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4 - Microwave Biosensors for Noninvasive Molecular and Cellular Investigations

By
Katia Grenier  and
David Dubuc
Edited by
Isar Mostafanezhad ,
Olga Boric-Lubecke  and
Jenshan Lin
Katia Grenier
Affiliation:
LAAS-CNRS, France
David Dubuc
Affiliation:
LAAS-CNRS, France
Isar Mostafanezhad
Affiliation:
University of Hawaii, Manoa
Olga Boric-Lubecke
Affiliation:
University of Hawaii, Manoa
Jenshan Lin
Affiliation:
University of Florida
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Summary

This chapter will give a status on the current possibilities of analysis at the molecular and cellular levels enabled by the convergence of microwave dielectric spectroscopy and the use of microtechnologies. Highlights of the technique will be addressed, such as its noninvasivity, its specificity in terms of high-frequency signature, its compatibility with high ionic and nutrient contents classically encountered with cell culture media, and its suitability and sufficient sensitivity for cell probing, even down to single-cell investigations. These particularities notably will be performed in the context of cancer studies in order to offer complementary noninvasive analyzing tools to the biologists and physicians for living cells in their typical liquid microenvironment.

Introduction

There are plenty of physical ways to identify and characterize (bio-)matter physically and/or chemically. Whereas humans exploit their traditional senses (sight, hearing, taste, smell, and touch) to probe the environment, (artificial) sensors – especially biosensors, which are the topic of this chapter – also rely on such sensing mechanisms, for example, mechanical (touch) and optical (sight), but also on other types of interactions, for example, electromagnetic. Such techniques feature a key characteristic: the frequency of the electromagnetic waves can be varied over a range (narrow or broad) to get a rich set of data from spectra, and consequently, the technique is called spectroscopy. Combined with the massive progress in micro- and nanotechnology, miniature biosensors based on dielectric spectroscopy have been in use for several decades, first initiated in direct current (dc) and low frequencies (kilohertz and megahertz) and now reaching microwave and millimeter-wave ranges.

This chapter aims at showing the status of the current possibilities of analysis at the molecular and cellular levels enabled by the convergence of microwave dielectric spectroscopy and the use of microtechnologies. To understand the interests of developing microwave-based and miniature biosensors for molecular and cellular investigations, examples of the main and current cellular analyzing techniques that are available in biolabs will be given, followed by an introduction to microwave dielectric spectroscopy. Highlights of such a technique will then be addressed in terms of noninvasivity, specificity, compatibility with the high ionic and nutrient contents classically encountered in cell culture media, and suitability and sufficient sensitivity for cell probing, even down to single-cell investigations.

Type
Chapter
Information
Medical and Biological Microwave Sensors and Systems
, pp. 124 - 153
Publisher: Cambridge University Press
Print publication year: 2017

