Abstract

Optical sensing and imaging have perceived massive success in biomedical analysis and disease diagnosis in terms of minimal invasiveness, good sensitivity, high accuracy, and time‐/cost‐effectiveness. Upconversion nanoparticles (UCNPs) as a kind of promising luminescent material hold many merits like unique frequency‐converting capability, emission fine‐tuning, low auto‐fluorescence interference, good tissue‐penetration ability, high photostability, and excellent biocompatibility, which are widely applied for optical sensing of diverse chemically or biologically derived analytes. Extensive efforts are dedicated to the rational fabrication of reliable upconversion nanoplatforms (UCNs) through ingenious modulation of the luminescent energy transfer process for various optical biosensing applications. Herein, the advancement of biomacromolecules (e.g., nucleic acids, proteins, and enzymes) detection using multiplex UCNs from on‐paper platforms to in‐solution as well in living systems is specifically focussed. Detailed summarizations of the probe design strategy, responsive mechanisms, and sensing performance have been presented. In addition, based on the current research achievements, the challenges and future perspectives are emphasized to facilitate further clinical sensing utilizations with upconversion photonic technology.

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