, Volume 8, Issue 1, pp 3–12 | Cite as

Reading Biochips by Raman and Surface-Enhanced Raman Spectroscopies

  • Keren Kantarovich
  • Inbal Tsarfati-BarAd
  • Levi A. Gheber
  • Karsten Haupt
  • Ilana BarEmail author


Biochips are a rapidly increasing research field, driven by the versatility of sensing devices and the importance of their applications. The regular approaches for creating biochips and for reading them suffer from some limitations, motivating development of miniature biochips and label-free formats. To push forward these challenges, we have chosen to combine the methods of printing of droplets of synthetic receptors by pipettes or nanofountain pens with detection by Raman spectroscopy or its surface-assisted plasmon variant, namely, surface-enhanced Raman spectroscopy (SERS). The selected receptors included molecularly imprinted polymers (MIPs), produced by polymerization of functional and cross-linking monomers around a molecular template, the β-blocking drug propranolol. The measured Raman and SERS spectra of the MIP constituents enabled identification of the template presence and consequently chemical imaging of individual and multiple dots in an array. This concept, combining nanolithography techniques with SERS paves the road toward miniaturized arrayed MIP sensors with label-free, specific and quantitative molecular recognition.


Raman Surface-enhanced Raman spectroscopy Molecularly imprinted polymers Biochips Nanofountain pen 



KH and LAG gratefully acknowledge financial support from the European Union (MENDOS project, grant no. QLK4-CT2002-02323, Marie Curie Research Training Network NASCENT, grant no. MRTN-CT-2006-33873). IB thanks the James Franck Binational German–Israeli Program in Laser–Matter Interaction.