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References

[1] Carey, J. L., McCoy, J. P., and Keren, D. F., Flow Cytometry in Clinical Diagnosis, (Chicago: American Society for Clinical Pathology Press, 2007).Google Scholar
[2] Parry, B. R. et al., “The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity,” Cell 156 (2014): 183–94.CrossRefGoogle ScholarPubMed
[3] Carlo, D. Di and Lee, L. P., “Dynamic single-cell analysis for quantitative biology,” Anal. Chem., 78 (2006): 7918–25.CrossRefGoogle ScholarPubMed
[4] Fricke, H., “A mathematical treatment of the electric conductivity and capacity of disperse systems. I. The electric conductivity of a suspension of homogeneous spheroids,” Phys. Rev., 24 (1924): 575–87.CrossRefGoogle Scholar
[5] Cole, K. S., “Electric phase angle of cell membranes,” J. Gen. Physiol., 15 (1932): 641–49.CrossRefGoogle ScholarPubMed
[6] Polk, C. and Postow, E., Handbook of Biological Effects of Electromagnetic Fields (Boca Raton, FL: CRC Press, 1996), chap. 1.Google Scholar
[7] Coulter, W. H., “High speed automatic blood cell counter and cell analyzer,” Proc. Natl. Electron. Conf., 12 (1956): 1034–40.Google Scholar
[8] Hoffman, R. A. and Britt, W. B., “Flow-system measurement of cell impedance properties,” J. Histochem. Cytochem., 27 (1979): 234–40.CrossRefGoogle ScholarPubMed
[9] Sun, T. and Morgan, H., “Single-cell microfluidic impedance cytometry: a review,” Microfluid. Nanofluid., 8 (2010): 423–43.CrossRefGoogle Scholar
[10] Holmes, D. et al., “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip, 9 (2009): 2881–9.CrossRefGoogle ScholarPubMed
[11] Colella, L. et al., “Microelectrode-based dielectric spectroscopy of glucose effect on erythrocytes,” Bioelectrochemistry, 85 (2012): 14–20.CrossRefGoogle ScholarPubMed
[12] Baker, Matthew J. et al. “Using Fourier transform IR spectroscopy to analyze biological materials,” Nature Protocols, 9 (2014): 1771–91.CrossRefGoogle ScholarPubMed
[13] Townes, C. H. and Schawlow, A. L., Microwave Spectroscopy (Mineola, NY: Dover, 2012).Google Scholar
[14] Patterson, D., Schnell, M., and Doyle, J. M., “Enantiomer-specific detection of chiral molecules via microwave spectroscopy,” Nature, 497 (2013): 475–8.CrossRefGoogle ScholarPubMed
[15] Kupfer, K., Electromagnetic Aquametry (Berlin: Springer, 2004).Google Scholar
[16] Izgorodina, E. I., Forsyth, M., and MacFarlane, D. R., “On the components of the dielectric constants of ionic liquids: ionic polarization?,” Phys. Chem. Chem. Phys., 11(14) (2009): 2452–8.CrossRefGoogle ScholarPubMed
[17] Shaker, M. et. al., “An impedance-based flow microcytometer for single cell morphology discrimination,” Lab Chip, 14 (2014): 2548–55.CrossRefGoogle ScholarPubMed
[18] Debye, P., Polar Molecules (New York: Chemical Catalog Co., 1929).Google Scholar
[19] Kaatze, U., “Complex permittivity of water as a function of frequency and temperature,” J. Chem. Eng. Data, 34 (1989): 371-4.CrossRefGoogle Scholar
[20] National Physical Laboratory, A Guide to Characterization of Dielectric Materials at RF and Microwave Frequencies (Londres: NPL, 2003).
[21] Marsland, T. P. and Evans, S., “Dielectric measurements with an open-ended coaxial probe,” IEEE Proc. 134(4) (1987): 341–9.Google Scholar
[22] Zajicek, R., Smejkal, T., Oppl, L., and Vrba, J., “Waveguide probes for complex permittivity measurement,” presented at the 14th Conference on Microwave Techniques, Prague, 2008.
[23] Toropainen, A., Vainikainen, P., and Drossos, A., “Method for accurate measurement of complex permittivity of tissue equivalent liquids,” Electron. Lett. 36(1) (2000): 32–4.CrossRefGoogle Scholar
