Biological Detection with Terahertz Spectroscopy

  • Tatiana GlobusEmail author
  • Boris Gelmont
Part of the Integrated Analytical Systems book series (ANASYS)


This chapter describes the basic principles of resolved vibrational spectroscopy of biological macromolecules and species in the sub-terahertz spectral range of radiation and the application of this technology for the biological detection including material in air. The origin of THz spectroscopic signatures specific to bioparticles is based upon low energy internal molecular vibrations that absorb radiation at characteristic frequencies. The multiple resonance features provide distinctive spectral fingerprints for detection and identification of harmful biological species. The sensitivity and selectivity of THz biosensing is demonstrated. The possibility to make THz detector systems for the biological detection is discussed.


Biological Macromolecule Sample Preparation Technique Spectroscopic Signature Absorption Absorption Fourier Transform Spectroscopy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work is supported by contracts from the ARO #W911NF-08-C-0049 & #W911NF-10-C-0076 and by the Defense Threat Reduction Agency, grant #HDTRA1-08-1-0038.


  1. 1.
    Van Zandt LL, Saxena SK (1992) Identifying and Interpreting Spectral Feaures of DNA in the Microwave-Submillimeter Frequency Range. In: Sarma RH, Sarma MH (eds) Structure and Function, vol 1: Nuceleic Acids. Adenine Press, Schenectady, N.Y., pp 237–243, and references thereinGoogle Scholar
  2. 2.
    Duong TH, Zakrzewska K (1997) Calculation and analysis of low frequency normal modes for DNA. J Comput Chem 18 (6):796–811. doi:10.1002/(SICI)1096-987X(19970430)18:6<796::AID-JCC5>3.0.CO;2–NGoogle Scholar
  3. 3.
    Smye S, Chamberlain J, Fitzgerald A, Berry E (2001). The interaction between terahertz radiation and biological tissue. J. Phys. Med. Biol. 46: R101–112CrossRefGoogle Scholar
  4. 4.
    Mie scattering. Accessed 20 Januari 2014. Reyleigh scattering Accessed 20 Januari 2014
  5. 5.
    Globus T, Bykhovskaia M, Woolard D, Gelmont B (2003) Sub-millimetre wave absorption spectra of artificial RNA molecules. J Phys D: Appl Phys 36 (11):1314–1322. doi:10.1088/0022-3727/36/11/312Google Scholar
  6. 6.
    Globus T, Khromova T, Woolard D, Gelmont B (2004) Terahertz Fourier transform characterization of biological materials in solid and liquid phases. Proc SPIE 5268:10–18. doi:10.1117/12.519172Google Scholar
  7. 7.
    Korter TM, Plusquellic DF (2004) Continuous-wave terahertz spectroscopy of biotin: vibrational anharmonicity in the far-infrared. Chem Phys Lett 385 (1–2):45–51. doi:10.1016/j.cplett.2003.12.060CrossRefGoogle Scholar
  8. 8.
    De Lucia FC THz spectroscopy – techniques and applications. In: IEEE Microwave Theory and Techniques Society International Microwave Symposium Digest, vol 3, Seattle, WA, USA, 2–7 June 2002. pp 1579–1582. doi:10.1109/MWSYM.2002.1012158Google Scholar
  9. 9.
    Payne JM (1989) Millimeter and submillimeter wavelength radioastronomy. Proc IEEE 77 (7):993–1017. doi:10.1109/5.30751CrossRefGoogle Scholar
  10. 10.
    Phillips TG, Keene J (1992) Submillimeter astronomy [heterodyne spectroscopy]. Proc IEEE 80 (11):1662–1678. doi:10.1109/5.175248CrossRefGoogle Scholar
  11. 11.
    Waters JW, Froidevaux L, Read WG, Manney GL, Elson LS, Flower DA, Jarnot RF, Harwood RS (1993) Stratospheric CIO and ozone from the Microwave Limb Sounder on the Upper Atmosphere Research Satellite. Nature 362 (6421):597–602. doi:10.1038/362597a0CrossRefGoogle Scholar
  12. 12.
    Woolard DL, Brown ER, Pepper M, Kemp M (2005) Terahertz Frequency Sensing and Imaging: A Time of Reckoning Future Applications? Proc IEEE 93 (10):1722–1743. doi:10.1109/JPROC.2005.853539CrossRefGoogle Scholar
  13. 13.
    Heilweil EJ, Plusquellic DF (2007) Terahertz Spectroscopy of Biomolecules. In: Dexheimer SL (ed) Terahertz Spectrocopy: Principles and Applications. Optical Science and Engineering. CRC Press, Boca Raton, pp 269–297Google Scholar
  14. 14.
    Johnson TJ, Valentine NB, Sharpe SW (2005) Mid-infrared versus far-infrared (THz) relative intensities of room-temperature Bacillus spores. Chem Phys Lett 403 (1–3):152–157. doi:10.1016/j.cplett.2004.12.095CrossRefGoogle Scholar
  15. 15.
    Globus T, Woolard D, Bykhovskaia M, Gelmont B, Werbos L, Samuels A (2003) THz Spectroscopic Sensing of DNA and Related Biological Materials. Int J High Speed Electron Syst 13 (04):903–936. doi:10.1142/S0129156403002083CrossRefGoogle Scholar
  16. 16.
    Bykhovskaia M, Gelmont B, Globus T, Woolard DL, Samuels AC, Duong TH, Zakrzewska K (2001) Prediction of DNA far-IR absorption spectra based on normal mode analysis. Theor Chem Acc 106 (1–2):22–27. doi:10.1007/s002140100259CrossRefGoogle Scholar
  17. 17.
    Globus T, Bykhovskaia M, Gelmont B, Woolard DL (2002) Far-infrared phonon modes of selected RNA molecules. Proc SPIE 4574:119–128. doi:10.1117/12.455149Google Scholar
  18. 18.
    Li X, Globus T, Gelmont B, Salay LC, Bykhovski A (2008) Terahertz Absorption of DNA Decamer Duplex. J Phys Chem A 112 (47):12090–12096. doi:10.1021/jp806630wCrossRefGoogle Scholar
  19. 19.
    Bykhovski A, Li X, Globus T, Khromova T, Gelmont B, Woolard D, Samuels AC, Jensen JO (2005) THz absorption signature detection of genetic material of E. coli and B. subtilis. Proc SPIE 5995:59950N.1–10. doi:10.1117/12.629959Google Scholar
  20. 20.
    Bykhovski A, Globus T, Khromova T, Gelmont B, Woolard D, Bykhovskaia M (2006) An analysis of the THz frequency signatures in the cellular components of biological agents. Proc SPIE 6212:62120H.1–10. doi:10.1117/12.665272 and Bykhovski A, Globus T, Khromova T, Gelmont B, Woolard D (2007) Analysis of the THz Frequency Signatures in the Cellular Components of Biological Agents. Int J High Speed Electron Syst 17 (02):225–237. doi:10.1142/S012915640700445XCrossRefGoogle Scholar
  21. 21.
    Bykhovski A, Globus T, Khromova T, Gelmont B, Woolard D (2008) Resonant Terahertz Spectroscopy of Bacterial Thioredoxin in Water: Simulation and Experiment. In: Woolard D, Jensen J (eds) Spectral Sensing Research For Water Monitoring Applications And Frontier Science And Technology For Chemical, Biological And Radiological Defense. Selected Topics in Electronics and Systems, vol 48. World Scientific, Singapore, pp 367–375. doi:10.1142/9789812833242_0033Google Scholar
  22. 22.
    Alijabbari N, Chen Y, Sizov I, Globus T, Gelmont B (2012) Molecular dynamics modeling of the sub-THz vibrational absorption of thioredoxin from E. coli. J Mol Model 18 (5):2209–2218. doi:10.1007/s00894-011-1238-6CrossRefGoogle Scholar
  23. 23.
    Globus T (2010) Low-Terahertz Resonance Spectroscopy for Fingerprinting of Biological and Organic Materials. Paper presented at the Chemical and Biological Defense Science and Technology Conference, Orlando, 15–19 November 2010Google Scholar
  24. 24.
    Globus T, Moyer AM, Gelmont B, Khromova T, Lvovska MI, Sizov I, Ferrance J (2013) Highly Resolved Sub-Terahertz Vibrational Spectroscopy of Biological Macromolecules and Cells. IEEE Sens J 13 (1):72–79. doi:10.1109/JSEN.2012.2224333CrossRefGoogle Scholar
  25. 25.
    Globus T, Moyer A, Gelmont B, Sizov I, Khromova T (2013) Dissipation Time in Molecular Dynamics and Discriminative Capability of Sub-THz Spectroscopic Characterization of Biological Molecules and Cells. Paper presented at the Chemical and Biological Defense Science and Technology Conference, Las Vegas, 14–18 November 2011Google Scholar
  26. 26.
