TY - JOUR
T1 - Chromatographic parameter determination for complex biological feedstocks
AU - Pirrung, Silvia M.
AU - Parruca da Cruz, Diogo
AU - Hanke, Alexander T.
AU - Berends, Carmen
AU - Van Beckhoven, Ruud F.W.C.
AU - Eppink, Michel H.M.
AU - Ottens, Marcel
PY - 2018
Y1 - 2018
N2 - The application of mechanistic models for chromatography requires accurate model parameters. Especially for complex feedstocks such as a clarified cell harvest, this can still be an obstacle limiting the use of mechanistic models. Another commonly encountered obstacle is a limited amount of sample material and time to determine all needed parameters. Therefore, this study aimed at implementing an approach on a robotic liquid handling system that starts directly with a complex feedstock containing a monoclonal antibody. The approach was tested by comparing independent experimental data sets with predictions generated by the mechanistic model using all parameters determined in this study. An excellent agreement between prediction and experimental data was found verifying the approach. Thus, it can be concluded that RoboColumns with a bed volume of 200 μL can well be used to determine isotherm parameters for predictions of larger scale columns. Overall, this approach offers a new way to determine crucial model input parameters for mechanistic modelling of chromatography for complex biological feedstocks.
AB - The application of mechanistic models for chromatography requires accurate model parameters. Especially for complex feedstocks such as a clarified cell harvest, this can still be an obstacle limiting the use of mechanistic models. Another commonly encountered obstacle is a limited amount of sample material and time to determine all needed parameters. Therefore, this study aimed at implementing an approach on a robotic liquid handling system that starts directly with a complex feedstock containing a monoclonal antibody. The approach was tested by comparing independent experimental data sets with predictions generated by the mechanistic model using all parameters determined in this study. An excellent agreement between prediction and experimental data was found verifying the approach. Thus, it can be concluded that RoboColumns with a bed volume of 200 μL can well be used to determine isotherm parameters for predictions of larger scale columns. Overall, this approach offers a new way to determine crucial model input parameters for mechanistic modelling of chromatography for complex biological feedstocks.
KW - chromatography
KW - downstream processing (DSP)
KW - high-throughput process development (HTPD)
KW - mechanistic modeling
UR - http://resolver.tudelft.nl/uuid:cecae385-34a5-41ae-bf20-a58d77123ff9
UR - http://www.scopus.com/inward/record.url?scp=85050625674&partnerID=8YFLogxK
U2 - 10.1002/btpr.2642
DO - 10.1002/btpr.2642
M3 - Article
AN - SCOPUS:85050625674
SN - 8756-7938
VL - 34
SP - 1006
EP - 1018
JO - Biotechnology Progress
JF - Biotechnology Progress
IS - 4
ER -