Terahertz Time-domain Spectroscopy Research Articles

Different Types of Bone Fractures Observed by Terahertz Time-Domain Spectroscopy

Different Types of Bone Fractures Observed by Terahertz Time-Domain Spectroscopy

Trehalose and its dihydrate: terahertz insights from solid to solution states

Carbohydrates are pivotal biomolecules in biochemistry; this study employs terahertz time-domain spectroscopy (THz-TDS) to investigate the spectral characteristics of trehalose and its hydrate across the 0.1 to 2.2 THz frequency range. Notable differences in spectra between the two compounds were observed. Density Functional Theory (DFT) simulations of the crystal structure were conducted to elucidate this phenomenon. The consistency between experimental results and simulations substantiates the reliability of the experimental findings. Additionally, the spectral characteristics of these carbohydrates in solution were examined using microfluidic chip technology. This approach facilitates a comprehensive comparison of their behaviors in both solid and solution states.

Broadband high-contrast-grating-type waveplates for the terahertz range

The high-contrast-grating waveplates utilizing high contrast between silicon and air refractive indexes were developed in order to perform as a quarter wave and a half wave plate in the selected THz frequency range. The waveplates possessed anti-reflective properties due to the specific inclination of the walls both in parallel and in perpendicular direction to grating axis, efficiently suppressing the reflection losses caused by air-dielectric interface for both transverse magnetic and transverse electric polarizations. Moreover, significant reduction of the transmittance gap was achieved between both polarizations while mitigating overall Fabry-Perot effect. Validation of the concepts was carried out by measuring transmission amplitude and phase spectra of the fabricated samples in a broadband of THz time-domain spectroscopy and vector-network-analysis systems considering also some real applications.

Characteristic Fingerprint Spectrum of α-Synuclein Mutants on Terahertz Time-Domain Spectroscopy

ObjectiveAlpha-Synuclein (α-Syn), a presynaptic neuronal protein encoded by the SNCA gene, is involved in the pathogenesis of Parkinson's disease. Point mutations and multiplications of the α-Syn (A30P and A53T) are correlated with early-onset Parkinson's disease characterized by rapid progression and poor prognosis. Currently, the clinical identification of SNCA variants, especially disease-related A30P and A53T mutants, remains challenging and also time-consuming. This study has aimed to develop a novel label-free detection method for distinguishing the SNCA mutants using transmission terahertz (THz) time-domain spectroscopy. MethodsThe protein was spin-coated onto the quartz to form a thin film, which was measured using THz time-domain spectroscopy. The spectral characteristics of THz broadband pulse waves of α-Syn protein variants (SNCA wild type [WT], A30P, and A53T) at different frequencies were analyzed via Fourier transform. ResultsThe amplitude A intensity (AWT, AA30P, and AA53T) and peak occurrence time in THz-TDS sensitively distinguished the three protein variants. The phase φ difference in THz frequency domain followed the trend of φWT>φA30P>φA53T. There was a significant difference in THz frequency amplitude A’ corresponding to the frequency ranging from 0.4 THz to 0.66 THz (A’A53T>A’A30P>A’WT). At a frequency of 0.4-0.6 THz, the transmission T of THz waves distinguished three variants (TA53T>TA30P>TWT), while there was no difference in the transmission T at 0.66 THz. ConclusionThe SNCA wild-type protein and two mutant variants (A30P and A53T) had distinct characteristic fingerprint spectra on THz time-domain spectroscopy. This novel label-free detection method has great potential for the differential diagnosis of Parkinson's disease subtypes.

Terahertz time-domain spectroscopy as a novel tool for crystallographic analysis in cellulose: tracking lattice changes following physical treatments

AbstractThe authors’ series of studies aimed to explore the potential of terahertz time-domain spectroscopy (THz-TDS) in cellulose crystallographic studies, since THz radiation can detect most intermolecular vibrations and respond to lattice phonons. In this study, we tracked changes in four types of cellulose after ball milling. As the planetary ball milling time increases, it is observed through electron microscopy that the four types of cellulose particles are gradually destroyed into finer particles, while gel permeation chromatography can prove that the molecular weight gradually decreases after ball milling and the dispersity gradually approaches one, which indicates that the dispersion of the material was reduced. The most fascinating observation was made by THz-TDS, that is we have confirmed that after ball milling, the absorption characteristics of cellulose I and II in cellulose I treated with 10% NaOH (crystalline partial transition from cellulose I to II) exhibited an opposite trend. Specifically, the absorption of cellulose II at 2.40THz and 2.77THz increased, while the absorption of cellulose I at 2.11THz and 3.04THz decreased after ball milling, which suggests an increased conversion rate of cellulose I to cellulose II post-milling. Cellulose with different crystalline allomorphs shows different characteristic absorption in the THz region, and the peak position will not change even after the ball milling, only the absorption intensity changes. Although it can be observed through the most traditional X-ray diffraction method that the crystallinity index of all cellulose samples gradually decreases after ball milling. However, different from the THz results, the change after ball milling of cellulose I treated with 10% NaOH is only reflected in very subtle pattern changes, that is, the peak close to the 200 crystalline plane position is slightly shifted after ball milling.

