Organic polymer-based monoliths: structural design and integration into microreactors and flow analytical systems

Approximately three decades ago, in response to the growing demand for rapid and sensitive analysis of small-volume samples, monolithic column technology emerged contemporaneously with other key concepts in analytical chemistry, such as the micro-total analysis system (µTAS) and lab-on-a-chip technology. These innovations attracted considerable attention as paradigm-shifting tools in the field. In the post-genomic era in particular, where miniaturization and high-throughput workflows became critical, monoliths-characterized by their continuous porous structure, high permeability, and low back pressure-were recognized as next-generation separation media, especially in omics-driven research. However, subsequent advances in liquid chromatography-most notably the development of core-shell particle packing materials and the widespread adoption of ultra-high-performance liquid chromatography (UHPLC)-gradually diminished the relative advantages of monolithic columns in standard high-throughput HPLC applications. Despite this shift, their intrinsic features, including ease of fabrication, outstanding flow properties, and flexible moldability into diverse formats, have continued to generate new value. In recent years, applications of monoliths have expanded beyond analytical separations into diverse fields, including biopharmaceutical purification (e.g., antibody drugs), solid-phase extraction, immobilized catalytic systems, and integration into micro- and nanoscale devices. This review provides a comprehensive overview of the three-decade evolution of monolithic column technology, highlighting its historical context, current applications, and emerging roles in both analytical and preparative sciences within the broader context of evolving analytical technologies.