We demonstrate frequency domain THz anisotropy signature detection for protein crystal models using newly developed compact tunable narrow band THz sources based on Orientation Patterned Gallium Phosphide for turn-key spectroscopic systems.
We demonstrate tunable narrowband THz generation by optical rectification of a femtosecond pulse in Orientation Patterned Gallium Phosphide. Center frequencies of 0.9 - 3.8 THz with average power up to 15 μW were achieved using a 1.064 µm fiber laser for the pump laser. Biomolecular characterization for an early application of this system is also shown in this work by anisotropic spectroscopic signature detection of molecular crystals in the THz region.
Using Terahertz near field microscopy we find orientation dependent narrow band absorption features for lysozyme crystals. Here we discuss identification of protein collective modes associated with the observed features. Using normal mode calculations we find good agreement with several of the measured features, suggesting that the modes arise from internal molecular motions and not crystal phonons. Such internal modes have been associated with protein function.
We present results on design, fabrication, and characterization of hot-electron bolometers based on low-mobility
two-dimensional electron gas (2DEG) in AlInN/GaN and AlGaN/GaN heterostructures. Electrical and optical
characterization of our Hot Electron Bolometers (HEBs) show that these sensors combine (i) high coupling to incident
THz radiation due to Drude absorption, (ii) significant electron heating by the THz radiation due to small value of the
electron heat capacity, (iii) substantial sensitivity of the device resistance to the heating effect. A low contact resistance
(below 0.5 Ω·mm) achieved in our devices ensures that the THz voltage primarily drops across the active region. Due to
a small electron momentum relaxation time, the inductive part of the impedance in our devices is large, so these sensors
can be combined with standard antennas or waveguides. In the capacity of the THz local oscillator (LO) for heterodyne
THz sensing, we fabricated AlGaAs/GaAs quantum cascade lasers (QCLs) with a stable continuous-wave single-mode
operation in the range of 2.5-3 THz. Spectral properties of the QCLs have been studied by means of Fourier transform
spectroscopy. It has been demonstrated that the spectral purity of the QCL emission line doesn't exceed the spectrometer
resolution limit at the level of 0.1 cm<sup>-1</sup> (3 GHz). Discrete spectral tuning can be achieved using selective devices; fine
tuning can be done by thermally changing the refractive index of the material and by applied voltage. Compatibility of
the low-mobility 2DEG microbolometers with QCLs in terms of LO power requirements, spectral coverage, and cooling
requirements makes this technology especially attractive for THz heterodyne sensing.
Protein function is reliant on structural flexibility and this flexibility is slaved to the surrounding solvent. Here we
discuss how the exposed surface of the protein influences the solvent dynamics and thereby influences the protein's own
structural dynamics. We discuss measurements of the THz absorption of water in the presence of hydrophilic and
The vibrational modes corresponding to protein tertiary structural motion lay in the far infrared or terahertz frequency range. These collective large scale motions depend on global structure and thus will necessarily be perturbed by ligand binding events. We discuss the use of terahertz dielectric spectroscopy to measure these vibrational modes and the sensitivity of the technique to changes in protein conformation, oxidation state and environment. A challenge of
applying this sensitivity as a spectroscopic assay for ligand binding is the sensitivity of the technique to both bulk water
and water bound to the protein. This sensitivity can entirely obscure the signal from the protein or protein-ligand complex itself, thus necessitating sophisticated sample preparation making the technique impractical for industrial applications. We discuss methods to overcome this background and demonstrate how terahertz spectroscopy can be used to quickly assay protein binding for proteomics and pharmaceutical research.
The terahertz dielectric response of partially thermally denatured, hen egg white lysozyme (HEWL) films is measured as a function of frequency and hydration using terahertz time domain spectroscopy (THz-TDS). Results are compared to similar measurements on native state samples. The frequency and hydration dependence of the absorbance for the two sample types are highly similar except for a notable suppression at ~ 0.4 THz (13 cm<sup>-1</sup>) in the partially denatured sample. In contrast to the native state sample which has a nearly frequency independent index of refraction, the index of the partially denatured sample decreases as a function of frequency. A transition is observed in both the absorbance and the index at a hydration level of ~ 0.25h (grams H<sub>2</sub>O per gram lysozyme). Below the transition, the response slowly increases while above 0.25h, the slope of both the absorbance and index sharply increases. Interestingly, we observed similar behavior in the native sample. The Cole-Cole plots exhibit a hydration dependence that is distinct from the native sample and indicative of neither pure resonance nor dielectric relaxation. We consider the implications of these results on THz biomolecular sensors.
We demonstrate the use of terahertz time domain spectroscopy for determination of ligand binding for biomolecules. Vibrational modes associated with tertiary structure conformational motions lay in the THz frequency range. We examine the THz dielectric response for hen egg white lysozyme (HEWL): free and bound with tri-N-acetyl-D-glucosamine. Transmission measurements on thin films show that there is a small change in the real part of the refractive index as a function of binding and a sizable decrease in the absorbance. A phenomenological model is used to determine the source of the absorbance change. A change in the vibrational mode density of states and net dipole moment changes will necessarily happen for all biomolecule-ligand binding, thus THz dielectric measurements may provide an universally applicable method to determine probe-target binding for biosensor applications.
Terahertz (THz) absorbance measurements as a function of confirmation for bacteriorhodopsin has been performed in the steady state demonstrating the dependence on protein conformation and mutation. We introduce a new technique for performing low time resolution visible pump/THz probe measurements relevant to biomolecular systems. We will discuss the experimental protocol required for these measurements and how the THz absorbance can be used as a characterization tool for technologically important biomolecules.
Electrons in semiconductor nanostructures such as quantum wells can exhibit a highly nonlinear response to far-infrared radiation of sufficient intensity, such as can be supplied by the free-electron lasers (FELs) at UCSB. Several different physical mechanisms can cause nonlinear behavior in nanostructures. Experimental results at UCSB demonstrate that transport, absorption, and harmonic generation can be used as probes of nonlinear response. In the future, it may be possible to use the UCSB-FELs to observe completely new nonlinear phenomena, such as non-perturbative quantum resonances in quantum wells driven by intense far-infrared radiation.
Carriers confined in quantum well structures in the GaAs-Al<SUB>x</SUB>Ga<SUB>1-x</SUB>As and InAs-AlSb systems have strongly nonlinear response at far-infrared (FIR) frequencies: they are strong harmonic generators. To date, studies of FIR frequency harmonic generation from heterostructures have been limited primarily to discrete frequencies accessible by molecular gas lasers (MGL). Because the mechanisms responsible for harmonic generation are expected to have frequency dependence in the FIR, the broad, continuous frequency coverage of the free electron lasers (FEL) at UCSB (4 cm<SUP>-1</SUP> - 25 cm<SUP>-1</SUP> for the millimeter FEL, and 32 cm<SUP>-1</SUP> to 155 cm<SUP>-1</SUP> for the FIR FEL) make them ideal sources for studies of free carrier nonlinearities in heterostructures. Quantitative experiments on harmonic generation must distinguish the small harmonic signals generated by the samples from the fundamental, and from the harmonic content of the incident FEL light. Here we discuss strategies for achieving the required selectivity, preliminary data taken with an MGL on heterostructure samples, and data taken with the FEL for a suitable calibration sample, LiNbO<SUB>3</SUB>.