Interface control in detectors: Enhancing the sensitivity of paper-based microfluidic chips for biomarker detection

Paper-based microfluidic analytical devices (μPADs) have found extensive application in rapid and sensitive biomarker detection, owing to their cost-effectiveness, minimal sample consumption, and portability. The analytical sensitivity of μPADs fundamentally depends on the interfacial performance of integrated detection modules within microfluidic systems, which arises from surface physicochemical phenomena at the critical interface between analytes and the sensing substrate. Consequently, the strategic design and structural optimization of recognition interfaces emerge as pivotal considerations in advancing high-sensitivity detection systems for biomarkers. However, the instability of paper-based interface modifications and the complexity associated with high-precision design and manufacturing of microchannel structures have hindered significant improvement in the interface sensitivity of paper-based microfluidic chip detectors. To systematically construct high-performance paper-based microfluidic chips from the perspective of interfacial structural design and elucidate the associated performance enhancement mechanisms, this review evaluates cutting-edge developments in enhancing μPADs sensitivity through interface engineering strategies. It provides a systematic appraisal of their deployment in biomarkers detection. We systematically analyze methods for constructing multi-scale-functionalized detection interfaces using multidimensional materials and discuss the detection mechanisms of interface-engineered detectors. The analysis further delineates emergent challenges and unexplored opportunities in interfacial engineering for μPADs. These rationally designed interfacial architectures demonstrate significant potential for transforming operational frameworks in field-deployable, ultrasensitive biomarker detection.