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Journal of RF-Engineering and Telecommunications

Editor-in-Chief: Jakoby, Rolf

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Volume 72, Issue 3-4


Germanium Plasmon Enhanced Resonators for Label-Free Terahertz Protein Sensing

Maximilian Bettenhausen
  • Electrical Engineering/Computer Science Dept. and CINSaT, University of Kassel, Kassel, Germany
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/ Friedhard Römer
  • Electrical Engineering/Computer Science Dept. and CINSaT, University of Kassel, Kassel, Germany
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/ Bernd Witzigmann
  • Corresponding author
  • Electrical Engineering/Computer Science Dept. and CINSaT, University of Kassel, Kassel, Germany
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/ Julia Flesch / Rainer Kurre / Sergej Korneev / Jacob Piehler / Changjiang You / Marcin Kazmierczak / Subhajit Guha / Giovanni Capellini / Thomas Schröder
Published Online: 2018-03-07 | DOI: https://doi.org/10.1515/freq-2018-0009


A Terahertz protein sensing concept based on subwavelength Ge resonators is presented. Ge bowtie resonators, compatible with CMOS fabrication technology, have been designed and characterized with a resonance frequency of 0.5 THz and calculated local intensity enhancement of 10.000. Selective biofunctionalization of Ge resonators on Si wafer was achieved in one step using lipoic acid-HaloTag ligand (LA-HTL) for biofunctionalization and passivation. The results lay the foundation for future investigation of protein tertiary structure and the dynamics of protein hydration shell in response to protein conformation changes.

This article offers supplementary material which is provided at the end of the article.

Keywords: terahertz sensor; protein conformation; semiconductor plasmonics


  • [1]

    H.-J. Wu, et al., “Membrane-protein binding measured with solution-phase plasmonic nanocube sensors,” Nat. Methods, vol. 9, pp. 1189, 2012.CrossrefWeb of ScienceGoogle Scholar

  • [2]

     M. Bhagawati, C. You, and J. Piehler, “Quantitative real-time imaging of protein–Protein interactions by LSPR detection with micropatterned gold nanoparticles,” Anal. Chem., vol. 85, no. 20, pp. 9564–9571, 2013.Web of ScienceCrossrefGoogle Scholar

  • [3]

    A. Tsuboi, K. Nakamura, and N. Kobayashi, “A localized surface plasmon resonance-based multicolor electrochromic device with electrochemically size-controlled silver nanoparticles,” Advanced Mater., vol. 25, no. 23, pp. 3197–3201, 2013.CrossrefWeb of ScienceGoogle Scholar

  • [4]

    P. Chen, et al., “Multiplex serum cytokine immunoassay using nanoplasmonic biosensor microarrays,” ACS Nano, vol. 9, no. 4, pp. 4173–4181, 2015.CrossrefWeb of ScienceGoogle Scholar

  • [5]

    Y. Song, et al., “AC electroosmosis-enhanced nanoplasmofluidic detection of ultralow-concentration cytokine,” Nano Lett., vol. 17, no. 4, pp. 2374–2380, 2017.CrossrefWeb of ScienceGoogle Scholar

  • [6]

     G. Klenkar, et al., “Piezo dispensed microarray of multivalent chelating thiols for dissecting complex protein-protein interactions,” Anal. Chem., vol. 78, pp. 3643–3650, 2006.CrossrefGoogle Scholar

  • [7]

     M. Piliarik, M. Bockova, and J. Homola, “Surface plasmon resonance biosensor for parallelized detection of protein biomarkers in diluted blood plasma,” Biosens Bioelectron, vol. 26, no. 4, pp. 1656–1661, 2010.Web of ScienceCrossrefGoogle Scholar

  • [8]

    X. Yu, D. Xu, and Q. Cheng, “Label-free detection methods for protein microarrays,” Proteomics, vol. 6, no. 20, pp. 5493–5503, 2006.CrossrefGoogle Scholar

  • [9]

    T. Kumeria, et al., “Label-free reflectometric interference microchip biosensor based on nanoporous alumina for detection of circulating tumour cells,” Biosens. Bioelectron., vol. 35, no. 1, pp. 167–173, 2012.Web of ScienceCrossrefGoogle Scholar

  • [10]

     G. Gauglitz, “Multiple reflectance interference spectroscopy measurements made in parallel for binding studies,” Rev. Sci. Instruments, vol. 76, no. 6, pp. 062224, 2005.CrossrefGoogle Scholar

  • [11]

    R. Adato, et al., “Ultra-sensitive vibrational spectroscopy of protein monolayers with plasmonic nanoantenna arrays,” Proc. Natl. Acad. Sci., vol. 106, no. 46, pp. 19227–19232, 2009.CrossrefGoogle Scholar

  • [12]

