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, Sangnae Cho, Laura E. Via, Clifton Barry, Ramamurthy Sakamuri, Basil I. Swanson

Research output: Contribution to journalArticle

41 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

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Biosensing Techniques
Mycobacterium tuberculosis
Immunoassay
Biomarkers
Tuberculosis
Urine
Coinfection
HIV Infections
Early Diagnosis
Enzyme-Linked Immunosorbent Assay
HIV
Antigens
Serum
lipoarabinomannan

All Science Journal Classification (ASJC) codes

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

Cite this

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, Sangnae ; Via, Laura E. ; Barry, Clifton ; Sakamuri, Ramamurthy ; Swanson, Basil I. / Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. In: Tuberculosis. 2012 ; Vol. 92, No. 5. pp. 407-416.
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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.",
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Mukundan, H, Kumar, S, Price, DN, Ray, SM, Lee, YJ, Min, S, Eum, S, Kubicek-Sutherland, J, Resnick, JM, Grace, WK, Anderson, AS, Hwang, SH, Cho, S, Via, LE, Barry, C, Sakamuri, R & Swanson, BI 2012, 'Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor', Tuberculosis, vol. 92, no. 5, pp. 407-416. https://doi.org/10.1016/j.tube.2012.05.009

Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. / 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, Sangnae; Via, Laura E.; Barry, Clifton; Sakamuri, Ramamurthy; Swanson, Basil I.

In: Tuberculosis, Vol. 92, No. 5, 01.09.2012, p. 407-416.

Research output: Contribution to journalArticle

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AU - Mukundan, Harshini

AU - Kumar, Sandeep

AU - Price, Dominique N.

AU - Ray, Sonja M.

AU - Lee, Ye Jin

AU - Min, Seonyeong

AU - Eum, Seokyong

AU - Kubicek-Sutherland, Jessica

AU - Resnick, Jesse M.

AU - Grace, W. Kevin

AU - Anderson, Aaron S.

AU - Hwang, Soo Hee

AU - Cho, Sangnae

AU - Via, Laura E.

AU - Barry, Clifton

AU - Sakamuri, Ramamurthy

AU - Swanson, Basil I.

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N2 - 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.

AB - 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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