. The publisher will start printing again only when they accumulate enough back orders. All the Fortran codes described in the book are now available in the form of MS-DOS or Windows executables (.EXE files). They no longer use IMSL. I adopted a public domain ODE solver (with permission from its authors) from http://www.netlib.org/. Chromulator executables are distributed as free software to academic users for noncommercial applications. Commercial applications require a fee (see below). 

Chromulator v. 1.1 and v. 2.0  run much faster than their predecessors. For example, RATE.EXE is now 3-4 times faster than version 1.0. The minimum hardware requirement for Chromulator is a Pentium PC. Chromulator runs on today's PII, PIII and P4 computers very fast for chromatograms that are not extremely stiff.

The RATE.EXE demo package is a limited version of RATE.EXE. You will not be able to change the preset values of PeL=500, eta=5, Bi=5 and tmax=5. Otherwise, this RATE.EXE is fully functional. It is very easy to run RATE.EXE. Type rate.exe and the calculation will start. Type rate.exe > output.txt to run and save the results to output.txt file. The new Chromulator version 2.0 is even more convenient. Input and output are both on the screen. 

Downloadable demo packages 

The following papers contain useful information on the evaluation of parameters for the models:
1. T. Gu, K.-H. Hsu and M.-J. Syu, “Scale-Up of Affinity Chromatography for Purification of Enzymes and Other Proteins,” Enzyme and Microbial Technology, 33, 433-437 (2003) (PDF file, user=guest, password=guest) 
2. Z. Li, Y. Gu and T. Gu, "Mathematical Modeling and Scale-Up of Size Exclusion Chromatography." Biochemical Engineering J., 2, 145-155 (1998). (PDF file, 308KB, user=guest, password=guest)
3. T. Gu and Y. Zheng, "A Study of Scale-Up of Reversed-Phase Liquid Chromatography." Separation and Purification Technology, 15, 41-58 (1999). (PDF file, 954 KB, user=guest, password=guest)

The figure on the left below (from Li et al., 1998) shows an example of a priori prediction in low-pressure preparative size exclusion chromatography. The figure below on the right  (from Gu et al, 2003) shows an example for low-pressure preparative affinity chromatography. The solid and dashed lines in the figure are a priori predictions from AFFINITY simulator. The loading, washing and elution stages are predicted by simulation accurately. Chromulator seems well suited for the simulation of low pressure columns with considerable mass transfer effects.
 

The example below (from Gu and Zheng, 1999) is for reverse-phase gradient elution of human growth hormone and its analog on a C4 high pressure preparative column.

Experimental chromatogram and predicted dimensionless concentration profiles are compared in the figures below for gradient elution of four proteins using hydrophobic interaction chromatography (high pressure) (Truei, Y.-H., Gu, T., G.-J. Tsai, and G. T. Tsao, "Large-Scale Gradient Elution Chromatography," in Advances in Biochemical Engineering/Biotechnology, Vol. 47, Springer-Verlag, New York, 1992) (PDF file, user=guest, password=guest).


The following packages are available:


This simulator can be used to simulate isocratic elution using Langmuir isotherm or the ion-exchange type stoichiometic isotherm. Step change in mobile phase is also allowed. Mobile phase can contain a modifier. Displacement can use a reversed flow direction.
 
 


Instead of using Langmuir isotherm, the second-order kinetics is used. This simulator can also be used to simulate size-exclusion chromatography.
 


This simulator can be used to simulate gradient elution. It uses the eluite-modulator relationship proposed by Melander, et. al. Different kinds of gradient can be used: Linear, nonlinear or stepwise.
 
 


This software simulates the three stages (loading, wash and elution) in affinity chromatography. Elution can use an inhibitor.
 
 


This is the same as Rate.exe, except that it is for Radial Flow Chromatography (RFC).

It is beneficial for the understanding of the software if read my chromatography modeling book or my publications dealing with chromatography modeling. The software source codes can be modified to accommodate different initial concentration conditions inside the column, different feed profiles at the column inlet and different isotherms. Here is a document (in Adobe Acrobat format) explaining how to change the Fortran source code RATE.FOR for Rate.exe. All the source codes can be modified (by adding a few print statements) to output concentration profiles inside the column which show the peak migration patterns. The figure below shows the concentration profiles inside the column bulk-fluid phase. It corresponds to the simulated chromatogram at the top of this web page. The faster peak (component 1) has larger peak areas because it has fewer molecules absorbed in the stationary phase compared to component 1. The downloadable demo package (Windows version 1.1) above contains the simulator that was used for the figure.

 

For commercial uses, a license fee is required. Researchers from commercial companies are not eligible for free software. Academic users wishing to obtain source codes in addition to free executables will be treated as commercial buyers. However, discounts may be offered through negotiations.

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*** Copyright Agreement for Chromulator Version 2.x Software (Academic Version)***

1. The user agrees not to release the software to anyone outside his/her research group, and further agrees not to use the software for commercial purposes without paying a licensing fee.

2. The user agrees to mention that the software was developed by Tingyue Gu in publications produced with the help of the software. The software is provided "AS IS," and the author makes no warranties, expressed or implied.

 ********** End of Copyright Agreement **********

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(A graduate student cannot request the software. His/her advisor must sign the copyright agreement.)

Please e-mail the Copyright Agreement to . You can also send it via airmail to:
Professor Tingyue Gu
Department of Chemical Engineering
Ohio University
Athens, Ohio 45701, USA.
740-593-1499
 

Thank you for your interest.

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