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Clinical validation of surface-enhanced Raman scattering-based immunoassays in the early diagnosis of rheumatoid arthritis

Abstract

We assessed the clinical feasibility of conducting immunoassays based on surface-enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group (n = 31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group (n = 43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (Grant Numbers 2008-0061856 and 2009-00426) and by the Nano Materials Technology Development Program through the National Research Foundation of Korea. The study was funded by the Ministry of Education, Science and Technology (Grant Number 2012M3A7B4035288). H.C. acknowledges the financial support (Grant Number 2013R1A1A2063269) of the National Research Foundation of Korea.

Conflict of interest

The authors declare that they have no competing interests.

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Correspondence to Jaebum Choo.

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Published in the topical collection Raman4Clinics with guest editors Jürgen Popp and Christoph Krafft.

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Chon, H., Wang, R., Lee, S. et al. Clinical validation of surface-enhanced Raman scattering-based immunoassays in the early diagnosis of rheumatoid arthritis. Anal Bioanal Chem 407, 8353–8362 (2015). https://doi.org/10.1007/s00216-015-9020-8

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  • DOI: https://doi.org/10.1007/s00216-015-9020-8

Keywords

  • Surface-enhanced Raman scattering
  • Anti-CCP
  • Rheumatoid arthritis
  • Immunoassay
  • Early diagnosis