Optical thin films incorporating NaYF(4):Er,Yb upconverting nanorods and chromoionophore ETH 5418 in hydrophobic polymer matrixes have been developed for the first time to measure pH and metal ions based on the ion-exchange mechanism. The absorption spectra of protonated and unprotonated ETH 5418 overlap the two emission peaks of upconverting material, respectively, which makes the inert nanorods ion-sensitive. Optodes for pH and metal ions (Na(+), K(+), Ca(2+), and Cu(2+)) were investigated and exhibited excellent sensitivity, selectivity, and reproducibility. Because of excitation by the 980 nm laser source, detection in the near-infrared region at 656 nm, and high quantum yield of the nanorods in hydrophobic membrane, the proposed sensors have been successfully used in whole blood measurements with minimized background absorption and sample autofluorescence.
Improved tuberculosis (TB) prevention and control depend critically on the development of a simple, readily accessible rapid triage test to stratify TB risk. We hypothesized that a blood protein-based host response signature for active TB (ATB) could distinguish it from other TB-like disease (OTD) in adult patients with persistent cough, thereby providing a foundation for a point-of-care (POC) triage test for ATB. Three adult cohorts consisting of ATB suspects were recruited. A bead-based immunoassay and machine learning algorithms identified a panel of four host blood proteins, interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF), that distinguished ATB from OTD. An ultrasensitive POC-amenable single-molecule array (Simoa) panel was configured, and the ATB diagnostic algorithm underwent blind validation in an independent, multinational cohort in which ATB was distinguished from OTD with receiver operator characteristic–area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%). When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity. A blood-based host response panel consisting of four proteins and antibodies to one TB antigen can help to differentiate ATB from other causes of persistent cough in patients with and without HIV infection from Africa, Asia, and South America. Performance characteristics approach World Health Organization (WHO) target product profile accuracy requirements and may provide the foundation for an urgently needed blood-based POC TB triage test.
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