The terahertz frequency absorption spectraof DNA molecules reflect low-frequencyinternal helical vibrations involvingrigidly bound subgroups that are connectedby the weakest bonds, including thehydrogen bonds of the DNA base pairs,and/or non-bonded interactions. Althoughnumerous difficulties make the directidentification of terahertz phonon modes inbiological materials very challenging, ourresearch has shown that such measurementsare both possible and fruitful. Spectra ofdifferent DNA samples reveal a large numberof modes and a reasonable level ofsequence-specific uniqueness. In an attemptto show that the long wavelength absorptionfeatures are intrinsic properties ofbiological materials determined by phononmodes, a normal mode analysis has been usedto predict the absorption spectra ofpolynucleotide RNA Poly[G]-Poly[C]. Directcomparison demonstrated a correlationbetween calculated and experimentallyobserved spectra of the RNA polymers, thusconfirming that the fundamental physicalnature of the observed resonance structureis caused by the internal vibration modesin the macromolecules.In this work we demonstrate results fromFourier-Transform Infrared (FTIR)spectroscopy of DNA macromolecules andrelated biological materials in theterahertz frequency range. Carefulattention was paid to the possibility ofinterference or etalon effects in thesamples, and phenomena were clearlydifferentiated from the actual phononmodes. In addition, we studied thedependence of transmission spectra ofaligned DNA and polynucleotide film sampleson molecule orientation relative to theelectromagnetic field, showing the expectedchange in mode strength as a function ofsample orientation. Further, the absorptioncharacteristics were extracted from thetransmission data using the interferencespectroscopy technique, and a stronganisotropy of terahertz characteristics wasdemonstrated.

A detailed investigation of phonon modes in DNA macromolecules is presented. This work presents experimental evidence to confirm the presence of multiple dielectric resonances in the submillimeter-wave spectra (i.e., approximately 0.01-10 THz) obtained from DNA samples. These long-wave (i.e., approximately 1-30 cm(-1)) absorption features are shown to be intrinsic properties of the particular DNA sequence under study. Most importantly, a direct comparison of spectra between different DNA samples reveals a large number of modes and a reasonable level of sequence-specific uniqueness. This work establishes the initial foundation for the future use of submillimeter-wave spectroscopy in the identification and characterization of DNA macromolecules.

Significant progress has been achieved during the last several years relating to experimental and theoretical aspects of terahertz (or submillimetre wave) Fourier transform spectroscopy of biological macromolecules. However, previous research in this spectral range has been focused on bio-materials in solid state since it was common opinion that high water absorption will obscure the spectral signatures of the bio-molecules in solutions. At the same time, the biological functions of DNA and proteins take place in water solutions. In this work, the spectra of DNA samples have been measured in liquid phase (gel) over the spectral range 10–25 cm−1 and compared with spectra obtained from solid films. The results demonstrate that there is very little interference between the spectral features of the material under test and the water background except for the band around 18.6 cm−1. Multiple resonances due to low frequency vibrational modes within biological macromolecules in solutions are unambiguously demonstrated. Higher level of sensitivity and higher sharpness of vibrational modes are observed in the liquid environment in comparison with the solid phase, with the width of spectral lines 0.3–0.5 cm−1. Gel sample spectra are found to be polarization-dependent. The ability of THz spectroscopy to characterize samples in liquid phase could be very important since it permits examination of DNA interactions in real (wet) samples. One demonstrated example of practical importance is the ability to discriminate between spectral patterns for native and denaturated DNA.

We demonstrate submillimetre-wave Fourier transform spectroscopy as a novel technique for biological molecule characterization. Transmission measurements are reported at frequencies 10-25 cm −1 for single-and double-stranded RNA molecules of known base-pair sequences: homopolymers poly[A], poly[U], poly[C] and poly[G], and double-stranded homopolymers poly[A]-poly[U] and poly[C]-poly[G]. Multiple resonances are observed (i.e. in the microwave through terahertz frequency regime).We also present a computational method to predict the low-frequency absorption spectra of short artificial DNA and RNA. Theoretical conformational analysis of molecules was utilized to derive the low-frequency vibrational modes. Oscillator strengths were calculated for all the vibrational modes in order to evaluate their weight in the absorption spectrum of a molecule. Normal modes and absorption spectra of the double-stranded RNA chain poly[C]-poly[G] were calculated. The absorption spectra extracted from the experiment were directly compared with the results of computer modelling thereby, confirming the fact that observed spectral features result from electromagnetic wave interactions with the DNA and RNA macromolecules. Correlation between experimental spectrum and modelling results demonstrates the ability of normal mode analysis to reproduce RNA vibrational spectra.

