Electrochemical sensing of macromolecules based on molecularly imprinted polymers: challenges, successful strategies, and opportunities

Looking at the literature focused on molecularly imprinted polymers (MIPs) for protein, it soon becomes apparent that a remarkable increase in scientific interest and exploration of new applications has been recorded in the last several years, from 42 documents in 2011 to 128 just 10 years later, in 2021 (Scopus, December 2021). Such a rapid threefold increase in the number of works in this field is evidence that the imprinting of macromolecules no longer represents a distant dream of optimistic imprinters, as it was perceived until only a few years ago, but is rapidly becoming an ever more promising and reliable technology, due to the significant achievements in the field. The present critical review aims to summarize some of them, evidencing the aspects that have contributed to the success of the most widely used strategies in the field. At the same time, limitations and drawbacks of less frequently used approaches are critically discussed. Particular focus is given to the use of a MIP for protein in the assembly of electrochemical sensors. Sensor design indeed represents one of the most active application fields of imprinting technology, with electrochemical MIP sensors providing the broadest spectrum of protein analytes among the different sensor configurations.