Sampling, sample treatment, assay and real time monitoring of biotechnological processes using an integrated flow-injection system

Mohammad Mazlomi

Research output: ThesisDoctoral Thesis (monograph)

Abstract

Microorganisms can be used for production of pharmaceutical substances. With the
introduction of gene technology, it is possible to transfer information from one
organism to the other, thereby making the receiving organism capable of producing
substances that it did not so before. This development is very important for e.g.
production of therapeutic proteins
However, when using living organisms for production there is a need for controlling
a range of different parameters. In order to understand the process it is necessary
to have as much information as possible and then an algorithm to analyze the data.
In this thesis work is presented that addresses some of the bottlenecks in
development of process monitoring. The coaxial catheter was evaluated with regard
to sampling from complex, sensitive medium without leakage of the inhibitory
solution that is used for instantaneous stopping of ongoing enzymatic/microbial
processes in the sample.
An automated system for advanced flow injection analysis of complex
biotechnological processes has been constructed and it was used to evaluate
efficiency of different inducer combinations when expressing a clone of enzyme.
One key factor in flow injection analysis is to prevent flow problems. The
introduction of supermacroporous hydrogels made it possible to introduce whole
broth from a fermenter into the system and also to include a superporous
catalytically active gel composed of microbial cells directly cross-linked to each
other.
Even if there is a need, still very few successful examples are presented where
advanced monitoring is used to control the processes. The missing part here is the
lack of a reliable, representative and robust sampling and sample handling system,
which is compatible with analytical devices.
The objective of this thesis work was to develop an aseptic and representative
sampling unit and treatment of the bioreactor product in the flow system, and
finally, analysing the sample by enzymatic and immunoassays in the integrated flow
system.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Biotechnology
Supervisors/Advisors
  • Mattiasson, Bo, Supervisor
  • Hedström, Martin, Supervisor
Award date2011 Dec 15
ISBN (Print)978-91-89627-79-6
Publication statusPublished - 2011

Bibliographical note

Defence details

Date: 2011-12-15
Time: 10:30
Place: Lecture Hall B, Kemicentrum, Getingevägen 60, Lund University, Faculty of Engineering

External reviewer(s)

Name: Håkansson, Håkan
Title: Professor
Affiliation: GS Development, Malmö

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Subject classification (UKÄ)

  • Industrial Biotechnology

Keywords

  • Bioprocess
  • Sampling
  • Sample treatment
  • On-line monitoring
  • Real time monitoring
  • Flow injection
  • Immunoassay
  • Fermentation

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