Recently we introduced a Sub-THz spectroscopic system for characterizing vibrational resonance features from
biological materials. This new, continuous-wave, frequency-domain spectroscopic sensor operates at room temperature
between 315 and 480 GHz with spectral resolution of at least 1 GHz and utilizes the source and detector components
from Virginia Diode, Inc. In this work we present experimental results and interpretation of spectroscopic signatures
from bacterial cells and their biological macromolecule structural components. Transmission and absorption spectra of
the bacterial protein thioredoxin, DNA and lyophilized cells of <i>Escherichia coli (E. coli)</i>, as well as spores of <i>Bacillus
subtillis</i> and <i>B. atrophaeus</i> have been characterized. Experimental results for biomolecules are compared with absorption
spectra calculated using molecular dynamics simulation, and confirm the underlying physics for resonance spectroscopy
based on interactions between THz radiation and vibrational modes or groups of modes of atomic motions. Such
interactions result in multiple intense and narrow specific resonances in transmission/absorption spectra from nano-gram
samples with spectral line widths as small as 3 GHz. The results of this study indicate diverse relaxation dynamic
mechanisms relevant to sub-THz vibrational spectroscopy, including long-lasting processes. We demonstrate that high
sensitivity in resolved specific absorption fingerprints provides conditions for reliable detection, identification and
discrimination capability, to the level of strains of the same bacteria, and for monitoring interactions between
biomaterials and reagents in near real-time. Additionally, it creates the basis for the development of new types of
advanced biological sensors through integrating the developed system with a microfluidic platform for biomaterial
Radiation in the Terahertz frequency range interacts with vibrations in the weakest molecular couplings such as hydrogen bonding, van der Waals forces, and hydrophobic interactions. The work presented demonstrates our efforts towards the development of a microfluidic device as the sample cell for presenting liquid samples within the detection region of a novel sub-THz spectrometer. The continuous-wave, frequency-domain spectrometer, operating at room temperature between 315 and 480 GHz with spectral resolution of 0.3 GHz, already demonstrated highly intense and specific signatures from nanogram samples of dry biological molecules and whole bacterial cells. The very low absorption by water in this sample cell will allow for the use of liquid samples to present cells and molecules in their natural environment. The microfluidic device design utilizes a set of channels formed with metal sidewalls to enhance the interaction between the THz radiation and the sample, increasing the sensitivity of the system. Combined with near field effects, through use of a detection probe close to the surface of the sample cell, spatial resolution less than the diffraction limit can be achieved, further reducing the amount of sample required for analysis. This work focuses on the design, and fabrication methods, which will allow implementation of the microfluidic sample cell device within the THz spectrometer. The device will be utilized for characterization of different cell types, showing that THz interrogation of liquid samples is possible.
We investigated resonance spectroscopic features from several widely used explosives materials including RDX and
PETN in the low THz range with the goal of understanding the mechanism of interaction between radiation and material
in the form of solid films, gels and dilute solutions (suspensions). FTIR spectroscopy was used to measure spectra in
transmission and reflection modes. We demonstrated that very small amount of material with a simple sample
preparation technique can be used still providing very accurate results. Spectral features are specific not only for main
ingredients but for modifications with different plasticizers. The consistency of results for different amount of material
was observed. Computational modeling confirmed the lowest frequency modes.
In this work we present the results on combined experimental and computational study of sub-THz spectra of
liquid water. The important new result is the detection of hydrogen bonds in liquid water. The experimental
study was performed by employing Fourier Transform terahertz (THz) spectroscopy with spectral resolution of
0.25 cm<sup>-1</sup>. Resonance features in transmission spectra of water layers between thin film substrates are
demonstrated in the sub-THz range. The theoretical approach for computer simulation of THz absorption
spectra from liquid water is also discussed. The molecular dynamical (MD) simulations of water were
performed using Amber 8 and the TIP3P, SPCE (Extended Single Point Charge) and TIP4P water models.
