Time‐Resolved Upconversion Lifetime Sensing for Selective Blood L‐Lactate Analysis During Postoperative Analgesia

Accurate and robust quantification of metabolic biomarkers in complex biological matrices is essential for understanding physiological responses during postoperative analgesia. Herein, we report a time‐resolved upconversion luminescence lifetime sensing platform for selective detection of L‐lactate in human blood. NaGdF ₄ /Yb/Er@NaGdF ₄ /Yb nanoparticle was integrated with L‐lactate‐specific aptamer to construct a lifetime responsive nanointerface for L‐lactate quantification. Benefiting from the intrinsic stability of lifetime‐based readouts, the proposed platform enabled reliable quantification independent of excitation fluctuations and probe concentration. The sensing system exhibited a linear detection range of 0–10 mM with a limit of detection of 0.39 mM, along with excellent selectivity against potential interferents and clear stereoselective discrimination between L‐ and D‐lactate. Moreover, the clinical applicability was validated in blood samples from healthy volunteers, showing strong agreement with standard clinical assays ( R ²  = 0.969). Furthermore, dynamic monitoring of postoperative patients revealed that circulating L‐lactate levels correlate with patient‐controlled analgesia demand, enabling effective pain stratification with an AUC of 0.894, achieving a sensitivity of 93.75% and a specificity of 84.38% at an optimal cutoff of 3.39 mM. This work provided a robust analytical strategy for integrating metabolic sensing with clinically relevant physiological assessment, offering new opportunities for objective pain evaluation in perioperative medicine.