[24] Esteban, H., Catal-Civera, J. M., Cogollos, S., and Boria, V. E., “Characterization of complex permittivity properties of materials in rectangular waveguides using a hybrid iterative method,” IEEE Microwave Guided Wave Lett., 10(5) (2000): 186–8.CrossRefGoogle Scholar
[25] Stuchly, S. S. and Bassey, C. E., “Microwave coplanar sensors for dielectric measurements,” Measure. Sci. Technol., 9 (1998): 1324–9.CrossRefGoogle Scholar
[26] Roelvink, J., Trabelsi, S., and Nelson, S. O., “A planar transmission-line sensor for measuring the microwave permittivity of liquid and semisolid biological materials,” IEEE Trans. Instrum. Measure., 62(11) (2013): 2974–82.CrossRefGoogle Scholar
[27] 85070E Dielectric Probe Kit; available at: www.home.agilent.com.
[28] Booth, James C., Orloff, Nathan D., Mateu, Jordi, Janezic, Michael, Rinehart, Matthew et al., “Quantitative permittivity measurements of nanoliter liquid volumes in microfluidic channels to 40 GHz,” IEEE Trans. Instrum. Measure., 59(12) (2010): 3279.CrossRefGoogle Scholar
[29] Grenier, K., Dubuc, D., Poleni, P. E., Kumemura, M., Toshiyoshi, H., et al., “Integrated broadband microwave and microfluidic sensor dedicated to bioengineering,” IEEE Trans. Microwave Theory Techn., 57(12) (2009): 3246–53.CrossRefGoogle Scholar
[30] [Facer, G. R., Notterman, D. A., and Sohn, L. L., “Dielectric spectroscopy for bioanalysis: from 40 Hz to 26.5 GHz in a microfabricated wave guide,” Appl. Phys. Lett., 78(7) (2001): 906–8.CrossRefGoogle Scholar
[31] Laurette, S., Treizebre, A., Affouard, F., and Bocquet, B., “Subterahertz characterization of ethanol hydration layers by microfluidic system,” Appl. Phys. Lett., 97(11) (2010).CrossRefGoogle Scholar
[32] Artis, F., Dubuc, D., Fournié, J.-J., Poupot, M., and Grenier, K., “Sub-microliter microwave dielectric spectroscopy for identification and quantification of carbohydrates in aqueous solution,” IEEE Biowireless Proc., 2015.
[33] Hofmann, M., Fischer, G., Weigel, R., and Kissinger, D., “Microwave-based noninvasive concentration measurements for biomedical applications,” IEEE Trans. MTT, 61(5) (2013): 2195–204.CrossRefGoogle Scholar
[34] Fuchs, K. and Kaatze, U., “Molecular dynamics of carbohydrate aqueous solutions: dielectric relaxation as a function of glucose and fructose concentration,” J. Phys. Chem. B, 105 (2001): 2036–42.CrossRefGoogle Scholar
[35] Basey-Fisher, T. H., Hanham, S. M., Andresen, H., Maier, S. A., Stevens, M. M. et al., “Microwave Debye relaxation analysis of dissolved proteins: towards free-solution biosensing,” Appl. Phys. Lett., 99 (2011): 233703.CrossRefGoogle Scholar
[36] Gregory, A. P. and Clarke, R. N., “A review of RF and microwave techniques for dielectric measurements on polar liquids,” IEEE Trans. Dielect. Elect. Insulation, 13(4) (2006): 727–43.CrossRefGoogle Scholar
[37] Kim, J., Babajanyan, A., Hovsepyan, A., Lee, K., and Friedman, B., “Microwave dielectric resonator biosensor for aqueous glucose solution,” Rev. Sci. Instrum., 79 (2008).CrossRefGoogle ScholarPubMed
[38] Neshat, M., Gigoyan, S., Saeedkia, D., and Safavi-Naeini, S., “Traveling-wave whispering gallery resonance sensor in millimeter-wave range,” Electron. Lett., 44(17) (2008): 1020–2.CrossRefGoogle Scholar
[39] Kawabata, H. and Kobayashi, Y., “Accurate measurements of complex permittivity of liquid based on a TM010 mode cylindrical cavity method,” presented at the European Microwave Conference, Paris, 2005.
[40] Kapilevich, B. and Litvak, B., “Optimized microwave sensor for online concentration measurements of binary liquid mixtures,” IEEE Sens. J., 11(10) (2011): 2611–16.CrossRefGoogle Scholar
