Skip to main content

Advertisement

SpringerLink
Log in

Microfluidic Plasmonic Biosensor for Breast Cancer Antigen Detection

  • Published:
Plasmonics Aims and scope Submit manuscript

Abstract

Biosensors based on surface plasmon resonance (SPR), operating with the Kretschmann conventional arrangement, have been employed for biomolecular detection of tumor markers. However, the traditional SPR configuration presents some experimental inconveniences that are overcome by using plasmonic substrates based on nanohole arrays manufactured in metallic films. This SPR configuration exhibits the extraordinary optical transmission (EOT) phenomenon, which is explored in the monitoring of binding events that occur on the metal surface. In this work, we proposed a plasmon biosensor based on nanohole arrays built on gold film operating in collinear transmission mode by using spectral investigation for signal transduction. The SPR substrate was coupled to a microfluidic system and showed good sensitivity and linearity. A concentration of 30 ng mL−1 of human epidermal receptor protein-2 (HER2) antigen (associated with breast cancer) was detected using the integrated device; this showed its great potential to be used in tumor diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ebbesen TW, Lezec HJ, Ghaemi HF, Thio T, Wolff PA (1998) Extraordinary optical transmission through sub-wavelength hole arrays. Nature 391:667–669. doi:10.1038/35570

    Article  CAS  Google Scholar 

  2. Bethe HA (1944) Theory of diffraction by small holes. Phys Rev 66:163–182. doi:10.1103/PhysRev.66.163

    Article  Google Scholar 

  3. Homola J (2008) Surface plasmon resonance sensors for detection of chemical and biological species. Chem Rev (Washington, DC, U S) 108:462–493. doi:10.1021/cr068107d

    Article  CAS  Google Scholar 

  4. De Leebeeck A, Kumar LKS, De Lange V, Sinton D, Gordon R, Brolo AG (2007) On-chip surface-based detection with nanohole arrays. Anal Chem 79:4094–4100. doi:10.1021/ac070001a

    Article  CAS  Google Scholar 

  5. Gordon R, Sinton D, Kavanagh KL, Brolo AG (2008) A new generation of sensors based on extraordinary optical transmission. Acc Chem Res 41:1049–1057. doi:10.1021/ar800074d

    Article  CAS  Google Scholar 

  6. Monteiro JP, Carneiro LB, Rahman MM, Brolo AG, Santos MJL, Ferreira J, Girotto EM (2013) Effect of periodicity on the performance of surface plasmon resonance sensors based on subwavelength nanohole arrays. Sensors Actuators B 178:366–370. doi:10.1016/j.snb.2012.12.090

    Article  CAS  Google Scholar 

  7. Yanga JC, Ji J, Hoglea JM, Larson DN (2009) Multiplexed plasmonic sensing based on small-dimension nanohole arrays and intensity interrogation. Biosens Bioelectron 24:2334–2338. doi:10.1016/j.bios.2008.12.011

    Article  CAS  Google Scholar 

  8. Tellez GAC, Ahmed A, Gordon R (2012) Optimizing the resolution of nanohole arrays in metal films for refractive-index sensing. Appl Phys A Mater Sci Process 109:775–780. doi:10.1007/s00339-012-7405-5

    Article  CAS  Google Scholar 

  9. Kretschmann E, Raether HZ (1968) Radiative decay of nonradiative surface plasmons excited by light Z. Naturforsch 23A 23:2135–2136. doi: citeulike-article-id:3901347

  10. Patel PDJ (2006) Overview of affinity biosensors in food analysis. J AOAC Int 89:805

    CAS  Google Scholar 

  11. Lazcka O, Campo FJD, Munoz FX (2007) Pathogen detection: a perspective of traditional methods and biosensors. Biosens Bioelectron 22:1205–1217. doi:10.1016/j.bios.2006.06.036