Benzenehexol‐Based 2D Conjugated Metal–Organic Frameworks with Kagome Lattice Exhibiting a Metallic State

Abstract2D conjugated metal–organic frameworks (2D c‐MOFs) are emerging as unique electroactive materials for electronics and spintronics. The structural design and discovery of Kagome‐type 2D c‐MOFs exhibiting a metallic state are of paramount significance, yet remain rarely explored. Here, the solution synthesis of benzenehexol‐based 2D c‐MOFs based is presented on the tetrahydroxy‐1,4‐quinone (THQ) ligand. This study shows that controlling the pH of the reaction system to ≈7.5 yields an energetically favorable nonporous Cu3(C6O6) with a Kagome lattice, while at a pH of ≈10, the known porous Cu3(C6O6)2 with a honeycomb lattice is obtained. The crystal structures of both Cu3(C6O6)2 and Cu3(C6O6) are resolved with near‐atomic precision (resolution, 1.8 Å) using an imaging technique. Unlike the p‐type semiconducting behavior of Cu3(C6O6)2, theoretical studies identify Cu3(C6O6) as a metal due to its unique structural topology. The metallic state of Cu3(C6O6) is experimentally validated by terahertz time‐domain spectroscopy (THz‐TDS), which shows an increase in conductivity upon cooling. Scattering‐type scanning near‐field optical microscopy (s‐SNOM) measurements further support these findings by revealing an increase in normalized reflectivity with decreasing temperature. This work provides a new avenue for tailoring the structural topology of 2D c‐MOFs to attain the Kagome lattice and metallic state.

Terahertz Spectroscopy Analysis of Amyloid Fibrils Derived from Human Serum Albumin

Amyloid fibrils, also referred to as protein fibrils, represent irregular assemblies of proteins exhibiting a cross-β configuration. Terahertz radiation, a segment of the electromagnetic spectrum spanning 0.3 to 10 terahertz (THz), is known to interact with these fibrils due to their cylindrical shape. This study's objective was to explore the potential of terahertz spectroscopy as a non-invasive means to detect the progressive growth of protein fibrils. In this investigation, human serum albumin (HSA) was synthetically induced to form protein fibrils. Confirmation of fibril formation was done by fluorescence spectroscopy, Fourier transform infrared (FTIR) spectroscopy, UV-Vis spectroscopy, and Terahertz time-domain spectroscopy (THz-TDS). To initiate the process, HSA was dissolved in distilled water at a concentration of 160 µM, followed by the addition of 60% ethanol to both samples for dilution. The HSA to Cu (II) ratio was maintained at 1:1 (160 µM) for stock solutions containing Cu (II). Subsequently, each set underwent a 6-hour heating phase at 65 °C to cultivate fibrils, which were then stored at room temperature for 30, 60, and 90 days before evaluation. Incubation of human serum albumin yielded amyloid fibrils as evidenced by ThT fluorescence, FT-IR spectroscopy revealed an emergence of fibrils within the amide I bands, extending from 1630 cm⁻¹ to 1650 cm⁻¹ and UV-Vis spectroscopy disclosed the augmentation of protein fibril absorbance over the incubation period. THz spectroscopy absorbance progressively heightened with prolonged heating of the protein fibrils due to the hydration shell surrounding them. Through these spectroscopic methods, it was elucidated that the fibrillation process led to the gradual development of β-sheet and unordered helix structures as well as the potential of THz spectroscopy as non-invasive tool for detection and monitoring of amyloidal diseases, promising insights into early diagnosis and treatment strategies.