[41] Yu, Kapilevich B., Ogourtsov, S. G., Belenky, V. G., Maslenikov, A. B., and Omar, A. S., “Accurate microwave resonant method for complex permittivity measurements of liquids,” IEEE Trans. Microwave Theory Tech., 48(11) (2000): 2159–64.Google Scholar
[42] Lee, H. J., Lee, H. S., Yoo, K. H., and Yook, J. G., “DNA sensing using split-ring resonator alone at microwave regime,” J. Appl. Phys., 108 (2010).Google Scholar
[43] Kim, Y. H., Jang, K., Yoon, Y. J., and Kim, Y. J., “A novel relative humidity sensor based on microwave resonators and a customized polymeric film,” Sensors Actuators B, 117 (2005): 315–22.Google Scholar
[44] Liu, C. and Pu, Y., “A microstrip resonator with slotted ground plane for complex permittivity measurements of liquids”, IEEE Microwave Wireless Components Lett., 18(4) (2008): 257–9.Google Scholar
[45] Chretiennot, Thomas, Dubuc, David, and Grenier, Katia, “Bi-frequency-based microwave liquid sensor for multiple solutes quantification in aqueous solution,” in Proceedings of the 2014 44th European Microwave Conference (IEEE-EuMW) (Piscataway, NJ: IEEE, 2014), pp. 287–90.Google Scholar
[46] Li, L. and Uttamchandani, D., “A microwave dielectric biosensor based on suspended distributed MEMS transmission lines,” IEEE Sensors J., 9(12) (2009): 1825–30.CrossRefGoogle Scholar
[47] Leea, H.-J. et. al., “A planar split-ring resonator-based microwave biosensor for label-free detection of biomolecules,” Sensors Actuators B, 169 (2012): 26–31.Google Scholar
[48] Mateu, J., Orloff, N., Rinehart, M., and Booth, J. C., “Broadband permittivity of liquids extracted from transmission line measurements of microfluidic channels,” 2007 IEEE/MIT-S International Microwave Symposium (IEEE T-MTT-S) (Piscatawat, NJ: IEEE, 2007), pp. 523–6.Google Scholar
[49] Anghyun, S., Stintzing, T., Block, I., Pavlidis, D., Rieke, M. et al. “High frequency wideband permittivity measurements of biological substances using coplanar waveguides and application to cell suspensions,” 2008 IEEE/MIT-S International Microwave Symposium (Piscataway, NJ: IEEE, 2008), pp. 915–18.Google Scholar
[50] Ferrier, G. A., Romanuik, S. F., Thomson, D. J., Bridges, G. E., and Freeman, M. R., “A microwave interferometric system for simultaneous actuation and detection of single biological cells,” Lab Chip, 9(2009): 3406–12.CrossRefGoogle ScholarPubMed
[51] Denef, N., Moreno-Hagelsieb, L., Laurent, G., Pampina, R., Foultierb, B., et al. “RF detection of DNA based on CMOS inductive and capacitive sensors,” in 34th European Microwave Conference (EuMW) (2004).
[52] Dalmay, C., Pothier, A., Blondy, P., Lalloue, F., and Jauberteau, M.-O., “Label free biosensors for human cell characterization using radio and microwave frequencies,” in 2008 IEEE/MIT-S International Microwave Symposium (Piscataway, NJ: IEEE, 2008).Google Scholar
[53] Artis, F., Blatche, C., Dubuc, D., and Grenier, K., “Biological cells proliferation in microwave microsystems,” in 2008 IEEE/MIT-S International Microwave Symposium (Piscataway, NJ: IEEE, 2008) 2012.Google Scholar
[54] Onaral, B., Sun, H. H., and Schwan, H. P., “Electrical properties of bioelectrodes,” IEEE Trans. on Biomed.l Eng., BME-31(12) (1984): 827–32.Google ScholarPubMed
[55] Artis, F., Dubuc, D., Fournié, J.-J., Poupot, M., and Grenier, K., “Microwave dielectric bio-sensing for precise and repetitive living cells suspension analysis,” IEEE European Microwave Conference Proceedings, Nuremberg, Germany, 2013, pp. 468–70.
