Table 5.

The current high-density-culture methods showing advantages and disadvantages.

Current High-Density-Culture Methods	Advantage	Disadvantages
Buffer salt culture [179]	Add a buffer salt that has no effect on the strain or has a growth-promoting impact on the culture medium to improve the buffering capacity of the fermentation broth and control the stability of pH within a specific range, easy to operate.	The buffering capacity of the buffer salt is limited and can only play a role within a specific range.
Chemical neutralization culture [180]	Add lye (such as NaOH, ammonia, and CaCO3) to the culture system to control the pH value of the fermentation system, easy to operate.	With the continuous addition of lye and the accumulation of metabolites, too high salt concentration will inhibit the growth of bacteria.
Dialysis culture [181]	Remove part of the small molecular metabolites produced by the bacteria while providing fresh nutrients to the culture solution.	A small processing volume, a long dialysis process, and large equipment investment are also not conducive to industrialization.
Fed-batch culture (non-feedback mode and feedback mode) [182,183,184,185]	Effectively eliminates substrate inhibition and acid inhibition and is simple to operate	Inadequate utilization of nutrients; Limited by container volume
Cross-flow culture [186]	Due to cross-flow filtration, the high viscosity produced by cells is reduced, which is conducive to cell recovery and high concentration	High equipment cost; Requires more professional operators; It is easy to block the membrane module.
Circulating culture (sedimentation, centrifugation, and membrane filtration) [187,188]	Through technologies such as sedimentation, centrifugation, and membrane filtration, the cells are intercepted, the culture medium flows out, and then a certain amount of fresh culture medium is added to obtain high-density cells. It shortens the production time and saves a lot of power, workforce, water, and steam	In the circulation process, the strains quickly degenerate and are polluted, resulting in economic losses; The utilization rate of nutrients was lower than that of batch culture.