Single-atom-pair encoded photoelectrochemical sensing of tacrolimus in whole blood for monitoring-informed immunosuppression in organ transplantation

Therapeutic drug monitoring of tacrolimus (TAC) is essential for maintaining immune tolerance after organ transplantation, yet conventional assays often provide delayed and discontinuous measurements that constrain timely dose adjustment during periods of rapid pharmacokinetic fluctuation. Here we report a photoelectrochemical (PEC) TAC sensor that encodes molecular recognition at Ni₁Cu₂ single-atom pairs anchored on TiO₂ photoelectrodes. Cooperative metal sites selectively engage TAC nitrogen and oxygen donors, enabling receptor-free recognition and controlled interfacial oxidation. An antifouling hydrogel interface suppresses nonspecific adsorption and preserves signal fidelity in protein- and cell-rich matrices, enabling minute-scale quantification at clinically relevant concentrations. The assay achieves an LOD of 0.1 ng mL⁻¹ with a linear range of 0.5-20 ng mL⁻¹ and maintains stability under biofouling challenge. In 120 transplant patient samples, PEC readouts agree with routine chemiluminescent immunoassay results across the therapeutic range. Finally, in rat liver and mouse heart transplantation models, monitoring-informed dosing adjustment improved survival compared with conventional dosing. By shortening the measurement-to-decision interval, this work provides a robust PEC sensing framework for TAC TDM in whole blood and supports more timely immunosuppressive management.