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Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor

Title
Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor
Authors
Harshini Mukundan;Sandeep Kumar;Basil I. Swanson;Ramamurthy Sakamuri;Clifton Barry III;Laura E. Via;Sang Nae Cho;Soo Hee Hwang;Aaron S. Anderson;W. Kevin Grace;Jesse M. Resnick;Jessica Kubicek-Sutherland;Seokyong Eum;Seonyeong Min;Ye-Jin Lee;Sonja M. Ray;Dominique N. Price
Issue Date
2012
Journal Title
Tuberculosis
ISSN
1472-9792
Citation
Tuberculosis, Vol.92(5) : 407~416, 2012
Abstract
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.
URI
http://www.sciencedirect.com/science/article/pii/S1472979212001278

http://ir.ymlib.yonsei.ac.kr/handle/22282913/91981
DOI
10.1016/j.tube.2012.05.009
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Microbiology
Yonsei Authors
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