Next‐Generation Chromatography: Covalent Organic Frameworks in Biomedical Analysis

ABSTRACT Chromatography, a cornerstone technique in analytical chemistry, continues to evolve with the emergence of novel stationary phases. Covalent organic frameworks (COFs) have garnered significant attention due to their unique properties and versatile applications. COFs, composed of covalently linked organic building blocks, exhibit high surface area, tunable porosity, and exceptional chemical stability. These attributes make them next‐generation chromatographic techniques that leverage novel materials and methodologies to achieve significant improvements in separation efficiency, selectivity, speed, and/or sensitivity compared to traditional methods. COF stationary phases demonstrate remarkable selectivity for small molecules, peptides, proteins, and nucleic acids. Their use in drug discovery, metabolomics, proteomics, and clinical diagnostics is gaining momentum. In this review, we explored their synthesis strategies, emphasizing the design principles that enable tailoring of their physicochemical properties. Further, we discuss the immobilization of COFs onto solid supports, ensuring their compatibility with existing chromatographic systems. Furthermore, we highlighted case studies where COFs outperformed traditional stationary phases, improving sensitivity and resolution. We delve into the integration of COFs as stationary phases in biomedical analysis and explore various strategies for utilizing COFs as stationary phases in chromatographic separations.