Biomedical Microdevices

, Volume 16, Issue 5, pp 673–679 | Cite as

A sandwich substrate for ultrasensitive and label-free SERS spectroscopic detection of folic acid / methotrexate

  • Jing Yang
  • Xuebin Tan
  • Wei-Chuan Shih
  • Mark Ming-Cheng Cheng


A highly sensitive surface enhanced Raman scattering (SERS) substrate with particle-film sandwich geometry has been developed for the label free detection of folic acid (FA) and methotrexate (MTX). In this sandwich structure, the bottom layer is composed of a copper foil decorated with silver nanoparticles synthesized by the galvanic displacement reaction, and top layer is constituted by silver nanoparticles. The FA and MTX molecules are sandwiched between the silver nanoparticles decorated copper film and the silver nanoparticles. The plasmonic coupling between the two layers of the sandwich structure greatly enhances the SERS spectra of FA and MTX. SERS activity of the substrate was studied and optimized by adjusting the time of galvanic displacement reaction. The SERS spectra of the FA and MTX showed the minimum detection concentration of 100 pM. The identification of methotrexate and folic acid analogs was also carried out by SERS spectra analysis.


Surface enhanced Raman scattering (SERS) Folic acid Methotrexate 



This work was supported by NSF CAREER Award (1055932) MRI Award (1229635) and Wayne State University. We thank Dr. Da Deng for the help of UV-vis absorption spectroscopy measurement.

Supplementary material

10544_2014_9871_MOESM1_ESM.docx (167 kb)
Figure S1 (DOCX 167 kb)
10544_2014_9871_MOESM2_ESM.docx (144 kb)
Figure S2 (DOCX 144 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jing Yang
    • 1
  • Xuebin Tan
    • 1
  • Wei-Chuan Shih
    • 2
  • Mark Ming-Cheng Cheng
    • 1
  1. 1.Department of Electrical and Computer EngineeringWayne State UniversityDetroitUSA
  2. 2.Department of Electrical and Computer EngineeringThe University of HoustonHoustonUSA

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