Terahertz Pulsed Spectroscopy Research Articles

Quantitative polarization-sensitive super-resolution solid immersion microscopy reveals biological tissues’ birefringence in the terahertz range

Terahertz (THz) technology offers a variety of applications in label-free medical diagnosis and therapy, majority of which rely on the effective medium theory that assumes biological tissues to be optically isotropic and homogeneous at the scale posed by the THz wavelengths. Meanwhile, most recent research discovered mesoscale (sim lambda ) heterogeneities of tissues; lambda is a wavelength. This posed a problem of studying the related scattering and polarization effects of THz-wave–tissue interactions, while there is still a lack of appropriate tools and instruments for such studies. To address this challenge, in this paper, quantitative polarization-sensitive reflection-mode THz solid immersion (SI) microscope is developed, that comprises a silicon hemisphere-based SI lens, metal-wire-grid polarizer and analyzer, a continuous-wave 0.6 THz (lambda = 500 µm) backward-wave oscillator (BWO), and a Golay detector. It makes possible the study of local polarization-dependent THz response of mesoscale tissue elements with the resolution as high as 0.15 lambda . It is applied to retrieve the refractive index distributions over the freshly-excised rat brain for the two orthogonal linear polarizations of the THz beam, aimed at uncovering the THz birefringence (structural optical anisotropy) of tissues. The most pronounced birefringence is observed for the Corpus callosum, formed by well-oriented and densely-packed axons bridging the cerebral hemispheres. The observed results are verified by the THz pulsed spectroscopy of the porcine brain, which confirms higher refractive index of the Corpus callosum when the THz beam is polarized along axons. Our findings highlight a potential of the quantitative polarization THz microscopy in biophotonics and medical imaging.

Moisture adsorption by porous terahertz optical materials: a case study of artificial SiO2 opals

Artificial opals fabricated by sedimentation and self-assembly of colloidal SiO2 nanoparticles and annealed at different temperatures were recently considered favorable terahertz (THz) optical materials with manageable optical properties. However, interactions between such a porous material and water vapour in a humid atmosphere can hamper their THz applications due to the related changes in the material parameters and additional power loss. To quantify such an effect, in this paper, moisture adsorption by artificial SiO2 opals is studied using THz pulsed spectroscopy. Particularly, opals of two kinds were sedimented from the colloidal suspension of 300-nm-diameter SiO2 nanoparticles with different intraglobular structures and porosity. They were annealed at temperatures of 200–800°C aimed at changing their internal structure, porosity, and THz optical properties. Opals were dehydrated in a vacuum and then exposed to a humid atmosphere with 82.0 ± 2.0% relative humidity, while their THz complex dielectric permittivity was evaluated in situ in the 0.5–2.5 THz range. The observed changes in the THz dielectric curves were analyzed using the sum rule and the adsorption kinetics models. Our findings reveal a strong dependence of the THz dielectric response, amount of adsorbed water, and adsorption time constant on the opal type and annealing conditions. This effect has a general character: it can hamper real-live applications of a variety of porous THz optical materials and, thus, should be taken into account during their synthesis.

PEG-fibrin conjugates: the PEG impact on the polymerization dynamics.

Fibrin and its modifications, particularly those with functionalized polyethylene glycol (PEG), remain highly attractive as a biomaterial in drug delivery and regenerative medicine. Despite the extensive knowledge of fibrinogenesis, there is little information on the processes occurring after its modification. Previously, we found structural differences between native fibrin and its conjugates with PEG that allows us to hypothesize that a combination of methods such as terahertz (THz) pulsed spectroscopy and rheology may contribute to the characterization of gelation and reveal the effect of PEG on the polymerization dynamics. Compared to native fibrin, PEGylated fibrins had a homogenously soft surface; PEGylation also led to a significant decrease in the gelation time: from 42.75 min for native fibrin to 31.26 min and 35.09 min for 5 : 1 and 10 : 1 PEGylated fibrin, respectively. It is worth noting that THz pulsed spectroscopy makes it possible to reliably investigate only the polymerization process itself, while it does not allow us to observe statistically significant differences between the distinct PEGylated fibrin gels. The polymerization time constant of native fibrin measured by THz pulsed spectroscopy was 14.4 ± 2.8 min. However, it could not be calculated for PEGylated fibrin because the structural changes were too rapid. These results, together with those previously reported, led us to speculate that PEG-fibrin conjugates formed homogenously distributed highly water-shelled aggregates without bundling compared to native fibrin, ensuring rapid gelation and stabilization of the system without increasing its complexity.

