Rapid Detection of Mycobacterium tuberculosis Biomarkers using a Waveguide-based Biosensor
Autor: | Mukundan, Harshini, Kumar, Sandeep, Price, Dominique N., Ray, Sonja M., Lee, Ye-Jin, Min, Seonyeong, Eum, Seokyong, Sutherland, Jessica Kubicek, Resnick, Jesse M., Grace, W. Kevin, Anderson, Aaron S., Hwang, Soo Hee, Cho, Sang Nae, Via, Laura E., Barry, Clifton E., Sakamuri, Ramamurthy, Swanson, Basil I. |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Immunoassay
Lipopolysaccharides Male Antigens Bacterial Coinfection Reproducibility of Results Enzyme-Linked Immunosorbent Assay Biosensing Techniques Mycobacterium tuberculosis Sensitivity and Specificity Article Bacterial Proteins HIV Seropositivity Humans Female Reagent Kits Diagnostic Tuberculosis Pulmonary Acyltransferases Biomarkers |
Popis: | 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. |
Databáze: | OpenAIRE |
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