Structure Engineering of a Lanthanide‐Based Metal–Organic Framework for the Regulation of Dynamic Ranges and Sensitivities for Pheochromocytoma Diagnosis

Exploring innovative technologies to precisely quantify biomolecules is crucial but remains a great challenge for disease diagnosis. Unfortunately, the humoral concentrations of most biotargets generally vary within rather limited scopes between normal and pathological states, while most literature‐reported biosensors can detect large spans of targets concentrations, but are less sensitive to small concentration changes, which consequently make them mostly unsatisfactory or even unreliable in distinguishing positives from negatives. Herein, a novel strategy of precisely quantifying the small concentration changes of a certain biotarget by editing the dynamic ranges and sensitivities of a lanthanide‐based metal–organic framework (Eu‐ZnMOF) biosensor is reported. By elaborately tailoring the biosensor's structure and surface areas, the tunable Eu‐ZnMOF is developed with remarkably enhanced response slope within the “optimized useful detection window,” enabling it to serve as a powerful signal amplifier (87.2‐fold increase) for discriminating the small concentration variation of urinary vanillylmandelic acid (an early pathological signature of pheochromocytoma) within only three times between healthy and diseased subjects. This study provides a facile approach to edit the biosensors' performances through structure engineering, and exhibits promising perspectives for future clinical application in the non‐invasive and accurate diagnosis of severe diseases. A tunable lanthanide‐based metal–organic framework biosensor for precisely quantifying small concentration changes of urinary vanillylmandelic acid (VMA), the early pathological signature of pheochromocytoma, is designed by editing its dynamic ranges and sensitivities. By tailoring the biosensor's structure, its dynamic range is narrowed to the “useful VMA window” with remarkably enhanced response slope, enabling it as a powerful signal‐amplifier for discriminating positives from negatives.