    X. Jiang, et al., “Resolving voltage-dependent structural changes of a membrane photoreceptor by surface-enhanced IR difference spectroscopy,” Proc. Natl. Acad. Sci., vol. 105, no. 34, pp. 12113–12117, 2008.CrossrefGoogle Scholar

  • [13]

    K. Ataka, S. T. Stripp, and J. Heberle, “Surface-enhanced infrared absorption spectroscopy (SEIRAS) to probe monolayers of membrane proteins,” Biochimica Et Biophysica Acta (BBA) - Biomembranes, vol. 1828, no. 10, pp. 2283–2293, 2013.Web of ScienceCrossrefGoogle Scholar

  • [14]

    D. Rodrigo, et al., “Mid-infrared plasmonic biosensing with graphene,” Science, vol. 349, no. 6244, pp. 165–168, 2015.CrossrefWeb of ScienceGoogle Scholar

  • [15]

    R. Balu, et al., “Terahertz spectroscopy of bacteriorhodopsin and rhodopsin: similarities and differences,” Biophys. J., vol. 94, no. 8, pp. 3217–3226, 2008.Web of ScienceCrossrefGoogle Scholar

  • [16]

    S. E. Whitmire, et al., “Protein flexibility and conformational state: A comparison of collective vibrational modes of wild-type and D96N bacteriorhodopsin,” Biophys. J., vol. 85, no. 2, pp. 1269–1277, 2003.CrossrefGoogle Scholar

  • [17]

    S. Ebbinghaus, et al., “An extended dynamical hydration shell around proteins,” Proc. Natl. Acad. Sci. U.S.A., vol. 104, no. 52, pp. 20749–20752, 2007.CrossrefGoogle Scholar

  • [18]

    D. M. Leitner, M. Gruebele, and M. Havenith, “Solvation dynamics of biomolecules: Modeling and terahertz experiments,” Hfsp J, vol. 2, no. 6, pp. 314–323, 2008.Web of ScienceCrossrefGoogle Scholar

  • [19]

    S. Ebbinghaus, et al., “Protein sequence- and pH-dependent hydration probed by terahertz spectroscopy,” J. Am. Chem. Soc., vol. 130, no. 8, pp. 2374–2375, 2008.CrossrefWeb of ScienceGoogle Scholar

  • [20]

    S. J. Kim, et al., “Real-time detection of protein-water dynamics upon protein folding by terahertz absorption spectroscopy,” Angew. Chem. Int. Ed. Engl., vol. 47, no. 34, pp. 6486–6489, 2008.CrossrefGoogle Scholar

  • [21]

     L. Baldassarre, et al., “Midinfrared plasmon-enhanced spectroscopy with germanium antennas on silicon substrates,” Nano Lett., vol. 15, no. 11, pp. 7225–7231, 2015.CrossrefWeb of ScienceGoogle Scholar

  • [22]

    A. Berrier, et al., “Ultrafast active control of localized surface plasmon resonances in silicon bowtie antennas,” Opt. Express, vol. 18, no. 22, pp. 23226, 2010.Web of ScienceCrossrefGoogle Scholar

  • [23]

    V. Conti Nibali and M. Havenith, “New insights into the role of water in biological function: Studying solvated biomolecules using terahertz absorption spectroscopy in conjunction with molecular dynamics simulations,” J. Am. Chem. Soc., vol. 136, no. 37, pp. 12800–12807, 2014.CrossrefWeb of ScienceGoogle Scholar

  • [24]

     G. V. Los, et al., “HaloTag: A novel protein labeling technology for cell imaging and protein analysis,” ACS Chem. Biol., vol. 3, no. 6, pp. 373–382, 2008.CrossrefGoogle Scholar

  • [25]

    J. Lloyd-Hughes and T.-I. Jeon, “A review of the terahertz conductivity ofbulk and nano–Materials,” J. Infrared, Millimetre Terahertz Waves, vol. 4, pp. 1–54, 2012.Google Scholar

  • [26]

    J. Frigerio, et al., “Tunability of the dielectric function of heavily doped germanium thin films for mid-infrared plasmonics,” Phys. Rev. B, vol. 94, no. 8, pp. 085202, 2016.CrossrefWeb of ScienceGoogle Scholar

  • [27]

    H. Liebe, A. Hufford, and T. Manabe, “A model for the complex permittivity of water at frequencies below 1 THz,” Int. J. Infrared Millimeter Waves, vol. 12, pp. 659–675, 1991.CrossrefGoogle Scholar

  • [28]

    P. Glancy, “Concentration-dependent effects on fully hydrated DNA at terahertz frequencies,” J Biol Phys, vol. 41, no. 3, pp. 247–256, 2015.CrossrefWeb of ScienceGoogle Scholar

