Leap‐Type Response of Redox/Photo‐Active Lanthanide‐Based Metal–Organic Frameworks for Early and Accurate Screening of Prostate Cancer

Abstract The development of high‐accuracy technologies to distinguish the quite tiny concentration change of tumor markers between negative and positive is of vital significance for early screening and diagnosis of cancers, but is still a great challenge for the conventional biosensors because of their “gradual” detection mode. Herein, a unique “leap‐type” responsive lanthanide MOF‐based biosensor (designated as Tb‐CeMOF‐X) with defect‐mediated redox‐/photo‐activities is developed for precisely identifying acid phosphatase (ACP), an early pathological marker of prostate cancer (PCa) in serum. The engineered Tb‐CeMOF‐X probe achieves a bursting switch‐on luminescence at the critical concentration of ACP (9 U ⋅ L −1 ), while keeping silent below this threshold, undergoing a qualitative signal change from “zero” to “one” between negative and positive indicators and thus significantly improving the identification precision. Significantly, such “leap‐type” response performance can be further edited and amplified by rational defect engineering in the crystal structure to improve the accessibility of active centers, consequently maximizing the detection sensitivity toward ACP in the complex biological media. This study proposes the first paradigm for the development of “leap‐type” biosensors with ultra‐sensitive differentiation capability between negative and positive, and provides a potentially valuable tool for early and accurate screening of PCa.