• Login
    View Item 
    •   DSpace@RPI Home
    • Rensselaer Libraries
    • RPI Theses Online (Complete)
    • View Item
    •   DSpace@RPI Home
    • Rensselaer Libraries
    • RPI Theses Online (Complete)
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Predictive scale-up of ion exchange chromatography using high throughput miniature columns

    Author
    Keller, William R.
    View/Open
    178265_Keller_rpi_0185E_10808.pdf (9.047Mb)
    Other Contributors
    Cramer, Steven M.; Bequette, B. Wayne; Karande, Pankaj; Robbins, P. David; Evans, Steven T.; Sejergaard, Lars;
    Date Issued
    2015-12
    Subject
    Chemical engineering
    Degree
    PhD;
    Terms of Use
    This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.;
    Metadata
    Show full item record
    URI
    https://hdl.handle.net/20.500.13015/1971
    Abstract
    These findings presented in this thesis will help to support the industry trend towards increased usage of miniaturized chromatography columns as a scale-down model system combined with column simulations for downstream process development.; The biopharmaceutical industry is consistently evolving to create new platforms and methods to implement in purification processes. Miniaturized chromatography columns have the potential to innovate the development and characterization of these processes. Their lower material requirements, parallel operation, and implementation into robotic liquid handling systems for autonomous operation make them suitable for increasing the number of process parameters that can be evaluated and reducing experimental time in development. In addition to the growing interest in these advantages, there is a desire for the miniature columns to be implemented as scale-down models. There is, however, a lack of understanding with respect to this implementation due to differences associated with the use of miniature columns and robotic liquid handling systems as compared to traditional scale-down systems. In this thesis, the utility of these columns and systems are investigated using both experimental and theoretical methods.; A detailed comparison was carried out using both experimental data and column simulations for miniature and traditional benchtop columns. Appropriate translations to account for extracolumn system volume differences were developed and shown to result in comparability. A parameter estimation protocol was then implemented to obtain linear steric mass-action (SMA) isotherm and lumped mass transport parameters from gradient experiments in both systems. The parameters estimated from the miniature columns were successfully employed to simulate the benchtop experimental data.; Column simulations were then employed to help understand the effects of system differences between operational formats. Step elution experiments were then designed in silico using the simulator to evaluate its potential for process development. The identified conditions were then carried out experimentally and simulation comparisons were employed to demonstrate that increased dispersion of the induced salt step changes in the benchtop system could help to explain the observed differences. These results showed that not only can the simulations be used to provide insight regarding the data differences observed between the two experimental formats, but they can also successfully account for the subtle differences in operation. These findings further support the use of miniature chromatography columns as a scale-down model system combined with column simulations for downstream process development.; A comparison was also carried out using both experimental data and column simulations for small scale RoboColumns®, using a robotic liquid handling system, and lab scale chromatography columns, using the traditional benchtop system. Importantly, the parameters obtained from the RoboColumn® experiments were shown to successfully predict the scaled-up behavior of the lab scale system.;
    Description
    December 2015; School of Engineering
    Department
    Dept. of Chemical and Biological Engineering;
    Publisher
    Rensselaer Polytechnic Institute, Troy, NY
    Relationships
    Rensselaer Theses and Dissertations Online Collection;
    Access
    Restricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.;
    Collections
    • RPI Theses Online (Complete)

    Browse

    All of DSpace@RPICommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login

    DSpace software copyright © 2002-2022  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV