Abstract
In this work, we developed a SERS platform for quantitative detection of carcinoembryonic antigen (CEA) in serum of patients with colorectal cancers. Anti-CEA-functionalized 4-mercaptobenzoic acid–labeled Au/Ag core-shell bimetallic nanoparticles were prepared first and then used to analyze CEA antigen solutions of different concentrations. A calibration curve was established in the range from 5 × 10−3 to 5 × 105 ng/mL. Finally, this new SERS probe was applied for quantitative detection of CEA in serum obtained from 26 colorectal cancer patients according to the calibration curve. The results were in good agreement with that obtained by electrochemical luminescence method, suggesting that SERS immunoassay has high sensitivity and specificity for CEA detection in serum. A detection limit of 5 pg/ml was achieved. This study demonstrated the feasibility and great potential for developing this new technology into a clinical tool for analysis of tumor markers in the blood.
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A. Jemal, F. Bray, M. Center, J. Ferlay, E. Ward, D. Forman, Global cancer statistics. CA Cancer J. Clin. 61, 69–90 (2011)
R. Siegel, E. Ward, O. Brawley, A. Jemal, Cancer statistics, 2011. CA Cancer J. Clin. 61, 212–236 (2011)
M. Center, A. Jemal, E. Ward, International trends in colorectal cancer incidence rates. Cancer Epidemiol. Biomark. Prev. 18, 1688–1694 (2009)
R.M. McLoughlin, C.A. O’Morain, Colorectal cancer screening. World J. Gastroenterol. 12, 6747–6750 (2006)
R. Labianca, G. Beretta, S. Mosconi, L. Milesi, M. Pessi, Colorectal cancer: screening. An. Oncol. 16, 127–132 (2005)
M.J. Duffy, Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin. Chem. 47, 624–630 (2001)
R.A. Alvarez-Puebla, L.M. Liz-Marza, SERS-Based diagnosis and biodetection. Small 6, 604–610 (2010)
J. Kneipp, H. Kneipp, K. Kneipp, SERS—a single-molecule and nanoscale tool for bioanalytics. Chem. Soc. Rev. 37, 1052–1060 (2008)
Y.S. Huh, A.J. Chung, D. Erickson, Surface enhanced Raman spectroscopy and its application to molecular and cellular analysis. Microfluid. Nanofluid. 6, 285–297 (2009)
S. Hudson, G. Chumanov, Bioanalytical applications of SERS (surface-enhanced Raman spectroscopy). Anal. Bioanal. Chem. 394, 679–686 (2009)
D. Graham, R. Goodacre, Chemical and bioanalytical applications of surface enhanced Raman scattering spectroscopy. Chem. Soc. Rev. 37, 883–884 (2008)
K.C. Bantz, A.F. Meyer, N.J. Wittenberg, H. Im, Kurtulu, S.H. Lee, N.C. Lindquist, S.H. Oh, C.L. Haynes, Recent progress in SERS biosensing. Phys. Chem. Chem. Phys 13, 11551–11567 (2011)
S. Xu, X. Ji, W. Xu, B. Zhao, X. Dou, Y. Bai, Y. Ozaki, Surface-enhanced Raman scattering studies on immunoassay. J Biomed Opt 10, 031112 (2005)
B. Lutz, C. Dentinger, L. Nguyen, L. Sun, J. Zhang, A. Allen, S. Chan, B. Knudsen, Spectral analysis of multiplex Raman probe signatures. ACS Nano 2, 2306–2314 (2008)
Y. Cao, R. Jin, C. Mirkin, Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297, 1536 (2002)
M. Culha, D. Stokes, L.R. Allain, T. Vo-Dinh, Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics. Anal. Chem. 75, 6196–6201 (2003)
R.J. Stokes, A. Macaskill, J.A. Dougan, P.G. Hargreaves, H.M. Stanford, W.E. Smith, K. Faulds, D. Graham, Highly sensitive detection of dye-labelled DNA using nanostructured gold surfaces. Chem. Commun. 27, 2811–2813 (2007)
J.J. Storhoff, A.D. Lucas, V. Garimella, Y.P. Bao, U.R. Müller, Homogeneous detection of unamplified genomic DNA sequences based on colorimetric scatter of gold nanoparticle probes. Nat. Biotechnol. 22, 883 (2004)
T. Vo-Dinh, L.R. Allain, D.L. Stokes, Cancer gene detection using surface-enhanced Raman scattering (SERS). J. Raman Spectrosc. 33, 511–516 (2002)
J.W. Chen, Y. Lei, X.J. Liu, J.H. Jiang, G.L. Shen, R.Q. Yu, Immunoassay using surface-enhanced Raman scattering based on aggregation of reporter-labeled immunogold nanoparticles. Anal. Bioanal. Chem. 392, 187–193 (2008)
