A light-operated dual-mode method for neuroblastoma diagnosis based on a Tb-MOF: from biometabolite detection to logic devices

Exploring simple analytical techniques with high accuracy and reliability to quantify biomolecules is crucial, but it remains a great challenge for disease diagnosis. Since the body fluid concentration of most biological targets usually varies in a rather limited range between normal and pathological states, and most systems are greatly limited by a single mechanism/mode of detection, which makes them susceptible to false positive/negative results. Herein, we successfully synthesized a double-mechanism-driven fluorescent sensor based on a Tb-based metal-organic framework (Tb-DBA), which performs quantitative recognition of urinary vanillylmandelic acid (VMA) as an early pathological signature of neuroblastoma (NEURO) accompanied by two completely different luminescence phenomena in a smaller concentration window by switching the excitation wavelength. Notably, Tb-DBA shows high sensitivity, great selectivity, and low detection limit toward epinephrine (EP, the metabolic precursor of VMA). The bifunctional detector based on Tb-DBA inherently improves analytical reliability and greatly reduces the chance of false negatives/positives for NEURO diagnosis. In addition, a one-to-two logic gate based on the interaction between Tb-DBA and VMA was constructed for the analysis of VMA level, which can be further used for NEURO diagnosis. This work represents the first example to design a luminescent sensor coupled with multiple mechanisms in a single sensing platform for the diagnosis of NEURO, providing a new avenue for the clinical application of two-dimensional detection biomarkers for accurate diagnosis in serious diseases.