Quantitative lateral-flow immunoassay for the assessment of the cartilage oligomeric matrix protein as a marker of osteoarthritis

Abstract

This study reports a simple and quantitative analytical method for detecting cartilage oligomeric matrix protein (COMP) using a lateral-flow immunoassay (LFI) format. An immuno-chromatographic assay was developed using a gold nanoparticle (AuNP)-conjugated monoclonal antibody (Ab) probe for the quantitative detection of COMP in human synovial fluid (SF). The detection antibody was conjugated with the AuNP (∼30 nm) to enable detection, and the capture antibody was immobilized within a multi-spot pattern in the test zone of a membrane strip. COMP in the human SF binds to the AuNP-conjugated detection antibody, and the COMP-Ab complex then binds to the capture antibody. The immunoassay test can be analyzed by visualizing the test strip with a commercial scanner and an imaging software program. The color density of the multi-spot pattern at the test zone increased in proportion to the concentration of COMP. The developed immunoassay exhibited a dynamic detection range from 0.6 to 20 μg/mL of COMP. The detection limit of the proposed LFI system was approximately 0.2 μg/mL. The test results showed good correlation with those obtained using a conventional enzyme-linked immunosorbent assay (ELISA) to detect COMP. We expect that the proposed immunoassay method, based on the quantification of COMP, is suitable for osteoarthritis diagnosis using SF samples.

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References

  1. 1.

    Posthuma-Trumpie, G.A., Korf, J. & Amerongen, A.V. Lateral flow (immuno) assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal. Bioanal. Chem. 393, 569–582 (2009).

    Article  CAS  Google Scholar 

  2. 2.

    Li, Z. et al. Rapid and sensitive detection of protein biomarker using a portable fluorescence biosensor based on quantum dots and a lateral flow test strip. Anal. Chem. 82, 7008–7014 (2010).

    Article  CAS  Google Scholar 

  3. 3.

    Yoon, C.H. et al. Development of a membrane strip immunosensor utilizing ruthenium as an electro-chemiluminescent signal generator. Biosens. Bioelectron. 19, 289–296 (2003).

    Article  CAS  Google Scholar 

  4. 4.

    Kim, J.-H. et al. Conductimetric membrane strip immunosensor with polyaniline-bound gold colloids as signal generator. Biosens. Bioelectron. 14, 907–915 (2000).

    Article  CAS  Google Scholar 

  5. 5.

    Tseng, S., Reddi, A.H. & Cesare, P.E.D. Cartilage oligomeric matrix protein (COMP): A biomarker of arthritis. Biomark. Insights. 4, 33–44 (2009).

    CAS  Google Scholar 

  6. 6.

    Rousseau, J.C. & Delmas, P.D. Biological markers in osteoarthritis. Nat. Clin. Pract. Rheumatol. 3, 346–356 (2007).

    Article  CAS  Google Scholar 

  7. 7.

    Vilim, V. et al. Serum cartilage oligomeric matrix protein reflects the presence of clinically diagnosed synovitis in patients with knee osteoarthritis. Osteoarthr. Cartil. 9, 612–618 (2001).

    Article  CAS  Google Scholar 

  8. 8.

    Bauer, D.C. et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthr. Cartil. 14, 723–727 (2006).

    Article  CAS  Google Scholar 

  9. 9.

    Song, S.Y. et al. Chip-based cartilage oligomeric matrix protein detection in serum and synovial fluid for osteoarthritis diagnosis. Anal. Biochem. 420, 139–146 (2012).

    CAS  Google Scholar 

  10. 10.

    Chandler, J., Gurmin, T. & Robinson, N. The place of gold in rapid tests. IVD Technol. 6, 37–49 (2000).

    Google Scholar 

  11. 11.

    Haiss, W., Thanh, N.T.K., Aveyard, J. & Fernig, D.G. Determination of size and concentration of gold nanoparticles from UV-Vis spectra. Anal. Chem. 79, 4215–4221 (2007).

    Article  CAS  Google Scholar 

  12. 12.

    Zhou, Y. et al. Gold nanoparticle probe-based immunoassay as a new tool for tetrodotoxin detection in puffer fish tissues. Sensor. Actuat. B-Chem. 146, 368–372 (2010).

    Article  Google Scholar 

  13. 13.

