Dwight L. Woolard

THz-Spectroscopy of Biological Molecules.

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.

Terahertz Fourier transform characterization of biological materials in a liquid phase

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.

Terahertz sources and detectors and their application to biological sensing

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.

Submillimeter-wave Fourier transform spectroscopy of biological macromolecules

In this article we report experimental results on Fourier-transform infrared spectroscopy of deoxyribonucleic acid (DNA) macromolecules and related biological materials in the submillimeter range (i.e., ∼10–500 cm−1). 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−1) with a higher resolution of 0.2 cm−1 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 ...

Simulation of resonant tunneling structures: Origin of the I–V hysteresis and plateau-like structure

Hysteresis and plateau-like behavior of the I–V curves of a double-barrier resonant tunneling structure are simulated in the negative differential resistance region. Our simulation results show that the creation of an emitter quantum well after the current passes its maximum value is the key point in understanding the origin of the I–V plateau-like structure. It is demonstrated that the plateau-like behavior of the I–V curves is produced by the coupling between the energy level in the emitter quantum well and that in the main quantum well. The hysteresis is a manifestation of the above-mentioned energy level coupling, the accumulation and distribution of electrons in the emitter, and the coupling between the energy level in the quantum well and the conduction band edge or the three-dimensional continuum states in the emitter. The effects of the structural parameters on the bistability of the I–V curves of resonant tunneling devices are discussed. The creation and disappearance mechanism of the emitter qua...

Sub-millimetre wave absorption spectra of artificial RNA molecules

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.

THZ-FREQUENCY SPECTROSCOPIC SENSING OF DNA AND RELATED BIOLOGICAL MATERIALS

The terahertz frequency absorption spectra of DNA molecules reflect low-frequency internal helical vibrations involving rigidly bound subgroups that are connected by the weakest bonds, including the hydrogen bonds of the DNA base pairs, and/or non-bonded interactions. Although numerous difficulties make the direct identification of terahertz phonon modes in biological materials very challenging, recent studies have shown that such measurements are both possible and useful. Spectra of different DNA samples reveal a large number of modes and a reasonable level of sequence-specific uniqueness. This chapter utilizes computational methods for normal mode analysis and theoretical spectroscopy to predict the low-frequency vibrational absorption spectra of short artificial DNA and RNA. Here the experimental technique is described in detail, including the procedure for sample preparation. Careful attention was paid to the possibility of interference or etalon effects in the samples, and phenomena were clearly differentiated from the actual phonon modes. The results from Fourier-transform infrared spectroscopy of DNA macromolecules and related biological materials in the terahertz frequency range are presented. In addition, a strong anisotropy of terahertz characteristics is demonstrated. Detailed tests of the ability of normal mode analysis to reproduce RNA vibrational spectra are also conducted. A direct comparison demonstrates a correlation between calculated and experimentally observed spectra of the RNA polymers, thus confirming that the fundamental physical nature of the observed resonance structure is caused by the internal vibration modes in the macromolecules. Application of artificial neural network analysis for recognition and discrimination between different DNA molecules is discussed.

Millimeter wave-induced vibrational modes in DNA as a possible alternative to animal tests to probe for carcinogenic mutations

Developing methods for alternative testing is increasingly important due to dwindling funding resources and increasing costs associated with animal testing and legislation. We propose to test the feasibility of a new and novel method for detecting DNA mutagenesis using millimeter wave spectroscopy. Although millimeter wave spectroscopy has been known since the 1950s, the cost was prohibitive and studies did not extend to large biological proteins such as DNA. Recent advances have made this technology feasible for developing laboratory and field equipment. We present preliminary findings for lesion‐induced vibrational modes in DNA observed from 80 to 1000 gigahertz (GHz). These findings suggest that there are vibrational modes that can be used as identification resonances. These modes are associated with localized defects of the DNA polymers. They are unique for each defect/lesion, and should be easy to detect. We described a field‐detecting detector based on the local modes.

Determining 4H silicon carbide electronic properties through combined use of device simulation and metal–semiconductor field-effect-transistor terminal characteristics

A two-dimensional numerical device simulator has been developed specially for the recessed gate 4H silicon carbide(4H-SiC) metal–semiconductor field-effect-transistor (MESFET). By combining numerical techniques, material physics, and measured device characteristics, we are able to use the simulator to extract more information about the new material 4H-SiC, including the mobility, velocity-field curves, and the Schottky barrier height. We have also enabled and used the new simulator to investigate breakdown voltage and thus predict operation limitations of the 4H-SiC device. Simulations indicate that impact ionization is relatively small in 4H-SiC, thereby leading to a very high breakdown voltage of 125 V in a 0.7 μm gate MESFET.

Terahertz generation in submicron GaN diodes within the limited space-charge accumulation regime

The conditions for microwave power generation with hot-electron transport are investigated in a submicron GaN diode when it operates in the limited space-charge accumulation (LSA) mode. Applying a transport model based on the local quasistatic approximation, the analysis shows that the nitride diodes can support the LSA mode of oscillation in the terahertz-frequency range. For a 100nm n-GaN diode with a cross section of 500μm2 and the electron density of 1×1017cm−3, the generated microwave power is estimated to be as high as ≈0.6W with the corresponding dc-to-rf conversion efficiency of ≈9% and the negative differential resistance of ≈−1.3Ω; which thus provides an efficient mechanism to achieve very high-frequency microwave generation in the nitrides.