Accessible Unlicensed Requires Authentication Published by De Gruyter March 7, 2018

Germanium Plasmon Enhanced Resonators for Label-Free Terahertz Protein Sensing

Maximilian Bettenhausen, Friedhard Römer, Bernd Witzigmann, Julia Flesch, Rainer Kurre, Sergej Korneev, Jacob Piehler, Changjiang You, Marcin Kazmierczak, Subhajit Guha, Giovanni Capellini and Thomas Schröder
From the journal Frequenz

Abstract

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.

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

Acknowledgements

The work presented has been funded in part by the German Research Foundation (DFG) within the project ESSENCE (Electromagnetic Sensors for the Life Sciences).

References

[1] H.-J. Wu, et al., “Membrane-protein binding measured with solution-phase plasmonic nanocube sensors,” Nat. Methods, vol. 9, pp. 1189, 2012.10.1038/nmeth.2211 Search in Google 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, 2013.10.1021/ac401673e Search in Google 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, 2013.10.1002/adma.201205214 Search in Google Scholar

[4] P. Chen, et al., “Multiplex serum cytokine immunoassay using nanoplasmonic biosensor microarrays,” ACS Nano, vol. 9, no. 4, pp. 4173–4181, 2015.10.1021/acsnano.5b00396 Search in Google Scholar

[5] Y. Song, et al., “AC electroosmosis-enhanced nanoplasmofluidic detection of ultralow-concentration cytokine,” Nano Lett., vol. 17, no. 4, pp. 2374–2380, 2017.10.1021/acs.nanolett.6b05313 Search in Google 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, 2006.10.1021/ac060024+ Search in Google 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, 2010.10.1016/j.bios.2010.08.063 Search in Google Scholar

[8] X. Yu, D. Xu, and Q. Cheng, “Label-free detection methods for protein microarrays,” Proteomics, vol. 6, no. 20, pp. 5493–5503, 2006.10.1002/pmic.200600216 Search in Google 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, 2012.10.1016/j.bios.2012.02.038 Search in Google Scholar

[10]  G. Gauglitz, “Multiple reflectance interference spectroscopy measurements made in parallel for binding studies,” Rev. Sci. Instruments, vol. 76, no. 6, pp. 062224, 2005.10.1063/1.1906164 Search in Google 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, 2009.10.1073/pnas.0907459106 Search in Google 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, 2008.10.1073/pnas.0802289105 Search in Google 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, 2013.10.1016/j.bbamem.2013.04.026 Search in Google Scholar

[14] D. Rodrigo, et al., “Mid-infrared plasmonic biosensing with graphene,” Science, vol. 349, no. 6244, pp. 165–168, 2015.10.1126/science.aab2051 Search in Google Scholar

[15] R. Balu, et al., “Terahertz spectroscopy of bacteriorhodopsin and rhodopsin: similarities and differences,” Biophys. J., vol. 94, no. 8, pp. 3217–3226, 2008.10.1529/biophysj.107.105163 Search in Google 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, 2003.10.1016/S0006-3495(03)74562-7 Search in Google 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, 2007.10.1073/pnas.0709207104 Search in Google 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, 2008.10.2976/1.2976661 Search in Google 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, 2008.10.1021/ja0746520 Search in Google 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, 2008.10.1002/anie.200802281 Search in Google 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, 2015.10.1021/acs.nanolett.5b03247 Search in Google 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, 2010.10.1364/OE.18.023226 Search in Google 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, 2014.10.1021/ja504441h Search in Google 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, 2008.10.1021/cb800025k Search in Google 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. Search in 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, 2016.10.1103/PhysRevB.94.085202 Search in Google 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, 1991.10.1007/BF01008897 Search in Google Scholar

[28] P. Glancy, “Concentration-dependent effects on fully hydrated DNA at terahertz frequencies,” J Biol Phys, vol. 41, no. 3, pp. 247–256, 2015.10.1007/s10867-015-9377-0 Search in Google 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, 2004.10.1021/ja047435x Search in Google 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, 2014.10.1002/cbic.201402478 Search in Google 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, 2015.10.1016/j.apsusc.2015.06.174 Search in Google Scholar

[32] J. S. Kachian, et al., “Disulfide passivation of the Ge(100)-2×1 surface,” Langmuir, vol. 27, no. 1, pp. 179–186, 2011.10.1021/la103614f Search in Google 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, 2014.10.1021/la503819z Search in Google 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. Search in Google 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, 2014.10.1083/jcb.201406032 Search in Google 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, 2015.10.1002/smll.201502132 Search in Google 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, 2015.10.1021/acs.nanolett.5b01153 Search in Google 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, 2014.10.1007/s00216-014-7803-y Search in Google 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, 1999.10.1016/S0927-7765(99)00046-6 Search in Google 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. Search in Google Scholar

[41] A. Larsson, et al., “Photografted poly(ethylene glycol) matrix for affinity interaction studies,” Biomacromolecules, vol. 8, no. 1, pp. 287–295, 2007.10.1021/bm060685g Search in Google 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, 2015.10.1021/acs.analchem.5b01823 Search in Google 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, 2007.10.1007/s11082-007-9089-1 Search in Google 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, 2011.10.1002/anie.201101499 Search in Google Scholar

Supplemental Material

The online version of this article offers supplementary material (https://doi.org/10.1515/freq-2018-0009).

Received: 2018-1-5
Published Online: 2018-3-7
Published in Print: 2018-3-26

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