Harnessing cellulose-binding modules for advanced biosensing: principles, progress, and perspectives

초록

Cellulose, the most abundant natural polymer, has emerged as a sustainable platform for biosensing owing to its renewability, low cost, and biocompatibility. However, conventional probe immobilization methods on cellulose are limited by uncontrolled orientation, instability, and poor reproducibility. To overcome these barriers, cellulose-binding modules (CBMs), non-catalytic domains of carbohydrate-active enzymes, have been engineered as versatile molecular anchors. Recent studies have demonstrated that CBM fusions with enzymes, antibodies, nanobodies, nucleic acids, and reporter proteins enable oriented, high-density, and stable immobilization on cellulose scaffolds, thereby transforming cellulose from a passive carrier into an active, programmable substrate. CBM-based biosensors have been successfully applied in colorimetric, fluorescent, electrochemical, and phage-assisted platforms, achieving detection ranges from femtomolar protein biomarkers to single-colony bacterial pathogens, as well as clinically relevant monitoring of metabolites such as glucose, uric acid, and lactate. These advances underscore the potential of CBM fusion technology to improve sensitivity, reproducibility, and robustness compared to conventional cellulose-based assays. Despite these promising developments, challenges remain in clinical validation, environmental stability, and integration into portable diagnostic devices. Addressing these issues through protein engineering, nanostructured cellulose materials, and device-level innovation is expected to accelerate the translation of CBM-enabled biosensors into practical applications for healthcare, environmental monitoring, and food safety.Graphical Abstract CBM-based functional materials for enhanced sensitivity, reproducibility, and robustness of biosensing applications

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