    Article  CAS  Google Scholar 

  12. Leonard P, Hearty S, Brennan J, Dunne L, Quinn J, Chakraborty T, O’Kennedy R (2003) Advances in biosensors for detection of pathogens in food and water. Enzym Microb Technol 32:3–13. doi:10.1016/S0141-0229(02)00232-6

    Article  CAS  Google Scholar 

  13. Mello LD, Kubota LT (2002) Review of the use of biosensors as analytical tools in the food and drink industries. Food Chem 77:237–256. doi:10.1016/S0308-8146(02)00104-8

    Article  CAS  Google Scholar 

  14. Baeumner AJ (2003) Biosensors for environmental pollutants and food contaminants. Anal Bioanal Chem 377:434–445. doi:10.1007/s00216-003-2158-9

    Article  CAS  Google Scholar 

  15. Farre M, Martinez E, Ramon J, Navarro A, Radjenovic J, Mauriz E, Lechuga L, Marco MP, Barcelo D (2007) Part per trillion determination of atrazine in natural water samples by a surface plasmon resonance immunosensor. Anal Bioanal Chem 388:207–214. doi:10.1007/s00216-007-1214-2

    Article  CAS  Google Scholar 

  16. Shankaran DR, Matsumoto K, Toko K, Miura N (2006) Performance evaluation and comparison of four SPR immunoassays for rapid and label-free detection of TNT. Electrochemistry (Tokyo, Jpn) 74:141–144. doi:10.5796/electrochemistry.74.141

    Article  Google Scholar 

  17. Kim SJ, Gobi KV, Harada R, Shankaran DR, Miura N (2006) Miniaturized portable surface plasmon resonance immunosensor applicable for onsite detection of low-molecular-weight analytes. Sensors Actuators B 115:349–256. doi:10.1016/j.snb.2005.09.025

    Article  CAS  Google Scholar 

  18. Ock K, Jang G, Roh Y, Kim S, Kim J, Koh K (2001) Optical detection of Cu2+ ion using a SQ-dye containing polymeric thin-film on Au surface. Microchem J 70:301–305. doi:10.1016/S0026-265X(01)00133-3

    Article  CAS  Google Scholar 

  19. Soh N, Watanabe T, Asano Y, Imato T (2003) Indirect competitive immunoassay for bisphenol A based on a surface plasmon resonance sensor. Sens and Materials 15:423–438

    CAS  Google Scholar 

  20. Soh N, Tokuda T, Watanabe T, Mishima K, Imato T, Masadome T, Asano Y, Okutani S, Niwa O, Brown S (2003) A surface plasmon resonance immunosensor for detecting a dioxin precursor using a gold binding polypeptide. Talanta 60:733–745. doi:10.1016/S0039-9140(03)00139-5

    Article  CAS  Google Scholar 

  21. Shimomura M, Nomura Y, Zhang W, Sakino M, Lee KH, Ikebukuro K, Karube I (2001) Simple and rapid detection method using surface plasmon resonance for dioxins, polychlorinated biphenylx and atrazine. Anal Chim Acta 434:223–230. doi:10.1016/S0003-2670(01)00809-1

    Article  CAS  Google Scholar 

  22. Gobi KV, Iwasaka H, Miura N (2007) Self-assembled PEG monolayer based SPR immunosensor for label-free detection of insulin. Biosens Bioelectron 22:1382–1389. doi:10.1016/j.bios.2006.06.012

    Article  CAS  Google Scholar 

  23. Dillon PP, Daly SJ, Manning BM, O’Kennedy R (2003) Immunoassay for the determination of morphine-3-glucuronide using a surface plasmon resonance-based biosensor. Biosens Bioelectron 18:217–227. doi:10.1016/S0956-5663(02)00182-3

    Article  CAS  Google Scholar 

  24. Fitzpatrick B, O’Kennedy R (2004) The development and application of a surface plasmon resonance-based inhibition immunoassay for the determination of warfarin in plasma ultrafiltrate. J Immunol Methods 291:11–25. doi:10.1016/j.jim.2004.03.015

