Downstream Separation Technologies for Bio-isobutanol: Challenges, Strategies, and Emerging Solutions

Bio-isobutanol has emerged as an attractive next-generation biofuel and platform chemical due to its high energy density, low hygroscopicity, and compatibility with existing fuel infrastructures. Microbial production of isobutanol via engineered metabolic pathways has advanced significantly over the past decade; however, downstream separation remains one of the major bottlenecks limiting industrial implementation. The relatively low titers in fermentation broths (typically 5–30 g L⁻1), the presence of water-rich matrices, and the formation of azeotropes render conventional separation energy-intensive. Consequently, the development of efficient and cost-effective recovery technologies is critical for the commercialization of bio-isobutanol processes. This review provides a comprehensive overview of downstream separation strategies for bio-isobutanol recovery from fermentation broths. Key techniques including distillation, gas stripping, adsorption, liquid–liquid extraction, pervaporation, salting-out extraction, and hybrid integrated processes are discussed in terms of separation mechanisms, operational performance, and process integration potential. Particular emphasis is placed on emerging intensified approaches such as membrane-assisted extraction, in situ product removal, and hybrid separations combining thermodynamic and kinetic selectivity. Finally, the challenges and future perspectives toward energy-efficient and scalable bio-isobutanol separation technologies are discussed.