Molecularly imprinted polymers: A closer look at the template removal and analyte binding

Molecularly imprinted polymers (MIPs), which first appeared over half a century ago, are now attracting considerable attention as artificial receptors, particularly for sensing. MIPs, especially applied to biomedical analysis in biofluids, contribute significantly to patient diagnosis at the point of care, thereby allowing health monitoring. Despite the importance given to MIPs, removal of templates and binding of analytes have received little attention and are currently the least focused steps in MIP development. This critical review is dedicated to a comprehensive analysis and discussion of cutting-edge concepts and methodologies in the removal and binding steps pertaining to various types of analytes, including ions, molecules, epitopes, proteins, viruses, and bacteria. The central objective of this review is to comprehensively examine and discuss a range of removal methods, including soxhlet extraction, immersion, microwave-assisted technique, ultrasonication, electrochemical approach, and proteolytic digestion, among others. Additionally, we will explore various binding methods, such as soaking, drop-casting, and batch sorption, to provide a comprehensive overview of the subject. Furthermore, the current challenges and perspectives in removal and binding are highlighted. Our review, at the interface of chemistry and sensors, will offer a wide range of opportunities for researchers whose interests include MIPs, (bio)sensors, analytical chemistry, and diagnostics.