A Point-of-Care Test to Measure Tacrolimus Directly from Unprocessed Whole Blood

Tacrolimus is a cornerstone immunosuppressant used to prevent graft rejection in solid organ transplant recipients. While effective, tacrolimus therapy must be carefully monitored and managed due to the drug's narrow therapeutic window and variable patient responses to dosing. Overdosing of tacrolimus can lead to opportunistic infections, nephrotoxicity, neurotoxicity, and cancer while under-dosing risks organ rejection. As a result, therapeutic drug monitoring (TDM) of tacrolimus is routinely performed. Current monitoring approaches face significant limitations, including slow (4-8 h or days) turnaround times, complex sample preparation requirements, and reliance on centralized infrastructure that delays critical dosing decisions. Furthermore, emerging evidence shows that the pharmacokinetic exposure parameter best associated with clinical outcomes is the area under the concentration-time curve (AUC). AUC-based monitoring requires sampling patients at multiple time points, which increases the logistical burdens to both patients and providers. Hence, there is an urgent need for a point-of-care test for tacrolimus that can be run at the patient bedside, in outpatient clinics, and eventually in patient homes. Here, we describe a novel point-of-care test, the TAC-D4 POCT, capable of measuring tacrolimus levels directly from whole blood samples without sample preparation steps or expensive analyzers with automated results available in 1 h. Our test helps overcome the current logistical barriers in the clinical management of patients receiving tacrolimus therapy ultimately leading to improved patient adherence, outcomes, and the ability to further personalize dosing regimens. Moreover, the Tac-D4 is highly modular and can be used to monitor clinically significantly biomarkers, such as interleukin-6 and matrix metalloproteinase 3, that complement tacrolimus TDM.