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Mukundan, Harshini; Kumar, Sandeep; Price, Dominique N; Ray, Sonja M; Lee, Ye-Jin; Min, Seonyeong; Eum, Seokyong; Kubicek-Sutherland, Jessica; Resnick, Jesse M; Grace, W. Kevin; Anderson, Aaron S; Hwang, Soo Hee; Cho, Sang Nae; Via, Laura E; Barry, Clifton; Sakamuri, Ramamurthy; Swanson, Basil I
Tuberculosis (Edinburgh, Scotland), 09/2012, Letnik: 92, Številka: 5Journal Article
Summary 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 non-specific 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.
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