Tetrad metal ion mediated molecular switch aptamer sensor for fluorescence assay of plasma IP-10 in clinical tuberculosis

Interferon-γ-inducible protein 10 (IP-10) has demonstrated enormous potential as a novel biomarker for tuberculosis (TB), particularly in the monitoring of patient progression for active or latent tuberculosis infection (LTBI). Herein, we established a tetrad metal ion-mediated molecular switch aptamer sensor for the convenient detection of IP-10 in plasma and the diagnosis of TB. The simple sensor relied on the partially complementary IP-10 aptamer and four DNA hairpin strands rich in cytosine (C), which can form a relatively stable tetrad C-Ag+-C structure when combined with Ag+ without additional modification. Based on the specific recognition of IP-10 and aptamer, a large amount of Ag+ could be released in a short time. Combining with cadmium telluride quantum dots (CdTe QDs) as the signal reporter, we achieved superior analytical performance, with the limits of detection (LOD) reaching 3 fg/mL for IP-10 analysis in 1 h. Clinical practicality was confirmed by evaluating 38 clinical samples (19 TB-positive patients, 14 non-TB patients, and 5 latent TB infection patients). The results showed that the detected IP-10 levels were significantly different between the non-TB and TB/LTBI groups, and the results aligned with clinical computed tomography (CT) results, indicating that the method could represent a reliable diagnostic technique for TB. •A homogeneous, simple, and highly sensitive IP-10 detection system for TB diagnosis was established.•The tetrad metal ion mediated molecular switching aptamer sensor enhanced the efficiency of selective recognition.•The system was successfully applied to the analysis of 38 plasma samples and showed good consistency with clinical evidences.