Biotechnological processes

Industrial biotechnology is a key technology for the development of a sustainable chemical industry and especially for the bioeconomy.

Your challenges

Transferring a biotechnological process from the laboratory to industrial scale not only requires specific expertise, but also the appropriate plant technology in order to successfully cope with the scale-up. Numerous parameters must be taken into account in order to guarantee the desired product quality while keeping the operating costs of the process as low as possible. Downstream processing is particularly crucial for the economic efficiency of a fermentation process in order to achieve efficient separation of the products.

Our unique selling point: pilot plants and expertise in scaling biotechnological conversion processes

While academic research laboratories are widespread, pilot plants are still rarely found. Yet they are urgently needed, especially for smaller companies, to prepare innovations for the commercialization of new products. In addition to the technical advancement of biotechnological processes, the provision of larger quantities of material for application research as well as process data for economic and other studies on the feasibility of a manufacturing process are of particular importance. We rely on our comprehensive bioprocess engineering expertise in scaling and process intensification and our many years of experience in this field when transferring manufacturing processes (precision fermentation, enzyme synthesis) to an industrial scale.

Range of services

The team possesses broad bioprocess engineering expertise in the field of scale-up and process intensification. The processes developed on the laboratory scale are evaluated in the preliminary stages in terms of their transferability to industrially relevant equipment at scale and are optimized repetitively during transfer and scale-up. This includes, for example, the adjustment of process control strategies (batch, fed-batch, continuous) and integrated product purification to reduce the number of process steps or the reutilization of the deployed resources, e.g. by immobilization of biocatalysts on carrier materials.

 

Services offer at a glance

  • Fermentative or enzyme-catalyzed production of various products
  • Evaluation, development, and optimization of biotechnological processes
  • Scale-up to pilot and demonstration scale 
  • Establishment of downstream processing strategies for fermentations and enzyme reactions
  • Utilization of alternative carbon sources in fermentation (e.g., lignocellulose hydrolysates or methanol)
  • Preparation of sample quantities (along the kilogram to ton scale)
Fermentation am Fraunhofer CBP
© Norbert Michalke / Fraunhofer IGB
Bioreactor cascade for scaling fermentation processes

Broad product portfolio: bulk and fine chemicals, proteins, monomers for plastics

In Industrial Biotechnology at Fraunhofer CBP, we focus on the material use of renewable raw materials through the fermentative or enzymatic synthesis of bio-based chemicals and the recombinant production of proteins and enzymes for various areas of application. We develop and scale precision fermentations on behalf of customers from a wide range of industries, for example in the areas of basic and bulk or specialty chemicals (e.g., dyes or monomers for materials and plastics) as well as food, dietary supplements, and animal feed. One special application is the scaling of fermentations for the production of alternative proteins.

 

Product portfolio at a glance

  • Milk proteins and other food substitutes and additives
  • Organic acids (e.g., itaconic acid) and solvents (e.g., butanol)
  • Bulk and specialty chemicals (e.g., dyes)
  • Technical and other enzymes
  • High-protein biomass

Collaboration

Since more than ten years, the Bioprocess Scale-up group at Fraunhofer CBP in Leuna is making a significant contribution to the introduction of new biotechnological processes in industry. 

Partner of start-ups and SMEs for optimizing and scaling up biotechnological processes

In particular, we support start-ups as well as small and medium-sized enterprises in Germany, Europe and from all over the world in the implementation of their projects by providing equipment and know-how for the scaling and optimization of fermentation processes and the associated downstream processes.

How to work with us

You can contract us directly to develop, optimize, or scale a fermentation process. We would be happy to show you our facilities and equipment options during an initial consultation. Some issues can also be investigated within publicly funded projects, e.g., as part of bioeconomy programs. We are looking forward to cooperating with other entrepreneurs and scientists, please feel free to approach us with your ideas or challenges to explore solutions together!