Wide-range resistivity characterization of semiconductors with terahertz time-domain spectroscopy

Wide-range resistivity characterization of semiconductors with terahertz time-domain spectroscopy

Discrimination of hydration states of hydrated salts using terahertz time-domain spectroscopy

Water-sensitive nature of terahertz radiation has been exploited here to discriminate the hydration states of different hydrated salts, such as Cobalt Chloride Hexahydrate (CoCl2.6H2O), Copper Sulfate Pentahydrate (CuSO4.5H2O), Magnesium Chloride Hexahydrate (MgCl2.6H2O), and Calcium Chloride Dihydrate (CaCl2.2H2O). Hydration states of these salts have been prepared by heating them in an oven at different temperature for specific time on the basis of thermo-gravimetric analysis. The prepared samples were analyzed using terahertz time-domain spectroscopy (THz-TDS). The variation in absorption coefficient and refractive indices of these hydrated salts in terahertz spectral regime (0.2–1.6 THz) are linked with the change of hydration states, which has been used for their discrimination. The results have been validated with X-ray diffraction analysis. The present work indicates that THz-TDs can be considered a promising technique to fulfill the ever increasing demand of the analysis of these hydrated salts.

Influence of substituting Cu2+ for Zn2+ on the crystal structure and terahertz dielectric performances of Zn1-xCuxZrNb2O8 (x = 0.000–0.050) ceramics

A series of Zn1-xCuxZrNb2O8 (x = 0.000, 0.003, 0.010, and 0.050) ceramics with low dielectric loss and intermediate dielectric constants were synthesized by a conventional solid-phase reaction method. The terahertz dielectric performances of Zn1-xCuxZrNb2O8 (x = 0.000, 0.003, 0.010, and 0.050) ceramics have been investigated by using the Rietveld refinement method, scanning electron microscopy, Raman spectroscopy, and terahertz time-domain spectroscopy. The microscopic morphology analysis shows that the appropriate amount of Cu2+ content can make the specimen have the most uniform and medium-sized grains, which can minimize the dielectric loss in the terahertz range. Raman mapping reveals that the stress distribution is not uniform in different grains or in different regions of the same grain. The internal stresses affect the interatomic distances and influence the electronic properties, thus increasing the lattice anharmonicity and dielectric losses. In addition, the dielectric constant of the specimen in the terahertz range is mainly determined by the ionic polarization. For Zn0.997Cu0.003ZrNb2O8 sintered at 1240 °C, low dielectric losses (< 4 × 10−3 @ 0.40 THz) and intermediate dielectric constant (∼22.95 @ 0.40 THz) were obtained, which make it promising for applications in terahertz dielectric filters.

Terahertz time-domain spectroscopy of nanoadditive macroscale superlubricity: Quantitative hydration investigation and deeper insight into the solid-liquid synergistic lubrication

As a promising approach, terahertz time-domain spectroscopy (THz-TDs) provides the powerful assistance for quantitatively characterizing the solid-liquid synergistic lubrication. The hydration ratio in nanoadditive solutions was calculated by terahertz dielectric spectrum, and the exact threshold for superlubricity was found as 40%. The high hydration ratio also promoted the formation of high-quality tribofilm. Besides, not all hydrogen bonds, but the solid-liquid hydrogen bond was the true answer to the nanoadditive superlubricity. Finally, a synergistic lubrication model was proposed and it gave a detailed description of the molecular states with different lubrication. This work exerts the sensitivity of THz-TDs on hydration and liquid lubrication, providing avenues for the quick assessment of superlubricity and optimal design of nanoadditive superlubricity in the future.

Radiation hardness of ultrabroadband spintronic terahertz emitters: En-route to a space-qualified terahertz time-domain gas spectrometer

The radiation hardness of ultrabroadband spintronic terahertz emitters against γ and proton irradiation is investigated. We find that irradiation doses equivalent to those experienced by a space instrument en-route to and operated on Mars have a minor effect on the performance of the emitters. In particular, the ultrawide emission spectrum ranging from 0.1–30 THz, which covers a large part of the vibrational fingerprint region, remains unchanged. These results make this emitter type highly interesting as an essential building block for broadband gas sensors based on terahertz time-domain spectroscopy for future space missions.

Terahertz Time-Domain Spectroscopy of Blood Serum for Differentiation of Glioblastoma and Traumatic Brain Injury

