(Cu-S)

Early and accessible diagnosis of tuberculosis (TB) remains a global health challenge, particularly in low- and middle-income countries. Early Secreted Antigenic Target 6 kDa (ESAT-6), released during initial infection, is a promising biomarker for TB detection. However, most current assays for TB detection depend on complex instrumentation and trained personnel, limiting their utility in resource-constrained settings. Here, we developed dual biosensing platforms based on a (Cu–S)n metal-organic framework–polyaniline (MOF–PANI) composite for ESAT-6 detection in blood plasma and urine. A paper-based microfluidic resistive immunosensor with pulsed light sintering optimization enabled quantification through resistance changes, achieving a detection range of 195 pM–50 nM with a limit of detection (LOD) of 39.2 pM in human blood plasma. In parallel, a glassy carbon electrode–based electrochemical sensor was fabricated by covalent antibody immobilization on MOF–PANI, followed by bovine serum albumin (BSA) blocking. Cyclic voltammetry revealed a detection range of 23.6 fM–1.56 nM with an ultralow LOD of 1.68 fM in artificial urine, along with excellent reproducibility and stability. Together, these results highlight the versatility of MOF–PANI composites in enabling multi-matrix ESAT-6 detection, offering complementary advantages of blood plasma-based point-of-care testing and urine-based non-invasive diagnostics. This integrated strategy shows strong potential for scalable, accessible, and accurate early TB diagnosis.