Equipment

The equipment in the area of bioprocess scale-up comprises two modularly constructed pilot plant halls of biological safety level 1. Thanks to our automated, sterile pilot plants for scaling and optimizing fermentation processes up to 10 m3 and the associated downstream processes, we can produce sample quantities ranging from kilograms to tons.

Cultivation of microorganisms and fermentation

Microorganisms in risk group 1 (BSL 1) can be cultivated under aerobic and anaerobic conditions. Furthermore, the fermentation processes can be operated in different regimes (batch, fed-batch, continuous).

 

Automated bioreactor cascade with comprehensive measurement and control technology for fermentation of various microorganisms

  • Bioreactors of 10 / 100 / 300 / 1,000/ 10,000 L (gross volume)
  • Geometrically similar and fully automated
  • Measuring/control technology for stirrer speed, temperature, headspace pressure, pH value, dissolved oxygen, methanol concentration, and exhaust gas analysis (CO2/O2)
  • In-situ sterilization (SIP) and cleaning (CIP)
  • Equipped with four stainless steel storage tanks each for acid, base, antifoam and feed
  • Automated methanol dosing
  • pH control by supply of gaseous ammonia in the 10 m3 bioreactor possible

 

ATEX fermenter

  • 500 L gross volume
  • For conversion or production of highly flammable chemicals

 

Ultra-high temperature (UHT) system for continuous media sterilization

  • 1 – 2 m³/h
  • 60 – 134°C
  • 120 – 240 s holding time

Product purification and finishing

Storage tanks for harvest of fermentation suspensions or temporary storage of product solutions

  • 2 x 500 L (mobile), 2 x 2,000 L, 2 x 5,000 L, 2 x 10,000 L (gross volume)
  • Stirred
  • pH- and temperature-controlled

 

Biomass separation technology

  • Disc stack separators
    • 0.5–1 m³/h (12,300 x g)
    • 1–2 m³/h (12,800 x g)
  • Filter press
    • 10 filter plates with 0.4 m² filter area each and 5 L working volume
  • Vacuum drum filter 
    • 0.5 m² filter area
  • Vacuum filter dryer
    • 0.5 m² filter area (cut-off: 1 and 10 µm)
    • 400 L working volume
    • ATEX-compliant

 

Cell disruption

  • High-pressure homogenizer
    • 400 L/h, 1,000 bar
    • Flow cooling possible

 

Fine purification

  • Membrane filtration (cross-flow micro-/ultra filtration)  for desalination and product concentration processes
    • Feeding up to 500 kg/h
    • Flexible use of spiral wound modules (material, cut-off)
  • Liquid chromatography
    • 7–35 L column volume
    • Pump power up to 180 L/h
  • Crystallizers (batch)
    • 180 L mobile
    • 800 L in ATEX-compliant version
    • Temperature-controlled

 

Product finishing 

  • Spray dryer
    • up to 5 kg/h (140–300°C)
  • Freeze dryer
    • 0.9 m2 (15 L working volume)
Plate separator for separating microorganisms from the culture medium
© Fraunhofer CBP
Plate separator for separating microorganisms from the culture medium
Cell disruption: To make valuable products available in microorganisms, a high-pressure homogenizer can be used.
© Fraunhofer CBP
Cell disruption: To make valuable products available in microorganisms, a high-pressure homogenizer can be used.
Spray dryer
© Fraunhofer CBP
Spray dryer

Analytical equipment

HPLC
© Fraunhofer CBP
HPLC
  • Photometric analysis (e.g., optical density, enzyme activity)
  • Determination of organic dry matter
  • YSI 2950 (biochemical analyzer), e.g. for determination of sugars
  • HPLC-DAD, HPLC-VWD, HPLC-RID, HPLC-SEC, e.g. for determination of sugars, organic acids, phenolic compounds 
  • Headspace-GC, GC-MS, GC-FID and GC-TCD
  • Anion exchange chromatography
  • Thin-layer chromatography
  • Protein analysis (e.g., SDS-PAGE, Bradford, Lowry)
  • UV/VIS spectrophotometer for microtiter plates and cuvettes
  • Infrared spectrometer

References