The possibility of the differentiation of glioblastoma from traumatic brain injury through blood serum analysis by terahertz time-domain spectroscopy and machine learning was studied using a small animal model. Samples of a culture medium and a U87 human glioblastoma cell suspension in the culture medium were injected into the subcortical brain structures of groups of mice referred to as the culture medium injection groups and glioblastoma groups, accordingly. Blood serum samples were collected in the first, second, and third weeks after the injection, and their terahertz transmission spectra were measured. The injection caused acute inflammation in the brain during the first week, so the culture medium injection group in the first week of the experiment corresponded to a traumatic brain injury state. In the third week of the experiment, acute inflammation practically disappeared in the culture medium injection groups. At the same time, the glioblastoma group subjected to a U87 human glioblastoma cell injection had the largest tumor size. The THz spectra were analyzed using two dimensionality reduction algorithms (principal component analysis and t-distributed Stochastic Neighbor Embedding) and three classification algorithms (Support Vector Machine, Random Forest, and Extreme Gradient Boosting Machine). Constructed prediction data models were verified using 10-fold cross-validation, the receiver operational characteristic curve, and a corresponding area under the curve analysis. The proposed machine learning pipeline allowed for distinguishing the traumatic brain injury group from the glioblastoma group with 95% sensitivity, 100% specificity, and 97% accuracy with the Extreme Gradient Boosting Machine. The most informative features for these groups’ differentiation were 0.37, 0.40, 0.55, 0.60, 0.70, and 0.90 THz. Thus, an analysis of mouse blood serum using terahertz time-domain spectroscopy and machine learning makes it possible to differentiate glioblastoma from traumatic brain injury.

Effect of bone age and anatomy on the variability of the bovine bone by-product by Terahertz time-domain spectroscopy and energy-dispersive X-ray microanalysis

Bone is among the main by-products of the meat and dairy livestock. Currently, in many countries, it is valorised in pet food, disposed through incineration or exported. However, thanks to its biological and mechanical properties, it could be used in several bio-based products such as coatings, packaging, phosphorous, calcium and magnesium supply, flame retardants, etc. Successful valorisations routes of discarded bones need a comprehensive characterization of the bone tissue variability with major biological factors such as age of the animal and the anatomy of the bone itself. In this study, this variability was assessed through Terahertz time-domain spectroscopy and energy dispersive X-ray microanalysis. Bones optical properties (refractive index and absorption coefficient) and main minerals (calcium and phosphorous), were determined for adult cows’ femurs and tibias, from the same breed and breeding system and in the age range 93–120 months. Clustering analysis was then carried out, by unsupervised statistical tools (Principal Component Analysis and Agglomerative Hierarchical Clustering). Results showed that the bones considered can be grouped in two classes, represented by each anatomy; besides, the anatomy was most significant than age. The refractive index increased with age and was higher for femur; the cluster of tibias was more homogeneous than femurs. The THz radiation showed to be a useful and non-destructive tool to assess bovine bones variability and also their optical properties. This radiation could be applied to the predict animal bone components (collagen and minerals) extractability so as to valorise each cluster according to its potential.

Dynamical Transition in Dehydrated Proteins.

Terahertz time-domain spectroscopy and differential scanning calorimetry were used to study the role of the dynamics of biomolecules decoupled from solvent effects. Lyophilized sucrose exhibited steadily increasing absorption with temperature as anharmonic excitations commenced as the system emerged from a deep minimum of the potential energy landscape where harmonic vibrations dominate. The polypeptide bacitracin and two globular proteins, lysozyme and human serum albumin, showed a more complex temperature dependence. Further analysis focused on the spectral signature below and above the boson peak. We found evidence of the onset of anharmonic motions that are characteristic for partial unfolding and molecular jamming in the dry biomolecules. The activation of modes of the protein molecules at temperatures comparable to the protein dynamical transition temperature was observed in the absence of hydration. No evidence of Fröhlich coherence, postulated to facilitate biological function, was found in our experiments.

Physics-assisted machine learning for THz time-domain spectroscopy: sensing leaf wetness

Signal processing techniques are of vital importance to bring THz spectroscopy to a maturity level to reach practical applications. In this work, we illustrate the use of machine learning techniques for THz time-domain spectroscopy assisted by domain knowledge based on light–matter interactions. We aim at the potential agriculture application to determine the amount of free water on plant leaves, so-called leaf wetness. This quantity is important for understanding and predicting plant diseases that need leaf wetness for disease development. The overall transmission of 12,000 distinct water droplet patterns on a plastized leaf was experimentally acquired using THz time-domain spectroscopy. We report on key insights of applying decision trees and convolutional neural networks to the data using physics-motivated choices. Eventually, we discuss the generalizability of these models to determine leaf wetness after testing them on cases with increasing deviations from the training set.

High-Density Polyethylene Custom Focusing Lenses for High-Resolution Transient Terahertz Biomedical Imaging Sensors.