    Crowe TW, Globus T, Woolard DL, Hesler JL (2004) Terahertz sources and detectors and their application to biological sensing. Philos Trans R Soc London, Ser A 362 (1815):365–377. doi:10.1098/rsta.2003.1327Google Scholar
  27. 27.
    Beetz CP, Ascarelli G (1982) Far-infrared absorption of nucleotides and poly(I)·poly(C) RNA. Biopolym 21 (8):1569–1586. doi:10.1002/bip.360210808CrossRefGoogle Scholar
  28. 28.
    Giordano R, Mallamace F, Micali N, Wanderlingh F, Baldini G, Doglia S (1983) Light scattering and structure in a deoxyribonucleic acid solution. Phys Rev A 28 (6):3581–3588. doi:10.1103/PhysRevA.28.358CrossRefGoogle Scholar
  29. 29.
    Lindsay SM, Powell J (1983) Light scattering studies of the lattice vibrations of DNA. In: Clementi E, Sarma RH (eds) Structure and Dynamics: Nucleic Acids and Proteins. Adenine Press, New York, pp 241–259Google Scholar
  30. 30.
    Edwards GS, Davis CC, Saffer JD, Swicord ML (1984) Resonant Microwave Absorption of Selected DNA Molecules. Phys Rev Lett 53 (13):1284–1287. doi:10.1103/PhysRevLett.53.1284CrossRefGoogle Scholar
  31. 31.
    Wittlin A, Genzel L, Kremer F, Häseler S, Poglitsch A, Rupprecht A (1986) Far-infrared spectroscopy on oriented films of dry and hydrated DNA. Phys Rev A 34 (1):493–500. doi:10.1103/PhysRevA.34.493CrossRefGoogle Scholar
  32. 32.
    Powell JW, Edwards GS, Genzel L, Kremer F, Wittlin A, Kubasek W, Peticolas W (1987) Investigation of far-infrared vibrational modes in polynucleotides. Phys Rev A 35 (9):3929–3939. doi:10.1103/PhysRevA.35.3929CrossRefGoogle Scholar
  33. 33.
    Weidlich T, Powell JW, Genzel L, Rupprecht A (1990) Counterion effects on the far-IR vibrational spectra of poly(rI) poly(rC). Biopolym 30 (3–4):477–480. doi:10.1002/bip.360300324CrossRefGoogle Scholar
  34. 34.
    Powell JW, Peticolas WL, Genzel L (1991) Observation of the far-infrared spectrum of five oligonucleotides. J Mol Struct 247 (0):107–118. doi:10.1016/0022-2860(91)87067-R.CrossRefGoogle Scholar
  35. 35.
    Gabriel C, Grant EH, Tata R, Brown PR, Gestblom B, Noreland E (1987) Microwave absorption in aqueous solutions of DNA. Nature 328 (6126):145–146. doi:10.1038/328145a0CrossRefGoogle Scholar
  36. 36.
    Ferguson B, Zhang X-C (2002) Materials for terahertz science and technology. Nat Mater 1 (1):26–33. doi:10.1038/nmat708CrossRefGoogle Scholar
  37. 37.
    Terahertz time-domain spectroscopy. Accessed 29 January 2014
  38. 38.
    Globus T, Woolard D, Crowe T, W., Khromova T, Gelmont B, Hesler J (2006) Terahertz Fourier transform characterization of biological materials in a liquid phase. J Phys D: Appl Phys 39 (15):3405–3413. doi:10.1088/0022-3727/39/15/028Google Scholar
  39. 39.
    Markelz AG, Roitberg A, Heilweil EJ (2000) Pulsed terahertz spectroscopy of DNA, bovine serum albumin and collagen between 0.1 and 2.0 THz. Chem Phys Lett 320 (1–2):42–48. doi:10.1016/S0009-2614(00)00227-XCrossRefGoogle Scholar
  40. 40.
    Walther M, Fischer B, Schall M, H, Jepsen PU (2000) Far-infrared vibrational spectra of all-trans, 9-cis and 13-cis retinal measured by THz time-domain spectroscopy. Chem Phys Lett 332 (3–4):389–395. doi:10.1016/S0009-2614(00)01271-9CrossRefGoogle Scholar
  41. 41.
    Han PY, Tani M, Usami M, Kono S, Kersting R, Zhang XC (2001) A direct comparison between terahertz time-domain spectroscopy and far-infrared Fourier transform spectroscopy. J Appl Phys 89 (4):2357–2359. doi:10.1063/1.1343522CrossRefGoogle Scholar
  42. 42.