We present a computational method which couples normal mode analysis in internal coordinates of a molecule with very far IR spectroscopy. The analytical expression for the dependence of IR absorption on frequency incorporates frequencies and optical activities of each normal mode. In order to predict far-IR spectra of a molecule we evaluate the optical activity of each normal mode. This optical activity is determined by the vibration amplitude of the dipole moment produced by a normal mode. We calculated normal modes of DNA double-helical fragments (dA) 12 á (dT) 12 and (dAdT) 6 á (dA-dT) 6 and evaluated their optical activities. These were found to be very sensitive to the DNA basepair sequence. The positions of the resonance peaks in the calculated absorption spectrum of (dA) 12 á (dT) 12 are in a good agreement with those obtained by Fourier transform IR spectroscopy (Powell JW et al. 1987 Phys Rev A 35: 3929±3939).

In this work, sub-terahertz (THz) spectroscopy is applied to characterize lyophilized and in vitro cultured bacterial cells of non-pathogenic species of Escherichia coli (E. coli) and Bacillus subtilis (BG), spores of BG and DNA fro m E. coli. One of the goals of this research is to demonstrate that Fourier Transform (FT) spectroscopy in the frequency region of 10-25 cm -1 is sensitive enough to reveal characteristic spectral features fro m bio-cells and spores in different environment, to verify the d ifferences between species, and to show the response of spores to vacuum and response of cultured cells to heat. The experimental technique was significantly improved for sensitivity and reliab ility. Observed spectra taken with a spectral resolution of 0.25 cm -1 using FT spectrometer with a detector operating at 1.7 K are rich in well resolved features having spectral widths of ~0.5-1 cm -1 . The reproducibility of experimental results was verified and confirmed. Measured spectra from E. coli DNA and from the entire cell have many similarit ies, thus demonstrating that the cellu lar co mponents might contribute to the v ibrational spectrum of the cell. The results of this work confirm that observed spectroscopic features are caused by fundamental physical mechanism of interaction between THz rad iation and biological macro-mo lecules. Particu larly, the analysis of results indicates that the spectroscopic signatures of microorganis ms originate fro m the co mbination of low frequency vibrational modes or group of modes at close frequencies (vibrational bands) within mo lecular co mponents of bacterial cells/spores, with the significant contribution from the DNA. The significance of this study is justified by necessity for a fast and effective, label free and reagent free optical technology to protect against environmental and other biological threats, as well as for general medical research. The obtained results show that THz v ibrational spectroscopy promises to add quantitative genetic information to the characteristic signatures of biological objects, increasing the detection accuracy and selectivity when appropriate spectral resolution is used.

Terahertz spectroscopy has long been used as an important measurement tool in fields such as radio astronomy, physical chemistry, atmospheric studies and plasma research. More recently terahertz technology has been used to develop an exciting new technique to investigate the properties of a wide range of biological materials. Although much research remains before a full understanding of the interaction between biomaterials and terahertz radiation is developed, these initial studies have created a compelling case for further scientific study. Also, the potential development of practical tools to detect and identify biological materials such as biological-warfare agents and food contaminants, or of medical diagnostic tools, is driving the need for improved terahertz technology. In particular, improved terahertz sources and detectors that can be used in practical spectroscopy systems are needed. This paper overviews some of the recent measurements of the terahertz spectra of biomaterials and the ongoing efforts to create an all-solid-state technology suitable not only for improved scientific experiments but also for military and commercial applications.

In this article we report experimental results on Fourier-transform infrared spectroscopy of deoxyribonucleic acid ͑DNA͒ macromolecules and related biological materials in the submillimeter range ͑i.e., ϳ10-500 cm Ϫ1 ͒. Film samples made from commercial DNA fibers, polyadenylic acid potassium salt, and cellular agents such as the spore form of Bacillus subtillis have been prepared and measured. A broad series of measurements carried out in the low frequency region ͑10-50 cm Ϫ1 ͒ with a higher resolution of 0.2 cm Ϫ1 revealed fine features-multiple dielectric resonances in the submillimeter-wave spectra obtained from DNA samples. These long-wave absorption features are shown to be intrinsic properties of biological materials determined by phonon modes. The emphasis is on reproducibility of experimental spectra and on receiving reliable results. The effects of differences in sample preparation, including sample geometry, orientation, and aging are studied and separated from the phonon effects that determine the fine structure of transmission spectra. A direct comparison of spectra between different DNA samples reveals a large number of modes and a reasonable level of sequence-specific uniqueness. A theoretical study of two double helical DNA fragments has applied a normal mode analysis to predict spectra in the far infrared. Most of the modes determined by long-distance interactions are at frequencies below 220 cm Ϫ1 , with the density higher than one mode per cm Ϫ1 , which is approximately what was observed experimentally.