A versatile multi-dimensional ratiometric sensor exploiting material-interface properties for t-Tau protein detection in human serum

Ratiometric sensor provides self-calibration for enhanced reliability, but conventional single-ratio designs are validated only under fixed instrumental conditions, making their reliability environment-dependent and inherently non-transferable to other analytical scenarios. Herein, we exploited the physical, chemical and interfacial changes inherent to sensor fabrication to extract multiple orthogonal signals from a single interface, constructing a versatile multi-dimensional ratiometric sensor that simultaneously enhanced accuracy and scenario adaptability. As proof of concept, this sensor was applied to detect total tau protein (t-Tau), a key Alzheimer's disease (AD) biomarker. Electrospun Fe-MOF/polyacrylonitrile nanofibers on a glassy carbon electrode served as the substrate, providing a stable redox peak current (I_p) and a photothermal temperature signal (T) as intrinsic references. Target recognition triggered a catalytic hairpin assembly that released a Ru-MOF-labeled probe, generating dynamic electrochemiluminescence (I_ECL) and charge-transfer resistance (R_ct) responses. After blank correction, the dynamic signals were integrated with the two references to yield five independent ratiometric outputs (ΔR_ct/I_p, ΔR_ct/ΔT, ΔR_ct/ΔI_ECL, ΔI_ECL/ΔT, ΔI_ECL/I_p), all exhibiting detection limits (3.4-4.1 fg mL^-1) three orders of magnitude below the AD diagnostic threshold (21.3 pg mL^-1). This demonstrated each ratio as an independently valid strategy for flexible deployment across varied scenarios. Receiver operating characteristic (ROC) analysis confirmed robust discriminatory power across all five ratios (area under the ROC curve 0.80-0.95), enabling both mutual cross-validation among outputs and flexible selection of the optimal ratio for available instrumentation. Collectively, by exploiting material-interface properties, this work provided a versatile platform for accurate biomarker detection adaptable to diverse analytical scenarios and laboratory settings.