Bacterial Fermentation Service

BIC possesses a mature bacterial fermentation platform consisting of large fermentation tanks, bioreactors, and large-scale purification systems which enables us to provide high-purity and gram level proteins. BIC's bacterial fermentation services are available at any scale from 5 to 500L for both fed-batch and continuous cultivation. There are three types of fermentation services: standard fermentation service, high cell density fermentation (HCDF) service, and fermentation process optimization service. Our services include codon optimization, gene synthesis, small scale expression test, fermentation process optimization and protein purification. You only need to provide the gene sequence of your target protein or the established vector, and we will start the service as you select.

Flow Chart of Microbial Fermentation Process

Codon
optimization

Pilot expression
optimization

Batch
fermentation

Fed-batch
fermentation

Purification
optimization

Service Packages

We offer a one-stop fermentation service, from gene synthesis or subcloning to 5-500 L scaled fermentation. For all the services, we will charge a small scale expression test fee.

Standard fermentation service

Fermentation Scale		Turnaround time	Price	Deliverables
5-500L	Wet cell weight: 7~17g/L (OD600: 6-15)	2-4 weeks	Inquiry	Cell pellet Fermentation data QC datasheet

Note: Protein purification service is available (An extra charge is required) and we can deliver purified protein. The expected protein expression amount is 5-50mg/L.

High cell density fermentation service

Fermentation Scale		Turnaround time	Price	Deliverables
5-500L	Wet cell weight: 23-130g/L (OD600: 20-120)	3-5 weeks	Inquiry	Cell pellet Fermentation data QC datasheet

Note: Protein purification service is available (An extra charge is required) and we can deliver purified protein. The expected protein expression amount is 20-400mg/L.

Fermentation process optimization service

Fermentation Scale		Turnaround time	Price	Deliverables
5-500L	Wet cell weight: 23-130g/L (OD600: 20-120)	9-13 weeks	Inquiry	Recombinant protein (100-1000mg/L) Detailed protocol Fermentation data QC datasheet

Bacterial Fermentation Technology Platform

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 <em>E. coli</em> 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 biology laboratory provides services in microbial fermentation. It features a 1,000 sq. ft. pilot scale fermentation laboratory which is 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 production ensures stringently controlled of the pH, temperatures, aeration, dissolved oxygen content and agitation rate. 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. Adding 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 sampled by regular containers, and metabolic test ensures the final product meets your specification. The product can be sent as a freezing cell particle or further processing to produce concentrated protein extracts.

Cell Separation by Beckman centrifuge or continuous centrifuge

After growing in the fermentor, the cells are rapidly harvested by centrifugation.
For the size of fermentor between 10 Land 25 L, cells are achieved using a rotor centrifuge. The centrifuge has the capacity to spin 6 L fermented liquid at a time and both rotors can maintain a cold environment which can minimize protein degradation during centrifugation.
For cultures of 25 L and above, we use a continuous centrifuge to harvest the cells. Collecting the cells around the edge of the centrifuge bowl and harvesting them 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 used in downstream process to provide cells or protein extracts specific to meet customers’ requirements.

Need more information? Please do not hesitate to get in touch.

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+1 (855) 427-1516