Bioprocess scale-up

We have a broad bioprocess engineering know-how for process intensification and scale-up, whereby the processes developed on a laboratory scale are evaluated in advance with regard to their transferability to the industrial relevant scale and optimized iteratively during transfer and scale-up. These include the adaptation of process control strategies (batch, fed-batch, continuous) and integrated product purification to reduce process steps or the reuse of biocatalysts (e.g. by immobilization on carrier materials). In addition to the scale-up of processes to demonstration scale, we also provide sample quantities for application tests.

Fields of activity and technologies

Enzyme production and biocatalysis

Together with our customers, we develop, optimize and/or scale up the production of enzymes up to pilot scale. The enzyme can be purified for biocatalysis or whole-cell catalysis can be carried out.

 

Fermentative production of carboxylic acids

We are developing new economical processes for the sustainable production of malic, xylon and itaconic acid from lignocellulosic sugars. We have successfully demonstrated the production of malic acid from xylose on a 1 m³ scale.

 

Reference: Process demonstration isobutene

A novel process for the production of isobutene developed by the company Global Bioenergies is based on the fermentative production of gaseous isobutene from sugars using genetically modified microorganisms. To scale up this process, we have built up and operated a demonstration plant with a nominal capacity of 100 tonnes per year and a fermentation volume of 5000 liters.

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.

The equipment in the area of biotechnological processes comprises two modularly constructed pilot plant halls of biological safety level 1, whereby one of the halls can be operated under ATEX conditions.

Equipment

The facilities include a central microbiological laboratory, two module-based technical centers of the Biosafety Level 1, one of which can be operated under ATEX conditions.

 

Cultivation

  • Fermentation of various microorganisms: reactor cascade with total volumes of 10, 100, 300, 1000 and 10,000 liters, equipped with four storage tanks each (acid, base, antifoaming agent, nutrition solution) as well as comprehensive automation, measurement and control technology (rotation speed, temperature, head space pressure, pH value, dissolved oxygen, respiration, methanol concentration)
  • UHT plant for the continuous sterilization of fermentation media
  • ATEX fermenter (total volume: 500 L) for conversion or production of highly flammable chemicals
  • Continuous process control in fermentations by cell retention (sterilizable crossflow filtration plant with automatic feed level control)
  • Online measurement of alcohol concentration in the reactor and of CO2/O2 in the fermentation exhaust gas


Enzymatic conversions 

  • Reactors for enzyme-catalyzed reactions (500 (mobile), 1300, 2000, 5000 and 10,000 liters, stirred, temperature-controlled)
  • Enzymatic hydrolysis / modification of fibers (tank with special stirrer configuration for high viscosities)


Product purifcation and finishing 

  • Harvest of the fermentation suspension as well as temporary storage of product solutions using stirred and temperature-controlled tanks (500 (mobile) / 2,000 / 5,000 and 10,000 L)
  • Biomass separation (disk separators 0.5 – 2 m3/h, 0.5 – 1 m3/h, vacuum drum cell flter 0.5 m2 and fiter press 1.6 m2)
  • Cell disruption (homogenizer 0.4 m3/h, 1,000 bar, optional with subsequent flow cooling)
  • Membrane filtration (MF/UF) for desalination and product concentration processes; feeding up to 500 kg/h; flexible use of spiral wound modules (material, cut-off)
  • Fine purification using liquid chromatography (35-liter column volume, flow rate up to 180 L/h) 
  • Crystallizers (180 L, 800 L) with downstream vacuum fiter dryer (0.5 m2) in ATEX version 
  • Spray (5 kg/h) and freeze drying (0.8 m2) for finishing the products


Analytical equipment

  • Laboratories for microbiological tests
  • Qualitative and quantitative methods to determine the optical density and cell dry mass, the concentration of sugars, alcohols and organic acids, protein analysis
  • Various assays for measuring enzyme activity
  • Online measurement of the alcohol concentration in the reactor and CO2 / O2 in the fermentation exhaust gas

Infomaterialien

 

Broschüre »Industrielle Biotechnologie - Die Natur als chemische Fabrik«

Wissenschaftliche Publikationen

Group photo »Bioprocess scale-up«
© Fraunhofer CBP
Group photo »Bioprocess scale-up«