  1. 1.
    Vo-Dinh T (2005) In: Thompson RB (ed) Fluorescence sensors and biosensors. CRC Taylor & Francis, Boca RatonGoogle Scholar
  2. 2.
    Vo-Dinh T, Cullum B (2000) Biosensors and biochips: advances in biological and medical diagnostics. Fresenius J Anal Chem 366:540–551CrossRefGoogle Scholar
  3. 3.
    Lynch M, Mosher C, Huff J, Nettikadan S, Johnson J, Henderson E (2004) Functional protein nanoarrays for biomarker profiling. Proteomics 4:1695–1702CrossRefGoogle Scholar
  4. 4.
    Espina V, Mehta AI, Winters ME, Calvert V, Wulfkuhle J, Petricoin EF, Liotta LA (2003) Protein microarrays: molecular profiling technologies for clinical specimens. Proteomics 3:2091–2100CrossRefGoogle Scholar
  5. 5.
    Becker T, Hitzmann B, Muffler K, Poertner R, Reardon KF, Stahl F, Ulber R (2007) Future aspects of bioprocess monitoring. Ulber R, Sell (eds.) In: White biotechnology, advances in biochemical engineering–biotechnology, vol 105, pp 249–229Google Scholar
  6. 6.
    Sassolas A, Leca-Bouvier BD, Blum LJ (2008) DNA biosensors and microarrays. Chem Rev 108:109–139CrossRefGoogle Scholar
  7. 7.
    Borisov SM, Wolfbeis OS (2008) Optical biosensors. Chem Rev 108:423–461CrossRefGoogle Scholar
  8. 8.
    Bui BTS, Haupt K (2010) Molecularly imprinted polymers: synthetic receptors in bioanalysis. Anal Bioanal Chem 398:2481–2492CrossRefGoogle Scholar
  9. 9.
    Haupt K, Mosbach K (2000) Molecularly imprinted polymers and their use in biomimetic sensors. Chem Rev 100:2495–2504CrossRefGoogle Scholar
  10. 10.
    Mosbach K, Ramstrom O (1996) The emerging technique of molecular imprinting and its future impact on biotechnology. Bio-Technol 14:163–170CrossRefGoogle Scholar
  11. 11.
    Wulff G (2002) Enzyme-like catalysis by molecularly imprinted polymers. Chem Rev 102:1–27CrossRefGoogle Scholar
  12. 12.
    Tokonami S, Shiigi H, Nagaoka T (2009) Microl- and nanosized molecularly imprinted polymers for high-throughput analytical applications. Anal Chim Acta 641:7–13CrossRefGoogle Scholar
  13. 13.
    Moreno-Bondi MC, Fernando N-V, Elena B-P, Urraca JL (2008) Molecularly imprinted polymers as selective recognition elements in optical sensing. Curr Anal Chem 4:316–340CrossRefGoogle Scholar
  14. 14.
    Nelson DL, Cox MM (2000) Lehninger principles of biochemistry 3/e version. Freeman, New YorkGoogle Scholar
  15. 15.
    Conrad PG II, Nishimura PT, Aherne D, Schwartz BJ, Wu D, Fang N, Zhang X, Roberts MJ, Shea KJ (2003) Functional molecularly imprinted polymer microstructures fabricated using microstereolithography. Adv Mater 15:1541–1544CrossRefGoogle Scholar
  16. 16.
    Vandevelde F, Leïchlé T, Ayela C, Bergaud C, Nicu L, Haupt K (2007) Hierarchically nanostructured polymer films based on molecularly imprinted surface-bound nanofilaments. Langmuir 23:6490–6493CrossRefGoogle Scholar
  17. 17.
    Belmont A-S, Sokuler M, Haupt K, Gheber LA (2007) Direct writing of molecularly imprinted microstructures using a nanofountain pen. Appl Phys Lett 90:193101CrossRefGoogle Scholar
  18. 18.
    Henry OYF, Piletsky SA, Cullen DC (2008) Fabrication of molecularly imprinted polymer microarray on a chip by mid-infrared laser pulse initiated polymerisation. Biosens Bioelectron 23:1769–1775CrossRefGoogle Scholar
  19. 19.
    Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene-expression patterns with a complementary-DNA microarray. Science 270:467–470CrossRefGoogle Scholar
  20. 20.
    Campas M, Katakis I (2004) DNA biochip arraying, detection and amplification strategies. Trends Anal Chem 23:49–62CrossRefGoogle Scholar
  21. 21.
    Lewis A, Kheifetz Y, Shambrodt E, Radko A, Khatchatryan E, Sukenik C (1999) Fountain pen nanochemistry: atomic force control of chrome etching. Appl Phys Lett 75:2689–2691CrossRefGoogle Scholar
  22. 22.
    Long DA (1977) Raman spectroscopy. McGraw-Hill, USAGoogle Scholar
  23. 23.
    Fleischman M, Hendra PJ, McQuillan AJ (1974) Raman-spectra of pyridine adsorbed at a silver electrode. Chem Phys Lett 26:163–166CrossRefGoogle Scholar
  24. 24.
    Jeanmaire DL, Vanduyne RP (1977) Surface Raman spectroelectrochemistry.1. Heterocyclic, aromatic, and aliphatic-amines adsorbed on anodized silver electrode. J Electroanal Chem 84:1–20CrossRefGoogle Scholar
  25. 25.
    Kantarovich K, Belmont A-S, Haupt K, Bar I, Gheber LA (2009) Detection of template binding to molecularly imprinted polymers by Raman microspectroscopy. Appl Phys Lett 94:194103CrossRefGoogle Scholar
  26. 26.
    Kantarovich K, Tsarfati I, Gheber LA, Haupt K, Bar I (2009) Writing droplets of molecularly imprinted polymers by nano fountain pen and detecting their molecular interactions by surface-enhanced Raman scattering. Anal Chem 81:5686–5690CrossRefGoogle Scholar
  27. 27.
    Kantarovich K, Tsarfati I, Gheber LA, Haupt K, Bar I (2010) Reading microdots of a molecularly imprinted polymer by surface-enhanced Raman spectroscopy. Biosens Bioelectr 26:809–814CrossRefGoogle Scholar
  28. 28.
    Andersson LI (1996) Application of molecular imprinting to the development of aqueous buffer and organic solvent based radioligand binding assays for (S)-propranolol. Anal Chem 68:111–117CrossRefGoogle Scholar
  29. 29.
    Brunauer S (1943) The adsorption of gases and vapors vol I—physical adsorption. Princeton University Press, New JerseyGoogle Scholar
  30. 30.
    Perney NMB, Baumber JJ, Zoorob ME, Charlton MDB, Mahnkopf S, Netti CM (2006) Tuning localized plasmons in nanostructured substrates for surface-enhanced Raman scattering. Opt Express 14:847–857CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Keren Kantarovich
    • 1
  • Inbal Tsarfati-BarAd
    • 2
  • Levi A. Gheber
    • 2
  • Karsten Haupt
    • 3
  • Ilana Bar
    • 1
    Email author
  1. 1.Department of PhysicsBen-Gurion University of the NegevBeer-ShevaIsrael
  2. 2.Department of Biotechnology EngineeringBen-Gurion University of the NegevBeer-ShevaIsrael
  3. 3.Compiègne University of Technology, UMR CNRS 6022CompiègneFrance

Personalised recommendations