    Article  CAS  Google Scholar 

  25. Ladd J, Boozer C, Yu Q, Chen S, Homola J, Jiang S (2004) DNA-directed protein immobilization on mixed self-assembled monolayers via a streptavidin bridge. Langmuir 20:8090–8095. doi:10.1021/la049867r

    Article  CAS  Google Scholar 

  26. Chung JW, Bernhardt R, Pyun JC (2006) Sequential analysis of multiple analytes using a surface plasmon resonance (SPR) biosensor. J Immunol Methods 311:178–188. doi:10.1016/j.jim.2006.02.003

    Article  CAS  Google Scholar 

  27. Miyashita M, Shimada T, Miyagawa H, Akamatsu M (2005) Surface plasmon resonance-based immunoassay for 17beta-estradiol and its application to the measurement of estrogen receptor-binding activity. Anal Bioanal Chem 381:667–673. doi:10.1007/s00216-004-2952-z

    Article  CAS  Google Scholar 

  28. Cao C, Kim JP, Kim BW, Chae H, Yoon HC, Yang SS, Sim SJ (2006) A strategy for sensitivity and specificity enhancements in prostate specific antigen-alpha1-antichymotrypsin detection based on surface plasmon resonance. Biosens Bioelectron 21:2106–2113. doi:10.1016/j.bios.2005.10.014

    Article  CAS  Google Scholar 

  29. Li Y, Lee HJ, Corn RM (2007) Detection of protein biomarkers using RNA aptamer microarrays and enzymatically amplified surface plasmon resonance imaging. Anal Chem (Washington, DC, U S) 79:1082–1088. doi:10.1021/ac061849m

    Article  CAS  Google Scholar 

  30. Besselink GA, Kooyman RP, van Os PJ, Engbers GH, Schasfoort RB (2004) Signal amplification on planar and gel-type sensor surfaces in surface plasmon resonance-based detection of prostate-specific antigen. Anal Biochem 333:165–173. doi:10.1016/j.ab.2004.05.009

    Article  CAS  Google Scholar 

  31. Wu LP, Li YF, Huang CZ, Zhang Q (2006) Visual detection of Sudan dyes based on the plasmon resonance light scattering signals of silver nanoparticles. Anal Chem 78:5570–5577. doi:10.1021/ac0603577

    Article  CAS  Google Scholar 

  32. Chung JW, Bernhardt R, Pyun JC (2006) Additive assay of cancer marker CA 19-9 by SPR biosensor. Sensors Actuators B 118:28–32. doi:10.1016/j.snb.2006.04.015

    Article  CAS  Google Scholar 

  33. Yang CY, Brooks E, Li Y, Denny P, Ho CM, Qi FX, Shi WY, Wolinsky L, Wu B, Wong DTW, Montemagno CD (2005) Detection of picomolar levels of interleukin-8 in human saliva by SPR. Lab Chip 5:1017–1023. doi:10.1039/b504737d

    Article  CAS  Google Scholar 

  34. Tang DP, Yuan R, Chai YQ (2006) Novel immunoassay for carcinoembryonic antigen based on protein A-conjugated immunosensor chip by surface plasmon resonance and cyclic voltammetry. Bioprocess Biosyst Eng 28:315–321. doi:10.1007/s00449-005-0036-x

    Article  CAS  Google Scholar 

  35. Monfregola L, Vitale RM, Amodeo P, De Luca S (2009) A SPR strategy for high-throughput ligand screenings based on synthetic peptides mimicking a selected subdomain of the target protein: a proof of concept on HER2 receptor. Bioorg Med Chem 17:7015–7020. doi:10.1016/j.bmc.2009.08.004

