Fed-Batch Production of Bacterial Ghosts Using Dielectric Spectroscopy for Dynamic Process Control

Area of Science:

• Biotechnology
• Microbiology
• Process Engineering

Background:

• Bacterial Ghosts (BGs) are cell envelopes derived from Gram-negative bacteria using the lysis gene E from bacteriophage ϕX174.
• BGs show promise as vaccine candidates, immunotherapeutic agents, and drug delivery vehicles.
• The production of BGs is a complex process requiring precise control, especially during the lysis phase.

Purpose of the Study:

• To develop an economic and robust fed-batch production process for Bacterial Ghosts.
• To implement a control strategy for managing the rapid decline of viable biomass during the lysis phase.
• To enhance the yield and efficiency of BG production for commercial applications.

Main Methods:

• Utilized a transfer function combining dielectric spectroscopy and soft-sensor based biomass estimation.
• Developed a feed-controller integrated with the transfer function to monitor and manage biomass during lysis.
• Implemented the control strategy in a fed-batch production process for BGs.

Main Results:

• Achieved lysis efficiencies greater than 98%.
• Increased the yield of BG production by a factor of 8-10 compared to traditional batch methods.
• Demonstrated the ability to maintain a constant specific substrate uptake rate during the lysis phase.

Conclusions:

• The developed toolset provides effective process understanding and control for BG production.
• The enhanced production yield significantly improves the commercial potential of the Bacterial Ghost platform technology.
• This advancement facilitates the broader application of BGs in various fields, including medicine and biotechnology.