Bilateral SERS-Microneedle Patch for Co-Diagnosis of Diabetes Mellitus and Tuberculosis Comorbidity

The prevalence of diabetes mellitus (DM) and tuberculosis (TB) comorbidity is constantly rising worldwide, thus there is an urgent need for a co-diagnostic method of TB-DM in the clinic. Here, we introduced a bilateral surface-enhanced Raman scattering (SERS)-microneedle (MN) patch that incorporated Au hybrid mesoporous polydopamine-coated urchin Au/Ag (U@mP@Au) for analyzing glucose in interstitial fluid (ISF) and TB biomarker (ESAT-6/CFP-10) in sputum toward the co-detection of TB-DM comorbidity. The feasibility of the bilateral SERS-MN patch was demonstrated in ex vivo artificial skin, in vivo mouse models, and trials of recruiting patients. In the clinical assessment, DM patients (N = 18) and healthy subjects (N = 3) were classified with satisfactory sensitivity (88.9%) and specificity (100%), among which one DM positive sample (P11) with TB infection was successfully identified. Results revealed the sensitivity (87.5%) and specificity (90.9%) of SERS-MN array for TB diagnosis (N = 33), which were comparable to traditional clinical methods (smear, TST, and Xpert). More importantly, three TB-positive patients (P9, P15, and P20) showed abnormally elevated glucose levels, which is highly suggestive of TB-DM complication. This integrated dual-analyte detecting platform represented a significant step toward the cooperative diagnosis of TB-DM comorbidity, facilitating the early detection of complications by clinicians.