    Article  CAS  Google Scholar 

  36. Hunta HK, Armani AM (2010) Label-free biological and chemical sensors. Nanoscale 2:1544–1559. doi:10.1039/c0nr00201a

    Article  CAS  Google Scholar 

  37. Escobedo C, Brolo AG, Gordon R, Sinton D (2010) Flow-through vs flow-over: analysis of transport and binding in nanohole array plasmonic biosensors. Anal Chem 82:10015–10020. doi:10.1021/ac101654f

    Article  CAS  Google Scholar 

  38. Ji J, O’Connell JG, Carter DJD, Larson DN (2008) High-throughput nanohole array based system to monitor multiple binding events in real time. Anal Chem 80:2491–2498. doi:10.1021/ac7023206

    Article  CAS  Google Scholar 

  39. Eftekhari F, Escobedo C, Ferreira J, Duan X, Girotto EM, Brolo AG, Gordon R, Sinton D (2009) Nanoholes as nanochannels: flow-through plasmonic sensing. Anal Chem 81:4308–4311. doi:10.1021/ac900221y

    Article  CAS  Google Scholar 

  40. Escobedo C, Chou Y-W, Rahman M, Duan X, Gordon R, Sinton D, Brolo AG, Ferreira J (2013) Quantification of ovarian cancer markers with integrated microfluidic concentration gradient and imaging nanohole surface plasmon resonance. Analyst 138:1450–1458. doi:10.1039/c3an36616b

    Article  CAS  Google Scholar 

  41. Basil CF, Zhao YD, Zavaglia K, Jin P, Panelli MC, Voiculescu S, Mandruzzato S, Lee HM, Seliger B, Freedman RS, Taylor PR, Hu N, Zanovello P, Marincola FM, Wang E (2006) Common cancer biomarkers. Cancer Res 66:2953–2961. doi:10.1158/0008-5472.CAN-05-3433

    Article  CAS  Google Scholar 

  42. Esteva FJ, Cheli CD, Fritsche H, Fornier M, Slamon D, Thiel RP, Luftner D, Ghani F (2005) Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies. Breast Cancer Res 7:R436–R443. doi:10.1186/bcr1020

    Article  CAS  Google Scholar 

  43. Coussens L, Yang-Feng TL, Lioa YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, Levinson A, Ullrich A (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230:1132–1139. doi:10.1126/science.2999974

    Article  CAS  Google Scholar 

  44. Schecter AL, Stern DF, Vaidyanathan L, Decker SJ, Drebin JA, Greene MI, Weinberg AR (1984) The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 312:513–516. doi:10.1038/312513a0

    Article  Google Scholar 

  45. Slamon DJ, Goldolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712. doi:10.1126/science.2470152

    Article  CAS  Google Scholar 

  46. Gown AM (2008) Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol 21:S8–S15. doi:10.1038/modpathol.2008.34

    Article  CAS  Google Scholar 

  47. Freitas CS (2008) Estendendo o Conhecimento sobre a Família Her-Receptores para o Fator de Crescimento Epidérmico e seus ligantes às Malignidades Hematológicas. Revista Brasileira de Cancerologia 54:79–86

    Google Scholar 

  48. Carneiro LB, Ferreira J, Santos MJL, Monteiro JP, Girotto EM (2011) A new approach to immobilize poly (vinyl alcohol) on poly (dimethylsiloxane) resulting in low protein adsorption. Appl Surf Sci 257:10514–10519. doi:10.1016/j.apsusc.2011.07.031

    Article  CAS  Google Scholar 

  49. Huang NP, Voros J, De Paul SM, Textor M, Spencer ND (2002) Biotin-derivatized poly (L-lysine)-g-poly (ethylene glycol): a novel polymeric interface for bioaffinity sensing. Langmuir 18:220–230. doi:10.1021/la010913m

    Article  CAS  Google Scholar 

  50. Marie E, Dahlin AB, Tegenfeldt JO, Hook F (2007) Generic surface modification strategy for sensing applications based on AuSiO2 nanostructures. Biointerphases 2:49–55. doi:10.1116/1.2717926

