A Critical Review on Covalent Organic Frameworks as Emerging Electrocatalysts for Electrochemical Glucose Sensing

In this review we systematically examine covalent organic framework (COF)-modified electrodes for enzymatic and nonenzymatic electrochemical glucose biosensors, with an emphasis on structure-property-performance relationships. The five failure modes of conventional sensing materials biological fragility, low conductivity, alkaline pH dependence, aqueous instability, and poor selectivity in complex matrices are identified as the central design problem, and the four structural advantages of COFs that simultaneously address these failure modes are analyzed mechanistically. The design, synthesis, functionalization and electrode integration procedures of COFs are critically compared, with particular attention to how linkage chemistry, pore geometry, π-conjugation length, and heteroatom identity quantitatively determine sensing performance parameters including limit of detection, sensitivity, linear range, and operational stability. Both enzymatic (Generation 1-4) and nonenzymatic sensing mechanisms are discussed comparatively. Current challenges are critically evaluated alongside emerging opportunities in wearable devices, molecularly imprinted COF platforms, and smartphone-enabled colorimetric sensing. Specific research directions required to bridge the gap between laboratory proof-of-concept and clinically viable glucose monitoring devices are outlined.