B. Du, Z. Li, Y. Cheng, Homogeneous immunoassay based on aggregation of antibody-functionalized gold nanoparticles coupled with light scattering detection. Talanta 75, 959–964 (2008)
X. Ji, S. Xu, L. Wang, M. Liu, K. Pan, H. Yuan, L. Ma, W. Xu, J. Li, Y. Bai, Immunoassay using the probe-labeled Au/Ag core-shell nanoparticles based on surface-enhanced Raman scattering. Colloids Surf. A Physicochem. Eng. Asp. 257, 171–175 (2005)
C. Lin, Y. Yang, Y. Chen, T. Yang, H. Chang, A new protein A assay based on Raman reporter labeled immunogold nanoparticles. Biosens. Bioelectron. 24, 178–183 (2008)
B. Lutz, C. Dentinger, L. Sun, L. Nguyen, J. Zhang, A. Chmura, A. Allen, S. Chan, B. Knudsen, Raman nanoparticle probes for antibody-based protein detection in tissues. J. Histochem. Cytochem. 56, 371–379 (2008)
S. Schlücker, B. Küstner, A. Punge, R. Bonfig, A. Marx, P. Ströbel, Immuno-Raman microspectroscopy: in situ detection of antigens in tissue specimens by surface-enhanced Raman scattering. J. Raman Spectrosc. 37, 719–721 (2006)
L. Sun, K. Sung, C. Dentinger, B. Lutz, L. Nguyen, J. Zhang, H. Qin, M. Yamakawa, M. Cao, Y. Lu, Composite organic-inorganic nanoparticles as Raman labels for tissue analysis. Nano Lett. 7, 351–356 (2007)
K.K. Maiti, U. Dinish, C.Y. Fu, J.J. Lee, K.S. Soh, S.W. Yun, R. Bhuvanaeswari, M. Olivo, Y.T. Chang, Development of biocompatible SERS nanotag with increased stability by chemisorption of reporter molecule for in vivo cancer detection. Biosens. Bioelectron. 26, 398–403 (2010)
A. Pallaoro, G. Braun, N. Reich, M. Moskovits, Mapping local pH in live cells using encapsulated fluorescent SERS nanotags. Small 6, 618–622 (2010)
X. Qian, X.H. Peng, D.O. Ansari, Q. Yin-Goen, G.Z. Chen, D.M. Shin, L. Yang, A.N. Young, M.D. Wang, S. Nie, In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat. Biotechnol. 26, 83–90 (2007)
M.Y. Sha, H. Xu, M.J. Natan, R. Cromer, Surface-enhanced Raman scattering tags for rapid and homogeneous detection of circulating tumor cells in the presence of human whole blood. J. Am. Chem. Soc. 130, 17214–17215 (2008)
D. Lin, S. Feng, J. Pan, Y. Chen, J. Lin, G. Chen, S. Xie, H. Zeng, R. Chen, Colorectal cancer detection by gold nanoparticle based surface-enhanced Raman spectroscopy of blood serum and statistical analysis. Opt. Express 19, 13565–13577 (2011)
Y. Yang, J. Shi, G. Kawamura, M. Nogami, Preparation of Au-Ag, Ag-Au core-shell bimetallic nanoparticles for surface-enhanced Raman scattering. Scr. Mater. 58, 862–865 (2008)
Y. Chen, X. Zheng, G. Chen, C. He, W. Zhu, S. Feng, G. Xi, R. Chen, F. Lan, H. Zeng, Immunoassay for LMP1 in nasopharyngeal tissue based on surface-enhanced Raman scattering. Int. J. Nanomed. 7, 73 (2012)
L.A. Chrisey, G.U. Lee, C.E. O’Ferrall, Covalent attachment of synthetic DNA to self-assembled monolayer films. Nucleic Acids Res. 24, 3031–3039 (1996)
J. Zhao, H. Lui, D. McLean, H. Zeng, Automated autofluorescence background subtraction algorithm for biomedical Raman spectroscopy. Appl. Spectrosc. 61, 1225–1232 (2007)
Acknowledgments
We thank Jing Wang and Gangqin Xi for excellent technical assistance. This work was supported by the National Natural Science Foundation of China (No. 61210016, 61178090, 81101110), the Canadian Institutes of Health Research International Scientific Exchange Program, the Natural Science Foundation of Fujian Province (No.2012J01326), and the Medical Innovation Program of Fujian Province (No.2012-CX-7).
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Chen, G., Chen, Y., Zheng, X. et al. Surface-enhanced Raman scattering study of carcinoembryonic antigen in serum from patients with colorectal cancers. Appl. Phys. B 113, 597–602 (2013). https://doi.org/10.1007/s00340-013-5515-1
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DOI: https://doi.org/10.1007/s00340-013-5515-1