Several examples of modeling results are presented. The experimental spectra are compared with the
theoretical predictions. The SPCE model better correlates with experimental spectra compare to two other
The development of an effective biological (bio) agent detection capability based upon terahertz (THz) frequency absorption spectra will require insight into how the constituent cellular components contribute to the overall THz signature. In this work, the specific contribution of ribonucleic acid (RNA) to THz spectra is analyzed in detail. Previously, it has only been possible to simulate partial fragments of the RNA (or DNA) structures due to the excessive computational demands. For the first time, the molecular structure of the entire transfer RNA (tRNA) molecule of <i>E. coli</i> was simulated and the associated THz signature was derived theoretically. The tRNA that binds amino acid tyrosine (tRNAtyr) was studied. Here, the molecular structure was optimized using the potential energy minimization and molecular dynamical (MD) simulations. Solvation effects (water molecules) were also included explicitly in the MD simulations. To verify that realistic molecular signatures were simulated, a parallel experimental study of tRNAs of <i>E. coli </i>was also conducted. Two very similar molecules, valine and tyrosine tRNA were investigated experimentally. Samples were prepared in the form of water solutions with the concentrations in the range 0.01-1 mg/ml. A strong correlation of the measured THz signatures associated with valine tRNA and tyrosine tRNA was observed. These findings are consistent with the structural similarity of the two tRNAs. The calculated THz signature of the tyrosine tRNA of <i>E. coli</i> reproduces many features of our measured spectra, and, therefore, provides valuable new insights into
The electro-optical properties of organic and bio-molecules have been previously investigated that have potential for selectively filtering and controlling the transmission of electromagnetic signals with carrier frequency in the THz band. Specifically, retinal isomers have been studied because they exhibit the type of THz characteristics needed for the design of molecular electronic devices. Here, the goal is to define bio-molecular filters that have utility in integrated platforms for sensing THz spectral signatures. According to our calculations, retinal isomers demonstrate the type of properties needed for the design of molecule-based optically-controllable filters in THz region. An initial challenge for this type of bio-architecture is the integration of the retinal-based components into conventional semiconductor devices. This paper presents a potential methodology for achieving such integrated sensor components. In particular, by modifying one end of retinal with a thiol linker, it is possible to chemically graft the retinal to gold surfaces. Therefore, since two-dimensional gold nanostructure arrays can be produced by depositing gold onto pit-patterned highly oriented pyrolytic graphite (HOPG) surface or semiconductor substrates, this approach could be applied to achieve large-scale integration of bio-molecular devices. This paper will report on simulations of ground state and metastable state energies, along with the associated THz spectra of the retinal isomeric molecule connected to a gold atom via the link of a cysteine molecule. In addition to the retinal isomers, this paper also investigates another isomer trans- and cis- stilbene and presents results suggesting that stilbene may also be a good candidate for molecular electronics. Hence, this paper provides results for the THz spectral characteristics and required optical excitations for a novel type of bio-device for sensing.
A novel optically-triggered (OT) interband resonant-tunneling-diode (I-RTD) device (based on AlGaSb/InAs/AlGaSb
heterostructures) concept for generating terahertz (THz) frequency oscillations has been previously presented that shows
promise for achieving enhanced output power levels under pulsed operation. The main concept is to utilize novel
nanoscale mechanisms to achieve an externally driven relaxation oscillation that consists of two phases. Namely, the
first phase is a valence band (VB) well hole-charging transient produced by a natural Zener (interband) tunneling
process and the second is a discharging transient induced by optical annihilation of the VB well hole-charge by
externally-injected photon flux. While the initial simulation results for a practical diode-laser implementation clearly
show the superiority of this new oscillator concept (i.e., excellent output power capability, ~10mW, over broad portions
of the THz regime, ~300-600GHz), the specific optical-triggering conditions required by the AlGaSb/InAs based
material systems (i.e., photonic-energy ~4.7 μm, intensity level ~3.5x10<sup>7</sup> W/cm<sup>2</sup> and a pulse repetition frequency (PRF)
equal to the THz oscillation period) are technically too demanding to meet for continuous-wave (CW) mode operation.