[56] Artis, F., Dubuc, D., Fournié, J.-J., Poupot, M., and Grenier, K., “ Microwave dielectric spectroscopy for biological cells suspensions analysis and proliferation evaluation,” IEEE European Microwave Conference Proceedings, Rome, Italy, October 2014.Google Scholar
[57] Chen, T., Dubuc, D., and Grenier, K., “Accurate nanoliter liquid characterization for biomedical applications: toward non-invasive living cells monitoring,” IEEE Trans. Microwave Theory Techn., 60(12) (2012): 4171–7.CrossRefGoogle Scholar
[58] Chen, T., Dubuc, D., Poupot, M., Fournié, J.-J., and Grenier, K., “Microwave biosensor dedicated to the dielectric spectroscopy of a single alive biological cell in its culture medium,” IEEE International Microwave Symposium, Seattle, WA, June 2013.Google Scholar
[59] Nikolic-Jaric, M., Romanuik, S. F., Ferrier, G. A., Butler, M., Sunley, K., Thomson, D.J., Freeman, M.R., “Microwave frequency sensor for detection of biological cells in microfluidic channels,” Biomicrofluidics, 3 (2009): 034103.CrossRefGoogle ScholarPubMed
[60] Yang, Y. et al., “Distinguishing the viability of a single yeast cell with an ultra-sensitive radio frequency sensor,” Lab on a Chip, 10 (2010): 553–5.CrossRefGoogle ScholarPubMed
[61] Gabriel, C., Gabriel, S., and Corthout, E, “The dielectric properties of biological tissues. I. Literature survey,” Phys. Med. Biol., 41 (1996): 2231–49.CrossRefGoogle ScholarPubMed
[62] Gabriel, S., Lau, R. W., and Gabriel, C., “The dielectric properties of biological tissues. III. Parametric models for the dielectric spectrum of tissues.” Phys. Med. Biol., 41 (1996): 2271–93.CrossRefGoogle ScholarPubMed
[63] Tofighi, M. R. and Dayroush, A. S., “Study of the activity of neurological cell solutions using complex permittivity measurement,” 2008 IEEE/MIT-S International Microwave Symposium (Piscataway, NJ: IEEE, 2002), pp. 1763–6.Google Scholar
[64] O'Rourke, A. P. et al., “Dielectric properties of human normal, malignant and cirrhotic liver tissue: in vivo and ex vivo measurements from 0.5 to 20 GHz using a precision opten-ended coaxial probe,” Phys. Med. Biol., 52 (2007): 4707–19.Google ScholarPubMed
[65] Fear, E. C., Meaney, P. M., and Stuchly, M. A., “Microwaves for breast cancer detection?,” IEEE Potentials, Feb–March (2003): 12–18.
[66] Lazebnik, M. et al., “A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries,” Phys. Med. Biol., 2 (2007): 6093–115.Google Scholar
[67] Artis, F., Dubuc, D., Fournié, J.-J., Poupot, M., and Grenier, K., “Microwave dielectric spectroscopy of cell membrane permeabilization with saponin on human B lymphoma cells,” 2008 IEEE/MIT-S International Microwave Symposium (Piscataway, NJ: IEEE, 2014).Google Scholar
[68] Grenier, K., Dubuc, D., Chen, T., Artis, F., Chrétiennot, T., et al., “Recent advances in microwave-based dielectric spectroscopy at the cellular level for cancer investigations,” IEEE Trans. Microwave Theory Techn., 61(5) (2013): 2023–30.CrossRefGoogle Scholar
[69] Sha, L., Ward, E. R., and Stroy, B., “A review of dielectric properties of normal and malignant breast tissue,” Proc. IEEE Southeast Con, 2002.
[70] Töpfer, F., Dudorov, S., and Oberhammer, J., “Two-dimensional near-field millimeter-wave scanning with micromachined probe for skin cancer diagnosis,” 2013 IEEE 26th International Conference on Micro Electro Mechanical Systems (MEMS) (Piscataway, NJ: IEEE, 2013), pp. 1057–60.Google Scholar
[71] Töpfer, F., Emtestam, L., and Oberhammer, J., “Dermatological verification of micromachined millimeter-wave skin-cancer probe,” in 2014 IEEE MTT-S International Microwave Symposium (IMS2014) (Piscataway, NJ: IEEE, 2014).Google Scholar

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