Table 5.

Comparison of the most advantageous continuous fermentation methods and configurations for solvent production with solventogenic and acetogenic clostridia

Method/configuration	Advantages	Disadvantages	References
One-stage chemostat	Maintain growth rate at defined value Supports growth-related products Stable gas fermentation with acetogens	Maximum growth rate limited by dilution rate Low biomass during solvent formation Strain degeneration and difficulty to reach steady state conditions with solventogenic clostridia	[18, 193, 319]
Multi-stage systems	Tool to stabilize biphasic fermentations Variation of temperature, pH or nutrient supply between the stages	Higher costs for multiple reactors Complex control	[18, 205, 247, 275, 279]
Cell retention	Uncouples dilution rate of specific growth rate High volumetric productivity Full control of biocatalyst concentration Increased conversion rates (Toxic) solvents can easily be recovered of cell-free permeate Circulation of effluent possible Biomass reuse lowers propagation costs	Difficult long-term operation Costly membrane Membrane fouling At high-level biomass concentration operational problems (high viscosity, heavy gas formation and foaming) Higher contamination risk of external separation Nonselective retention (dead, non-viable cells, and substrate particles) Requirement of cell viability monitoring	[21, 62, 161, 164, 185, 204, 222, 287, 308, 314]
Cell immobilization and biofilm reactors	Prevents washout of cells Allows higher dilution rates Increases reaction rates and productivity Enhanced genetic stability Improved inhibitor resistance of cells Protects cells against shear forces	Uncontrolled cell growth can lead to blocking or Membrane fouling Maintenance of cell viability and physiology Diffusion limitation of mass-transfer Varying microenvironment Leaking of cells of support Inactive or dead biomass Reduced productivity during longer-term operation Challenging scale-up	[11, 138, 150, 168, 179, 205, 225, 231, 275, 284, 314, 341]
Integrated product recovery	Energy-efficient at low solvent concentrations Integration of downstream step for solvent recovery into cultivation Operable in continuous mode Lowers the concentration of toxic products in the broth Decreased product inhibition Improved substrate conversion rates, solvent yields, and productivities In situ product recovery: culture broth does not leave the reactor	In-line method in separate recovery loop affecting the cells In situ product recovery: limited optimization opportunities Disadvantages dependent on product recovery method	[21, 58, 82, 161, 164, 306, 325]