Hence, this paper will report on variations and extensions of the original OT-I-RTD oscillator concept. Specifically,
modifications to the device structure will be considered to allow for OT operation at 1.55 μm where the optical
technology is more robust. Here the specific focus will be in the introduction of In<sub>1-x</sub>Ga<sub>x</sub>As /GaSb<sub>y</sub>As<sub>1-y</sub> hetero-systems
and the application of band-engineering to assess the potential of a 1.55 μm based OT-I-RTD oscillator design.
Only few studies have attempted to characterize biological materials by THz spectroscopy. Most of these used either solid samples or biological tissues. In this work, we present results of THz spectroscopic characterization of dilute solutions of DNA samples. Water and heavy water (D<sub>2</sub>O) have strong absorbance that overlap significantly with important absorption bands of biomolecules in conventional FTIR spectroscopy. Cumbersome spectral subtractions and highly concentrated samples are therefore required to partially overcome problems of water interference in FTIR spectra of biomolecules. Although liquid water absorbs and contributes to
background in the THz spectral range of interest, the level of water absorption in the low THz range is at least 2.5 orders of magnitude less than in the far IR. Here, we demonstrate that reproducible spectra of dilute solutions of DNA in the frequency range 10-24 cm<sup>-1</sup> can be obtained. We show that dilute aqueous samples of DNA produce THz spectra with signals that do not overlap with those of water. This is a significant achievement towards the goal of developing THz resonance spectroscopy as a useful tool for the biological sciences because all biological functions of DNA and proteins take place in aqueous environments. A simple technique for sample preparation and characterization is described. Samples containing as little as 100 ng of DNA in 10 μl of water (0.01 mg/ml or 0.001%) have been prepared and measured. The signal/noise ratios of THz spectra of these samples are sufficient to detect reproducible resonances at several characteristic frequencies. The effect of orientation on different substrates and the mechanism of sensitivity enhancement in these samples is discussed. It should be possible to extend these methods to also study proteins in dilute solutions. Advantages of using dilute samples include small quantities of biological material required, the absence of interference from interactions between neighboring molecules, and the absence of problems with light-scattering that are often encountered with short wave-length optical techniques.
A new concept is presented for realizing midwave-infrared vertical- cavity lasers based on an interband-resonant-tunneling-diode (I-RTD). Model equations are derived in terms of material and structure parameters for predicting the output power in an I-RTD laser device constructed of InAs/AlGaSb layers. Simulation made for midwave- infrared lasers suggest that the radiation output density power in this I-RTD laser can be achieved of the order of 40 W/cm<sup>2</sup>.
The double-barrier AlGaSb/InAs/AlGaSb heterostructure with staggered bandgap alignment can admit significant interband tunneling current in addition to the conduction band electron transport. The resulting positive hole-charge accumulation in the right valence-band (VB) well will electrostatically modify the spatial potential profile across the device structure, thereby effectively altering the conduction of conduction-band electron transport. A sequentially triggered optical discharging process can be used to annihilate, or substantially reduce, the trapped holes that are generated from the interband tunneling process. Hence, an artificially induced electro-optic interaction can be used to return the device to its initial state and to produce a two-cycle oscillation process - i.e., one with a interband-induced charging transient followed by a optically-induced discharging transient to the initial state. These charging-discharging cycles obtained from this hybrid type of interband resonant-tunneling-diode (I-RTD) device constitute steady-state oscillatory behavior at very high frequency and produce alternating-current (ac) power as long as very short (i.e., sub-picosecond) and intense far-infrared laser pulses are presented to the diode. Initial studies of non-optimized structures and designs predict impressive figures of merit for oscillation frequencies (e.g., ~ 300-600 GHz) and substantial output powers (e.g., ~ 10 mW) for very modest device areas (i.e., 100 μm<sup>2</sup>). This paper will present physics-based I-RTD diode simulation results to precisely describe transport dynamics and transient electric current for both charging (initiated by Zener tunneling) and discharging (artificially induced by photons flux) processes. A basic electro-optical design concept and modeling approach for the analysis and synthesis of non-linear hybrid I-RTD circuits will also be presented. The main objectives of this paper are: (1) to perform a detailed assessment of the ac output power and efficiency of an optically-triggered (OT) I-RTD hybrid oscillator in the frequency range approximately 300 to 600 GHz, and (2) to prescribe the general requirements for realizing a diode-laser pair upon a single solid-state platform in the future. Therefore, guidelines for a practical engineering implementation and performance estimates for an OT-I-RTD hybrid oscillator design will be presented.