Transient terahertz time-domain spectroscopy (THz-TDS) imaging has emerged as a novel non-ionizing and noninvasive biomedical imaging modality, designed for the detection and characterization of a variety of tissue malignancies due to their high signal-to-noise ratio and submillimeter resolution. We report our design of a pair of aspheric focusing lenses using a commercially available lens-design software that resulted in about 200 × 200-μm2 focal spot size corresponding to the 1-THz frequency. The lenses are made of high-density polyethylene (HDPE) obtained using a lathe fabrication and are integrated into a THz-TDS system that includes low-temperature GaAs photoconductive antennae as both a THz emitter and detector. The system is used to generate high-resolution, two-dimensional (2D) images of formalin-fixed, paraffin-embedded murine pancreas tissue blocks. The performance of these focusing lenses is compared to the older system based on a pair of short-focal-length, hemispherical polytetrafluoroethylene (TeflonTM) lenses and is characterized using THz-domain measurements, resulting in 2D maps of the tissue refractive index and absorption coefficient as imaging markers. For a quantitative evaluation of the lens effect on the image resolution, we formulated a lateral resolution parameter, R2080, defined as the distance required for a 20-80% transition of the imaging marker from the bare paraffin region to the tissue region in the same image frame. The R2080 parameter clearly demonstrates the advantage of the HDPE lenses over TeflonTM lenses. The lens-design approach presented here can be successfully implemented in other THz-TDS setups with known THz emitter and detector specifications.

Pattern identification of kerosene-water two-phase flow in Y-shaped microchannels using terahertz spectroscopy

In this paper, the terahertz time-domain spectroscopy (THz-TDS) is proposed to investigate the behavior underlying kerosene-water two-phase flow in Y-shaped rectangular microchannels. The microchannel is initially saturated with water and water forms an external continuous phase at low kerosene flow velocities (vk), while a dispersed phase is formed at high vk. The flow process of kerosene-water two-phase flow in microchannel was in situ monitored using a THz-TDS peak intensity, and four flow patterns such as droplet flow, plug flow, slug flow and deformed interface flow are identified over a wide range of vk from 2.08 to 43.13 cm/s at selected water flow velocity (vw) of 13.96 cm/s and 27.71 cm/s. Due to the strong dependence of flow patterns on the vw, only droplet, plug and slug flows are observed at high vw. In addition, with the vw increasing from13.96 cm/s to 27.71 cm/s the ranges of vk for droplet flow and plug flow patterns are expended by ∼100%. A parameter β = k/vw, where k is the slop of the peak intensity of THz-TDS against vk, was proposed to characterize the kerosene-water two-phase flow patterns, and each β only corresponded to one phase for various vk at different vw. These results render THz-TDS a feasible technology for investigating the behavior of oil-water two-phase flow inside microfluidic devices and lay the foundation for experimental and numerical investigations on multiphase flow in microchannels for further study.

Quantitative assessment whole-rock iron content in magnetite protolith based on terahertz time-domain spectroscopy.

Terahertz time-domain spectroscopy was first used to establish a correlation with the whole-rock iron (TFe) content in different depths of the Bayan Obo protolith. Compared with element content obtained by the traditional method of X-ray fluorescence spectroscopy (XRF), a similar tendency of the absorption coefficient and refractive index is presented. Furthermore, three machine learning algorithms, namely, partial least squares regression (PLSR), random forest (RF), and multi-layer perceptron (MLP), were used to develop a quantitative analytical model for TFe content of the protolith minerals. Among the three algorithms, MLP has the highest detection accuracy, with a model coefficient of determination R 2 reaching up to 0.945. These findings demonstrate that terahertz time-domain spectroscopy can be used to rapidly quantify the TFe elemental content of protolith, providing a method of detecting the content of mineral components.

Microfluidic technology combined with density functional theory for investigating terahertz spectral characteristics of hyaluronic acid and its constituent monomers

Terahertz spectroscopy offers a valuable approach for material research, particularly in identifying unique characteristics of biological macromolecules within the terahertz band. Hyaluronic acid, a polysaccharide involved in vital life processes within the human body, holds significant application potential in medicine and healthcare. In this study, we employed a terahertz time-domain spectroscopy system combined with microfluidic chip to investigate the terahertz absorption spectra of hyaluronic acid and its constituent monomers, namely D-glucuronic acid and N-acetylglucosamine. The analysis covered solid state under vacuum and humidity of 19.8% environment , as well as solution state, spanning a frequency range of 0.5 ∼ 2.5 THz. In addition, using CASTEP software package and PBE density functional, the molecular structures of D-glucuronic acid and N-acetylglucosamine were simulated using periodic boundary conditions, and the vibrational modes of absorption peaks were assigned to determine their sources. The results indicate that terahertz spectroscopy is highly sensitive to the structure and environment of substances, and the absorption peaks of materials in a vacuum are primarily attributed to interactions both between molecules and within molecules.