期刊
TUBERCULOSIS
卷 92, 期 5, 页码 407-416出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.tube.2012.05.009
关键词
Tuberculosis; Diagnosis; Lipoarabinomannan; Early secretory antigenic target 6; Antigen 85 complex; Waveguide-based optical biosensor
资金
- Intramural Research Program of the NIAID, NIH
- South Korean Ministry of Health, Welfare and Family Affairs
- WHO/FIND [A50452]
- Special Programme for Research and Training in Tropical Diseases
- Department of Energy
- Los Alamos National Laboratory LDRD Directed Research Award
Early diagnosis of active tuberculosis (TB) remains an elusive challenge, especially in individuals with disseminated TB and HIV co-infection. Recent studies have shown a promise for the direct detection of pathogen-specific biomarkers such as lipoarabinomannan (LAM) for the diagnosis of TB in HIV-positive individuals. Currently, traditional immunoassay platforms that suffer from poor sensitivity and high nonspecific interactions are used for the detection of such biomarkers. In this manuscript, we demonstrate the development of sandwich immunoassays for the direct detection of three TB-specific biomarkers, namely LAM, early secretory antigenic target 6 (ESAT6) and antigen 85 complex (Ag85), using a waveguide-based optical biosensor platform. Combining detection within the evanescent field of a planar optical waveguide with functional surfaces that reduce non-specific interactions allows for the ultra-sensitive and quantitative detection of biomarkers (an order of magnitude enhanced sensitivity, as compared to plate-based ELISA) in complex patient samples (urine, serum) within a short time. We also demonstrate the detection of LAM in urine from a small sample of subjects being treated for TB using this approach with excellent sensitivity and 100% corroboration with disease status. These results suggest that pathogen-specific biomarkers can be applied for the rapid and effective diagnosis of disease. It is likely that detection of a combination of biomarkers offers greater reliability of diagnosis, rather than detection of any single pathogen biomarker. NCT00341601. (C) 2012 Elsevier Ltd. All rights reserved.
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