    Article  CAS  Google Scholar 

  51. Fei X, Guoliang Z, Marcus T, Wolfgang K (2006) Surface plasmon optical detection of beta-lactamase binding to different interfacial matrices combined with fiber optic absorbance spectroscopy for enzymatic activity assays. Biointerphases 1:73–81. doi:10.1116/1.2219109

    Article  CAS  Google Scholar 

  52. Knoll W, Liley M, Piscevic D, Spinke J, Tarlov MJ (1997) Supramolecular architectures for the functionalization of solid surfaces. Adv Biophys 34:231–251. doi:10.1016/S0065-227X(97)89642-6

    Article  CAS  Google Scholar 

  53. Homola J, Yee SS, Gauglitz G (1999) Surface plasmon resonance sensors: review. Sensors Actuators B 54:3–15. doi:10.1016/S0925-4005(98)00321-9

    Article  CAS  Google Scholar 

  54. Novotny L, Hecht B (2006) Principles of nano-optics. Cambridge University Press, Cambridge

    Book  Google Scholar 

  55. Pang L, Hwang GM, Slutsky B, Fainman Y (2007) Spectral sensitivity of two-dimensional nanohole array surface plasmon polariton resonance sensor. Appl Phys Lett 91:123112. doi:10.1063/1.2789181

    Article  CAS  Google Scholar 

  56. Eftekhari F, Escobedo C, Ferreira J, Duan X, Girotto EM, Brolo AG, Gordon R, Sinton D (2009) Nanoholes as nanochannels: flow-through plasmonic sensing. Anal Chem 81:4308–4311. doi:10.1021/ac900221y

    Article  CAS  Google Scholar 

  57. Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R, Lee H (2014) Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol 32:490–498. doi:10.1038/nbt.2886

    Article  CAS  Google Scholar 

  58. Zayats AV, Smolyaninov II, Maradudin AA (2005) Nano-optics of surface plasmon polaritons. Phys Rep 408:131–314. doi:10.1016/j.physrep.2004.11.001

    Article  CAS  Google Scholar 

  59. Meenakshi A, Kumar RS, Kumar NS (2002) ELISA for quantitation of serum C-erbB-2 oncoprotein in breast cancer patients. J Immunoassay Immunochem 23:293–305. doi:10.1081/IAS-120013028

    Article  CAS  Google Scholar 

Download references

Acknowledgments

J. P. Monteiro thanks CAPES for the fellowship. We gratefully acknowledge Fundação Araucária (process no. 209/2014) and CNPq (process no. 473213/2011-7) for financial support.

Author information

Author notes

  1. Johny Paulo Monteiro

    Present address: Department of Chemistry, Universidade Tecnológica Federal do Paraná - UTFPR, Marcílio Dias Street, 635, 86812-460, Apucarana, PR, Brazil

Authors and Affiliations

  1. Materials Chemistry and Sensors Laboratories, Department of Chemistry, State University of Maringá, Av Colombo 5790, 87020-900, Maringá, PR, Brazil

    Johny Paulo Monteiro, Jean Halison de Oliveira, Eduardo Radovanovic & Emerson Marcelo Girotto

  2. Department of Chemistry, University of Victoria, P.O. Box 3065, V8W 3 V6, Victoria, British Columbia, Canada

    Alexandre Guimarães Brolo

Authors
  1. Johny Paulo Monteiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean Halison de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eduardo Radovanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandre Guimarães Brolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emerson Marcelo Girotto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Johny Paulo Monteiro.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Monteiro, J.P., de Oliveira, J.H., Radovanovic, E. et al. Microfluidic Plasmonic Biosensor for Breast Cancer Antigen Detection. Plasmonics 11, 45–51 (2016). https://doi.org/10.1007/s11468-015-0016-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11468-015-0016-1

Keywords

Search

Navigation