The development of efficient biological agent detection techniques requires in-depth understanding of THz absorption spectral features of different cell components. Chromosomal DNA, RNAs, proteins, bacterial cell wall, proteinaceous coat might be essential for bacterial cells and spores THz signature. As a first step, the DNA's contribution into entire cell THz spectra was analyzed.
The experimental study of cells and DNAs of <i>E. coli</i> and cells/spores and DNA of <i>Bacillus subtilis</i> was conducted. Samples were prepared in the form of water solutions (suspension) with the concentrations in the range 0.01-1 mg/ml. The measurable difference in the THz transmission spectra of <i>E. coli</i> and <i>Bacillus subtilis</i> DNAs was observed. The correlation between chromosomal DNA signature and a corresponding entire spore/cell signature was observed. This correlation was especially pronounced for spores of <i>Bacillus subtilis</i> and their DNA. These experimental results justify our approach to develop a model for THz signatures of biological simulants and agents. In parallel with the experimental study, for the first time, the computer modeling and simulation of chromosome DNAs of <i>E. coli</i> and <i>Bacillus subtilis</i> was performed and their THz signatures were calculated. The DNA structures were optimized using the Amber software package. Also, we developed the initial model of the DNA fragment poly(dAT)-poly(dTA) solvated in water to be used in the simulations of genetic material (DNA and RNA) of spores and cells. Molecular dynamical simulations were conducted using explicit solvent (3-point TIP3P water) and implicit solvent (generalized Born) models. The calculated THz signatures of <i>E. coli</i> and <i>Bacillus subtilis</i> DNAs and poly(dAT)-poly(dTA) reproduce many features of our measured spectra. The results of this study demonstrate that THz Fourier transform infrared spectroscopy is a promising tool in generating spectral data for complex biological objects such as bacterial cells and spores.
A biological(bio)-molecular inspired electronic architecture is presented that offers the potential for defining nanoscale sensor platforms with enhanced capabilities for sensing terahertz (THz) frequency bio-signatures. This architecture makes strategic use of integrated biological elements to enable communication and high-level function within densely-packed nanoelectronic systems. In particular, this architecture introduces a new paradigm for establishing hybrid Electro-THz-Optical (ETO) communication channels where the THz-frequency spectral characteristics that are uniquely associated with the embedded bio-molecules are utilized directly. Since the functionality of this architecture is built upon the spectral characteristics of bio-molecules, this immediately allows for defining new methods for enhanced sensing of THz bio-signatures. First, this integrated sensor concept greatly facilitates the collection of THz bio-signatures associated with embedded bio-molecules via interactions with the time-dependent signals propagating through the nanoelectronic circuit. Second, it leads to a new Multi-State Spectral Sensing (MS3) approach where bio-signature information can be collected from multiple metastable state conformations. This paper will also introduce a new class of prototype devices that utilize THz-sensitive bio-molecules to achieve molecular-level sensing and functionality. Here, new simulation results are presented for a class of bio-molecular components that exhibit the prescribed type of ETO characteristics required for realizing integrated sensor platforms. Most noteworthy, this research derives THz spectral bio-signatures for organic molecules that are amenable to photo-induced metastable-state conformations and establishes an initial scientific foundation and design blueprint for an enhanced THz bio-signature sensing capability.