    Zhou, Y. et al. Colloidal gold probe-based immunochromatographic assay for the rapid detection of brevetoxins in fishery product samples. Biosens. Bioelectron. 24, 2744–2747 (2009).

    Article  CAS  Google Scholar 

  14. 14.

    Woo, J.-R., Lim, D.-K. & Nam, J.-M. Minimally stable nanoparticle-based colorimetric assay for simple, rapid, and sensitive antibody structure and activity evaluation. Small 7, 648–655 (2011).

    Article  CAS  Google Scholar 

  15. 15.

    Jung, Y.L., Jung, C.H., Parab, H., Li, T. & Park, H.G. Direct colorimetric diagnosis of pathogen infections by utilizing thiol-labeled PCR primers and unmodified gold nanoparticles. Biosens. Bioelectron. 25, 1941–1946 (2010).

    Article  CAS  Google Scholar 

  16. 16.

    Anfossi, L. et al. Development and application of a quantitative lateral flow immunoassay for fumonisins in maize. Anal. Chim. Acta 682, 104–109 (2010).

    Article  CAS  Google Scholar 

  17. 17.

    Martinez, A.W., Phillips, S.T. & Whiteside, G.M. Three-dimensional microfluidic devices fabricated in layered paper and tape. Proc. Natl. Acad. Sci. U.S.A. 105, 19606–19611 (2008).

    Article  CAS  Google Scholar 

  18. 18.

    Mündermann, A., Dyrby, C.O., Andriacchi, T.P. & King, K.B. Serum concentration of cartilage oligomeric matrix protein (COMP) is sensitive to physiological cyclic loading in healthy adults. Osteoarthr. Cartil. 13, 34–38 (2005).

    Article  Google Scholar 

  19. 19.

    Saxne, T. & Heinegard, D. Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Rheumatology (Oxford) 31, 583–591 (1992).

    Article  CAS  Google Scholar 

  20. 20.

    Gibson, D.S. & Rooney, M.E. The human synovial fluid proteome: A key factor in the pathology of joint disease. Proteom. Clin. Appl. 1, 889–899 (2007).

    Article  CAS  Google Scholar 

  21. 21.

    Belcher, C., Yaqub, R., Fawthrop, F., Bayliss, M. & Doherty, M. Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees. Ann. Rheum. Dis. 56, 299–307 (1997).

    Article  CAS  Google Scholar 

  22. 22.

    Liao, H. et al. Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis. Arthritis Rheum. 50, 3792–3803 (2004).

    Article  CAS  Google Scholar 

  23. 23.

    Frens, G. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nat. Phys. Sci. 241, 20–22 (1973).

    CAS  Google Scholar 

  24. 24.

    Peng, Z. et al. A novel immunoassay based on the dissociation of immunocomplex and fluorescence quenching by gold nanoparticles. Anal. Chim. Acta 583, 40–44 (2007).

    Article  CAS  Google Scholar 

  25. 25.

    Choi, D.H. et al. A dual gold nanoparticle conjugatebased lateral flow assay (LFA) method for the analysis of troponin I. Biosens. Bioelectron. 25, 1999–2002 (2010).

    Article  CAS  Google Scholar 

  26. 26.

    Yan, Z. et al. Rapid quantitative detection of Yersinia pestis by lateral-flow immunoassay and up-converting phosphor technology-based biosensor. Sensor. Actuat. B-Chem. 119, 656–663 (2006).

    Article  Google Scholar 

  27. 27.

    Wang, S., Zhang, C., Wang, J. & Zhang, Y. Development of colloidal gold-based flow-through and lateralflow immunoassays for the rapid detection of the insecticide carbaryl. Anal. Chim. Acta 546, 161–166 (2005).

    Article  CAS  Google Scholar 

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Correspondence to Hyun C. Yoon.

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Hong, S.Y., Park, Y.M., Jang, Y.H. et al. Quantitative lateral-flow immunoassay for the assessment of the cartilage oligomeric matrix protein as a marker of osteoarthritis. BioChip J 6, 213–220 (2012). https://doi.org/10.1007/s13206-012-6303-4

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Keywords

  • Cartilage oligomeric matrix protein
  • Lateralflow immunoassay
  • Osteoarthritis
  • Synovial fluid
  • Quantitative rapid kit