  • [29]

    D. Wang, et al., “Surface chemistry and electrical properties of germanium nanowires,” J. Am. Chem. Soc., vol. 126, no. 37, pp. 11602–11611, 2004.CrossrefGoogle Scholar

  • [30]

    J. Schartner, et al., “Immobilization of proteins in their physiological active state at functionalized thiol monolayers on ATR-germanium crystals,” Chem. Bio. Chem., vol. 15, no. 17, pp. 2529–2534, 2014.CrossrefGoogle Scholar

  • [31]

    Q. Cai, et al., “1-Dodecanethiol based highly stable self-assembled monolayers for germanium passivation,” Appl. Surf. Sci., vol. 353, pp. 890–901, 2015.CrossrefWeb of ScienceGoogle Scholar

  • [32]

    J. S. Kachian, et al., “Disulfide passivation of the Ge(100)-2×1 surface,” Langmuir, vol. 27, no. 1, pp. 179–186, 2011.Web of ScienceCrossrefGoogle Scholar

  • [33]

     G. Collins, et al., “Germanium oxide removal by citric acid and thiol passivation from citric acid-terminated Ge(100),” Langmuir, vol. 30, no. 47, pp. 14123–14127, 2014.Web of ScienceCrossrefGoogle Scholar

  • [34]

    W. M. Klesse, et al., “Preparation of the Ge(001) surface towards fabrication of atomic-scale germanium devices,” Nanotechnology, vol. 22, no. 14, pp. 154604, 2011.Web of ScienceGoogle Scholar

  • [35]

    S. Löchte, et al., “Live cell micropatterning reveals the dynamics of signaling complexes at the plasma membrane,” J. Cell Biol., vol. 207, no. 3, pp. 407–418, 2014.CrossrefWeb of ScienceGoogle Scholar

  • [36]

    T. Wedeking, et al., “Spatiotemporally controlled reorganization of signaling complexes in the plasma membrane of living cells,” Small, vol. 11, no. 44, pp. 5912–5918, 2015.CrossrefWeb of ScienceGoogle Scholar

  • [37]

    T. Wedeking, et al., “Single cell GFP-trap reveals stoichiometry and dynamics of cytosolic protein complexes,” Nano Lett., vol. 15, no. 5, pp. 3610–3615, 2015.CrossrefWeb of ScienceGoogle Scholar

  • [38]

    C. You and J. Piehler, “Multivalent chelators for spatially and temporally controlled protein functionalization,” Anal. Bioanal. Chem., vol. 406, no. 14, pp. 3345–3357, 2014.Web of ScienceCrossrefGoogle Scholar

  • [39]

    J. Piehler, et al., “Protein interactions in covalently attached dextran layers,” Colloids and Surfaces B-Biointerfaces, vol. 13, no. 6, pp. 325–336, 1999.CrossrefGoogle Scholar

  • [40]

    S. Lofas and B. Johnsson, “A novel hydrogel matrix on gold surfaces in surface-plasmon resonance sensors for fast and efficient covalent immobilization of ligands,” J. Chem. Society-Chemical Commun., vol. 0, no. 21, pp. 1526–1528, 1990.Google Scholar

  • [41]

    A. Larsson, et al., “Photografted poly(ethylene glycol) matrix for affinity interaction studies,” Biomacromolecules, vol. 8, no. 1, pp. 287–295, 2007.Web of ScienceCrossrefGoogle Scholar

  • [42]

    J. Schartner, et al., “Chemical functionalization of germanium with dextran brushes for immobilization of proteins revealed by attenuated total reflection fourier transform infrared difference spectroscopy,” Anal. Chem., vol. 87, no. 14, pp. 7467–7475, 2015.Web of ScienceCrossrefGoogle Scholar

  • [43]

     F. Roemer, et al., “Investigation of the purcell effect in photonic crystal cavities with a 3D finite element maxwell solver,” Opt. Quantum Electron., vol. 39, no. 4, pp. 341–352, 2007.CrossrefWeb of ScienceGoogle Scholar

  • [44]

    D. Lisse, et al., “Selective targeting of fluorescent nanoparticles to proteins inside live cells,” Angew. Chem. Int. Ed. Engl., vol. 50, no. 40, pp. 9352–9355, 2011.CrossrefGoogle Scholar

About the article

Received: 2018-01-05

Published Online: 2018-03-07

Published in Print: 2018-03-26

Funder Name: Deutsche Forschungsgemeinschaft, Funder Id: 10.13039/501100001659, Grant Number: ESSENCE Program

Citation Information: Frequenz, Volume 72, Issue 3-4, Pages 113–122, ISSN (Online) 2191-6349, ISSN (Print) 0016-1136, DOI: https://doi.org/10.1515/freq-2018-0009.

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