Preparation and application of porous framework materials for bio-separation

Abstract

Efficient and precise bioseparation is essential and increasingly urgent for advancing life sciences and biotechnology. This demand is amplified by precision medicine, which requires isolating, enriching, characterizing and utilizing low-abundance, complex biomolecules, including post-translationally modified peptides, proteins and metabolites. Conventional separation techniques are unable to handle this challenge, which results in significant bottlenecks in the development of targeted drugs, biomarker discovery, and individualized therapeutic monitoring. Porous framework materials offer transformative solutions via structural tunability, ultrahigh surface areas and tailor-made pore chemistries: metal–organic frameworks (MOFs) enable selective protein separation and modified peptide enrichment through hydrophilic/metal coordination interactions, covalent organic frameworks (COFs) minimize protein denaturation with high stability and modifiable surfaces, and hydrogen-bonded organic frameworks (HOFs) achieve gentle, efficient aqueous biomarker enrichment via intrinsic biocompatibility and dynamic hydrogen bonding. This review systematically classifies MOFs, COFs, and HOFs and summarizes their applications in the separation and analysis of small-molecule drugs, phosphopeptides, glycopeptides, and proteins. We also discuss the key challenges, including pre- and post-modification methodologies, the construction of chiral porous materials, and integration with magnetic microspheres. Finally, we highlight their future prospects in advancing bioseparation for precision medicine, diagnostics, and therapeutic development, driving progress across biotechnology and biomedical engineering.