    Brown E, Siegel P, Samuels A, Woolard L (2003) High-Resolution Transmission Measurements of Bacillus Subtilis Between 300 and 500 GHz. Paper presented at the International Symposium on Spectral Sensing Research, Santa Barbara, CA, USA, 2–6 June 2003Google Scholar
  43. 43.
    Brown ER, Bjarnason JE, Chan TLJ, Lee AWM, Celis MA (2004) Optical attenuation signatures of Bacillus subtillis in the THz region. Appl Phys Lett 84 (18):3438–3440. doi:10.1063/1.1711167CrossRefGoogle Scholar
  44. 44.
    Brown ER, Bjarnason J, Chan TLJ, Driscoll DC, Hanson M, Gossard AC (2004) Room temperature, THz photomixing sweep oscillator and its application to spectroscopic transmission through organic materials. Rev Sci Instrum 75 (12):5333–5342. doi:10.1063/1.1808912CrossRefGoogle Scholar
  45. 45.
    Verghese S, McIntosh KA, Calawa S, DiNatale WF, Duerr EK, Molvar KA (1998) Generation and detection of coherent terahertz waves using two photomixers. Appl Phys Lett 73 (26):3824–3826. doi:10.1063/1.122906CrossRefGoogle Scholar
  46. 46.
    Bjarnason JE, Brown ER (2005) Sensitivity measurement and analysis of an ErAs:GaAs coherent photomixing transceiver. Appl Phys Lett 87 (13):134105.1–3. doi:10.1063/1.2058205Google Scholar
  47. 47.
    Demers JR, Logan Jr RT, Bergeron NJ, Brown ER (2008) A coherent frequency-domain THz spectrometer with a signal-to-noise ratio of 60 dB at 1 THz. Proc SPIE 6949:694909.1–9Google Scholar
  48. 48.
    Brown ER, Bjarnason JE, Fedor AM, Korter TM (2007) On the strong and narrow absorption signature in lactose at 0.53 THz. Appl Phys Lett 90 (6):061908.1–3. doi:10.1063/1.2437107Google Scholar
  49. 49.
    Majewski A, Abreu R, Wraback M (2007) A high resolution terahertz spectrometer for chemical detection. Proc SPIE 6549:65490B.1–8. doi:10.1117/12.719485Google Scholar
  50. 50.
    Majevski A, Bansleben D, Wraback M (2008) A High Resolution Terahertz Spectrometer for Chemical Detection. Paper presented at the International Symposium on Spectral Sensing Research, Hoboken, NJ, USA, 23–27 June 2008Google Scholar
  51. 51.
    Egert S, Peri D, Abramovich A (2010) Spectroscopic Study of Containers and Their Content Using a High-Resolution THz System. IEEE Sens J 10 (3):379–383. doi:10.1109/JSEN.2009.2037291CrossRefGoogle Scholar
  52. 52.
    Globus T, Parthasarathy R, Khromova T, Woolard DL, Swami N, Gatesman AJ, Waldman J (2004) Optical characteristics of biological molecules in the terahertz gap. Proc SPIE 5584:1–10. doi:10.1117/12.580838CrossRefGoogle Scholar
  53. 53.
    Parthasarathy R, Globus T, Khromova T, Swami N, Woolard D (2005) Dielectric properties of biological molecules in the Terahertz gap. Appl Phys Lett 87 (11):113901.1–3. doi:10.1063/1.2046730Google Scholar
  54. 54.
    Rønne C, Thrane L, Åstrand P-O, Wallqvist A, Mikkelsen KV, Keiding SR (1997) Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation. J Chem Phys 107 (14):5319–5331. doi:10.1063/1.474242CrossRefGoogle Scholar
  55. 55.
    Globus T, Khromova T, Gelmont B, Woolard D, Tamm LK (2006) Terahertz characterization of dilute solutions of DNA. Proc SPIE 6093:609308.1–12. doi:10.1117/12.646529Google Scholar
  56. 56.
    Rodriguez-Saona LE, Khambaty FM, Fry FS, Calvey EM (2001) Rapid Detection and Identification of Bacterial Strains by Fourier Transform Near-Infrared Spectroscopy. J Agric Food Chem 49 (2):574–579. doi:10.1021/jf000776jCrossRefGoogle Scholar
  57. 57.
    Brown ER, Khromova TB, Globus T, Woolard DL, Jensen JO, Majewski A (2006) Terahertz-Regime Attenuation Signatures in Bacillus subtilis and a Model Based on Surface Polariton Effects. IEEE Sens J 6 (5):1076–1083. doi:10.1109/JSEN.2006.881354Google Scholar
  58. 58.
