Institut für Verfahrenstechnik, Umwelttechnik und Techn. Biowissenschaften
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Online monitoring devices for efficient bioprocess quantification


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


Project Content:

During the last decades enhanced efforts were carried out to develop novel online monitoring devices for fast and reliable process monitoring in bioprocesses. The goal of the project aims to establish and characterize several novel devices for their online applicability and potential for robust real time data determination which can be consequently used within Process Analytical Technology approaches.

Enzymatic photometric robot:

A novel enzymatic photometric robot with the potential to measure a multitude of substrates and other components in parallel was connected to a fully equipped bioreactor set up. After characterization several batch cultivations were carried out to validate the online determined data in comparison to offline values. The system was successfully used to identify several limitation events and the physiological response evaluated based on online rates and yields were computed out of the determined data.

Figure 1 Physiological response of P. pastoris on a nitrogen limitation event.

Online HPLC:

HPLC (high performance liquid chromatography) is a robust and precise standard analytical technique both for the quantification of small and large molecules. The wide application spectrum and the possibility of simultaneous measurement of multiple components in a short time qualify HPLC for use as bioprocess analytical tool.

Aiming at automated, real-time extraction of chemical information from bioprocesses, an on-line HPLC device (Thermo Fisher,     Waltham, Massachusetts, USA) equipped with refractive index (RI) and Photodiode Array (PDA) detectors was interfaced with a bioreactor. Cell-free samples are sampled using ceramic, 0.2 µm filtration devices (IBA, Heiligenstadt, Germany) and pumped to a flow cell integrated in the HPLC setup (see figure 2). In predefined intervals, the HPLC automatically samples, analyzes, and integrates, resulting in the real-time quantification of different analytes.

The real-time chemical data can be used for a) the extraction of high quality information for fast and efficient bioprocess development and b) the development of bioprocess control strategies.

Current challenges

  1. Integration of on-line HPLC in (soft-sensor assisted) bioprocess control strategies
  2. Real-time quantification of product quantity and product quality


Figure 2 Online HPLC (left) connected via a peristaltic pump (center) to a pilot scale bioreactor (right).


Figure 3: Real-time high resolution data of glucose concentration and acetate concentration of an E. coli batch process measured via on-line HPLC.

Scientific contributions:


Dietzsch, C., Spadiut, O., Herwig, C., (2012) On-line multiple component analysis for efficient quantitative bioprocess development. Journal of biotechnology accepeted. DOI: 10.1016/j.jbiotec.2012.03.010

Spadiut O, Dietzsch C, Posch A, Herwig C: Evaluating online sampling probes for substrate concentration and protein production by a Design of Experiments screening approach. Engineering in life Sciences 2012, 12:507-513.



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


Christian Dietzsch

Univ.Ass. Dipl.-Ing. Dr.nat.techn. Oliver Spadiut

Patrick Sagmeister