Fermentation Service

BiologicsCorp (Abbr. BIC) offers bacterial fermentation services to produce industry-scale protein from batch, fed-batch and continuous cultures up to 500 liters of bacteria. Through a variety of optimization techniques including codon, pilot expression and fed-batch fermentation optimization as well as purification optimization, BIC can offer optimal solution for high level production of recombinant proteins with guaranteed purity.

Flow chart of microbial fermentation process

Fermentation Service Process
Codon
optimization
Pilot expression
optimization
Batch
fermentation
Fed-batch
fermentation
Purification
optimization

Selection guide of BIC’s bacterial fermentation services

Characteristics Standard fermentation High cell density fermentation Process optimization
OD600 6-15 20-120 20-120
Wet cell weight(g/L) 7-17 23-130 23-130
Purification optimization N/A N/A Available
Expected protein final yield(mg/L) 5-50 20-400 100-1000
Timeline 1 week 3 weeks 8-12 weeks
Price Start from $390 Start from $690 Please inquire
Deliverables
  • Cell pellet
  • Fermentation data
  • QC datasheet
  • Cell pellet
  • Fermentation data
  • QC datasheet
  • Recombinant protein with high purity
  • Detailed protocol
  • Fermentation data
  • QC datasheet

Detailed description about high cell density fermentation

The high cell density fermentation by fed-batch strategies is one of the most cost-effective means of achieving high yields for the production of heterologous proteins, which is widely used in the bio-industry. In fed-batch cultures, cell mass and productivity are maximized by controlling culture conditions such as the temperature and pH, the composition of the feed media, and the substrate feed rate.

High cell density fermentation study on E. coli strain

(A) Shake flask and low cell density processes.

  • shake flask, complex medium (2xYT);
  • shake flask, defined medium;
  • bioreactor batch process (low cell density);
  • bioreactor batch process (low cell density);

(B) High cell density processes.

  • bioreactor fed-batch process, induction at 25°C for 10 hours;
  • bioreactor fed-batch process, induction at 25°C for 10 hours;
  • bioreactor fed-batch process, induction at 15°C for 24 hours;
  • bioreactor fed-batch process, induction for 24 hours with stepwise temperature reduction.
High cell density fermentation study on E. coli strain.
Cell concentration was estimated by measuring optical density at 600 nm.
The BIC (BiologicsCorp) bioprocess facility provides services in microbial fermentation. It features a 1,000 sq. ft. pilot scale fermentation laboratory capable of handling class II organisms, an adjoining 500 sq. ft. bench scale cell culture, and fermentation laboratory with multiple fermentors and bioreactors for microbial. The facility can manufacture recombinant proteins and metabolites, as well as media optimization and cell culture scalability experiments. The fermentation facility provides you with seed culture development and culture scale-up from shake flasks to pilot scale fermentors.

Two benchtop fermentors configured with five-liter vessels are available for comparative studies. Batch, fed-batch and continuous cultures of 5 to 500 liters of yeast, bacteria are produced under stringently controlled conditions using four state-of-the-art fermentors.

At the pilot scale, two 100-liter fermentors and one 500-liter fermentor are available. Constant monitoring of each run ensures the pH, temperatures, aeration, dissolved oxygen content and agitation rate can be stringently controlled. As a result we are able to accurately reproduce growth conditions to provide consistency in the quality of product produced. Support equipments include shaker incubators, laminar flow hoods, chemical hoods, clean steam, microscopes, autoclaves, cryostorage, and freeze-dryers.

It is accessible to add nutrients or induction chemicals at any point during a run. Addition of nutrient and components during the run allows fed-batch and induction experiments to be performed. Optimization experiments can also be achieved, as regular sampling through a sterile sample port is possible during the fermentation.

Quality control is maintained by regular vessel sampling, and metabolite testing ensures the final product meets your specification. The product can be sent as a frozen cell pellet or further processed to produce concentrated protein extracts.

Cell Separation by Beckman centrifuge or continuous centrifuge

  • After growing the culture in the fermentor, the cells are rapidly harvested by centrifugation.
  • For cultures of between 10 and 25L, cell harvesting is achieved using a rotor centrifuge. The centrifuge has the capacity to spin 6L of culture at a time and both rotors can be temperature controlled to minimize protein degradation during centrifugation.
  • For cultures of 25L and above, we use a continuous centrifuge for harvesting the cells. The cells collect around the edge of the centrifuge bowl and are easily harvested at the end of the run. The continuous centrifuge is also cooled by chilled water to reduce product degradation during centrifugation. Using this system we can harvest a 500L fermentor in a fraction of the time it would take using the rotor centrifuge.
  • Once harvested, the cells can be further downstream processed to provide cell or protein extracts specific to customer requirements.

Contact Us

  +1 (317) 703-0614
  +1 (855) 427-1516