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

Harshini Mukundan, Sandeep Kumar, Dominique N. Price, Sonja M. Ray, Ye Jin Lee, Seonyeong Min, Seokyong Eum, Jessica Kubicek-Sutherland, Jesse M. Resnick, W. Kevin Grace, Aaron S. Anderson, Soo Hee Hwang, Sang Nae Cho, Laura E. Via, Clifton Barry, Ramamurthy Sakamuri, Basil I. Swanson

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44 Citations (Scopus)

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. NCT00341601.

Original languageEnglish
Pages (from-to)407-416
Number of pages10
JournalTuberculosis
Volume92
Issue number5
DOIs
Publication statusPublished - 2012 Sep 1

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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    Mukundan, H., Kumar, S., Price, D. N., Ray, S. M., Lee, Y. J., Min, S., Eum, S., Kubicek-Sutherland, J., Resnick, J. M., Grace, W. K., Anderson, A. S., Hwang, S. H., Cho, S. N., Via, L. E., Barry, C., Sakamuri, R., & Swanson, B. I. (2012). Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. Tuberculosis, 92(5), 407-416. https://doi.org/10.1016/j.tube.2012.05.009