Institut für Verfahrenstechnik, Umwelttechnik und Techn. Biowissenschaften
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Real-time characterisation of bioprocesses


Wir bitten um Verständnis, dass die Informationen über dieses Projekt derzeit nur in englischer Sprache verfügbar sind.


Project Content:

Quality by Design (QbD) is a current structured approach to design processes yielding a quality product. Design of Experiment (DoE) is employed to explore the multivariate interdependencies between process parameters (such as temperature, dissolved oxygen…), process information (such as specific rates and yields) and process quality attributes (such as product purity).

Process Analytical Technology (PAT) provides the tools to acquire to data which are used to acquire information on the process, such as yields, rates and time constants and their physiological adaption over time. One gap in PAT is the lack of well established methods for on-line determination of biomass, as this represents an impediment for the calculation of an on-line growth rate and specific rates of metabolites and substrates.

In the current project available methods such as capacitance, fluorescence or indirect estimation by soft-sensors are investigated for its suitability to calculate specific rates along with a procedure for error testing and reconciliation of data in real-time. Microbial cultures are used as model systems and experiments are conducted in scales ranging from 1 to 20L.

The project aims at establishing and validating a general methodology to characterize strains in real-time, generating error checked and consistent yields and rates, which are essential for scientifically based process understanding.


  1. Sonnleitner, B. and Kaeppeli, O., 1986. Growth of Saccharomyces cerevisiae is controlled by its limited respiratory capacity: formulation and verification of a hypothesis. Biotechnol. Bioeng. 28(6), 927-937.
  2. Herwig, C., Marison, I., Von Stockar, U., 2001. On-line stoichiometry and identification of metabolic state under dynamic process conditions. Biotechnol. Bioeng. 75(3), 345-354.
  3. Wang, N.S. and Stephanopoulos, G., 1983. Application of macroscopic balances to the identification of gross measurement errors. Biotechnol. Bioeng. 25, 2177-2208.
  4. van der Heijden, R.T.J.M., Romein, B., Heijnen, J.J., Hellinga, C., Luyben, K.C.A.M., 1994a. Linear constraint relations in biochemical reaction systems: III. Sequential application of data reconciliation for sensitive detection of systematic errors. Biotechnol. Bioeng. 44, 781-791.


Industrial Partner:

Biopharmacutical Contract Manufacture


Scientific contributions:


  1. Wechselberger, P., Seifert, A., Herwig, C., 2009. PAT-Method to gather real-time bioprocess understanding using simple on-line signals and first principle relationships. Chem. Eng. Sc.
  2. Wechselberger, P., Herwig, C., 2011. Model-based analysis on the relationship of signal quality to real-time extraction of information in bioprocesses. Biotechnology Progress submitted.



Univ.Prof. Dipl.-Ing. Dr.techn. Christoph Herwig


Patrick Wechselberger