Significant progress has been achieved during the last several years relating to experimental and theoretical aspects of Terahertz (or Sub-millimeter wave) Fourier transform spectroscopy of biological macromolecules. Multiple resonance due to low frequency vibrational modes within biological macromolecules have been unambiguously
demonstrated. However till now only solid films of bio-materials have been used for experimental characterization in this spectral range since it was common opinion that high water absorption will prevent from receiving the information on bio-molecules in a liquid phase. At the same time, all biological function of DNA and proteins take place in water solutions. In this work spectra of DNA samples and proteins have been measured in liquid phase (gel) in a spectral range
10-25 cm<sup>-1</sup> and compared with spectra obtained from solid films. The results demonstrate that there is almost no interference between spectral features of material in test and water background except for the band around 18.6 cm<sup>-1</sup>. Much higher level of sensitivity and higher sharpness of vibrational modes in liquid environment in comparison with solid phase is observed with the width of spectral lines 0.3-0.5 cm<sup>-1</sup>. Gel samples demonstrate effects of polarization. The ability of THz spectroscopy to characterize samples in liquid phase could be very important since it permits to look at DNA interactions, protein-protein interactions in real (wet) samples. One demonstrated example of practical
importance is the ability to discriminate between spectral patterns for native and denaturated DNA.
Low-frequency phonon modes of DNA and RNA molecules can serve as a signature of their structure, flexibility and, hence, their biological function. To investigate the relationship between RNA structure and far IR absorption spectra, we performed FTIR measurements on RNA molecules with known sequence in the spectral range from 10 cm<SUP>-1</SUP> to 25 cm<SUP>-1</SUP> and calculated their internal vibrations. To understand which phonon modes are determined by a double helical topology of nucleic acids, we compared the spectra of single stranded and double stranded RNA molecules. Homopolymers PolyA, polyU, polyC, and polyG, and double stranded homopolymers PolyA-polyU and polyC-polyG were investigated. Theoretical conformational analysis of the double stranded RNA molecules was performed and utilized to calculate the low-frequency vibrational modes. Conformational energy was minimized in the space of internal coordinates of a molecule using standard A-helical topology as an initial approximation. Normal modes were calculated as eigenfrequencies and eigenvectors of the matrix of energy second derivatives. Oscillator strengths were calculated for all the vibrational modes in order to evaluate their weight in the absorption spectrum of a molecule. The obtained phonon modes were convoluted to derive the far IR spectrum of a molecule. These predicted spectra were compared to those obtained by FTIR spectroscopy. Our results confirm that very far IR absorption spectra of biopolymers reflect specific dynamical properties resulting from their structure and topology and, therefore, can be used as fingerprints for specific molecules.
A simple and rapid self-matching modified harmonic-balance technique for submillimeter-wave Schottky-diode harmonic multipliers is presented. This work combines the physically accurate diode model with a modified harmonic-balance algorithm to determine diode-circuit design that maximize power generation and/or power efficiency in the second harmonic. The modified harmonic-balance method utilizes a novel strategy where maximum-available diode power at second-harmonic. The modified harmonic-balance method utilizes a novel strategy where maximum-available diode power at second-harmonic frequency is first derived independently and then the corresponding higher harmonic voltages and currents are determined. This approach allows for the rapid determination of the matched embedding circuit and an optimized multiplier design. A direct comparison to traditional schemes is given to illustrate the general utility of this physics-based simulation. Specifically, this work demonstrates a computationally efficient and accurate physical description as well as a more robust approach for circuit optimization.