    Globus T, Woolard DL, Khromova T, Partasarathy R, Majewski A, Abreu R, Hesler JL, Pan S-K, Ediss G (2004) Terahertz signatures of biological-warfare-agent simulants. Proc SPIE 5411:25–32. doi:10.1117/12.549128CrossRefGoogle Scholar
  59. 59.
    Majewski AJ, Miller P, Abreu R, Grotts J, Globus T, Brown E (2005) Terahertz signature characterization of bio-simulants. Proc SPIE 5790:74–84. doi:10.1117/12.603658CrossRefGoogle Scholar
  60. 60.
    Globus T, Woolard D, Samuels A, Khromova T, Jensen J (2003) Sub-millimeter Wave Fourier Transform Characterisation of Bacterial Spores. Paper presented at the International Symposium on Spectral Sensing Research, Santa Barbara, CA, USA, 2–6 June 2003Google Scholar
  61. 61.
    Globus T, Theodorescu D, Frierson H, Khromova T, Woolard D (2005) Terahertz spectroscopic characterization of cancer cells. Proc SPIE 5692:233–240. doi:10.1117/12.594391CrossRefGoogle Scholar
  62. 62.
    Globus T, Khromova T, Bykhovski A, Gelmont B, Woolard D (2007) Terahertz Sensing of Bio-Water Contaminents Using Vibrational Spectroscopy. Int J High Speed Electron Syst X (X):1–14Google Scholar
  63. 63.
    Dorofeeva T (2011) Characterization of Biosimulants Using Sub-THz Vibrational Spectroscopy. M. Sc., University of Virginia, CharlottesvilleGoogle Scholar
  64. 64.
    Globus T, Dorofeeva T, Sizov I, Gelmont B, Lvovska M, Khromova T, Chertihin O, Koryakina Y (2012) Sub-THz Vibrational Spectroscopy of Bacterial Cells and Molecular Components. Am J Biomed Eng 2 (4):143–154. doi:10.5923/j.ajbe.20120204.01CrossRefGoogle Scholar
  65. 65.
    Woolard DL, Brown ER, Samuels AC, Jensen JO, Globus T, Gelmont B, Wolski M Terahertz-frequency remote-sensing of biological warfare agents. In: In: IEEE Microwave Theory and Techniques Society International Microwave Symposium Digest, vol 2, Philadelphia, PA, USA, 8–13 June 2003. pp 763–766. doi:10.1109/MWSYM.2003.1212483Google Scholar
  66. 66.
    Yu B, Alimova A, Katz A, Alfano RR (2005) THz absorption spectrum of Bacillus subtilis spores. Proc SPIE 5727:20–23. doi:10.1117/12.590951CrossRefGoogle Scholar
  67. 67.
    Globus T, Ganguly G, Roca i Cabarrocas P (2000) Optical characterization of hydrogenated silicon thin films using interference technique. J Appl Phys 88 (4):1907–1915. doi:10.1063/1.1305855CrossRefGoogle Scholar
  68. 68.
    Gelmont B, Globus T, Bykhovski A, Lichtenberger A, Swami N, Parthasarathy R, Weikle R (2012) Method of Local Electro-Magnetic Field Enhancement of Terahertz (THz) Radiation in Sub Wavelength Regions and Improved Coupling of Radiation to Materials through the Use of the Discontinuity Edge Effect, US Patent 8,309, 930, 26 November 2012Google Scholar
  69. 69.
    Parthasarathy R, Bykhovski A, Gelmont B, Globus T, Swami N, Woolard D (2007) Enhanced Coupling of Subterahertz Radiation with Semiconductor Periodic Slot Arrays. Phys Rev Lett 98 (15):153906.1–4. doi:10.1103/PhysRevLett.98.153906Google Scholar
  70. 70.
    Gelmont B, Parthasarathy R, Globus T, Bykhovski A, Swami N (2008) Terahertz (THz) Electromagnetic Field Enhancement in Periodic Subwavelength Structures. IEEE Sens J 8 (6):791–796. doi:10.1109/JSEN.2008.923222CrossRefGoogle Scholar
  71. 71.
    Gelmont B, Globus T (2011) Edge Effect in Perfectly Conducting Periodic Subwavelength Structures. IEEE Trans Nanotechnol 10 (1):83–87. doi:10.1109/TNANO.2010.2064785CrossRefGoogle Scholar

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© Springer-Verlag New York 2014

Authors and Affiliations

  1. 1.University of VirginiaCharlottesvilleUSA

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