Quantification of solid-phase chemical reactions using the temperature-dependent terahertz pulsed spectroscopy, sum rule, and Arrhenius theory: thermal decomposition of α-lactose monohydrate

Transformations of the low-energy vibrational spectra are associated with structural changes in an analyte and closely related to the instability of weak chemical bounds. Terahertz (THz)/far-infrared optical spectroscopy is commonly used to probe such transformation, aimed at characterization of the underlying solid-phase chemical reactions in organic compounds. However, such studies usually provide quite qualitative information about the temperature- and time-dependent parameters of absorption peaks in dielectric spectra of an analyte. In this paper, an approach for quantitative analyses of the solid-phased chemical reactions based on the THz pulsed spectroscopy was developed. It involves studying an evolution of the sample optical properties, as a function of the analyte temperature and reaction time, and relies on the classical oscillator model, the sum rule, and the Arrhenius theory. The method allows one to determine the temperature-dependent reaction rate V1(T) and activation energy Ea. To demonstrate the practical utility of this method, it was applied to study α-lactose monohydrate during its temperature-induced molecular decomposition. Analysis of the measured THz spectra revealed the increase of the reaction rate in the range of V1 ≃ ~9 × 10-4-10-2 min-1, when the analyte temperature rises from 313 to 393 K, while the Arrhenius activation energy is Ea ≃ ~45.4 kJ/mol. Thanks to a large number of obtained physical and chemical parameters, the developed approach expands capabilities of THz spectroscopy in chemical physics, analytical chemistry, and pharmaceutical industry.

Investigation of Formalin-Fixed Tissue Optical Characteristics in the Range of 200–500 GHz Using Pulsed Terahertz Reflection Spectroscopy to Differentiate Oral Malignant, Benign, and Cyst

The application of Terahertz electromagnetic waves to diagnose oral cancer was investigated. A single case of formalin-fixed oral squamous cell carcinoma (malignant), ameloblastoma (benign), and odontogenic keratocyst was examined using terahertz pulsed spectroscopy in the frequency span of 0.1–2 THz. The measured absorption coefficient, refractive index, and the extinction coefficient were reported to be high for malignant samples than benign and cyst. The THz results are validated with hematoxylin and eosin-stained microscopic images. The results demonstrate that the THz signal was shown to be consistently higher for the malignant sample compared to benign and the cyst. These results indicate that THz signals responded to the cell density by eliminating the effect of water.

Optical characteristics of LaNiO3 thin films in the terahertz–infrared frequency range

Transparent semiconducting oxides are widely used as conductive electrodes in optoelectronic devices in the near-infrared and visible ranges. However, their applications in the THz frequency range devices are limited because of the absorption by free carriers in this range and the low-frequency tail of the optical phonon modes. In this study, we investigated the optical and electrodynamic parameters of lanthanum nickelate films using contactless and nondestructive methods, including submillimeter coherent spectroscopy, terahertz pulsed spectroscopy, and infrared Fourier transform spectroscopy. Evidently, the film transmission deviates from the Hagen–Rubens relation by as much as 30%, and the temperature dependence of the conductivity exhibits a dominantly semiconducting behavior. A decrease in the plasma frequency of the free carriers to approximately 2000 cm−1 (0.25 eV) increases the intensity of the vibrational absorption bands of the film. Further, films with a reduced conductivity and a thickness of 100–200 nm are expected to transmit at least half of the incident radiation in the THz range. These results demonstrate the prospect of employing lanthanum nickelate films with decreased conductivity as electrode layers in optoelectronic converters in the THz frequency range.

Moisture adsorption by decellularized bovine pericardium collagen matrices studied by terahertz pulsed spectroscopy and solid immersion microscopy.

In this paper, terahertz (THz) pulsed spectroscopy and solid immersion microscopy were applied to study interactions between water vapor and tissue scaffolds-the decellularized bovine pericardium (DBP) collagen matrices, in intact form, cross-linked with the glutaraldehyde or treated by plasma. The water-absorbing properties of biomaterials are prognostic for future cell-mediated reactions of the recipient tissue with the scaffold. Complex dielectric permittivity of DBPs was measured in the 0.4-2.0 THz frequency range, while the samples were first dehydrated and then exposed to water vapor atmosphere with 80.0 ± 5.0% relative humidity. These THz dielectric measurements of DBPs and the results of their weighting allowed to estimate the adsorption time constants, an increase of tissue mass, as well as dispersion of these parameters. During the adsorption process, changes in the DBPs' dielectric permittivity feature an exponential character, with the typical time constant of =8-10 min, the transient process saturation at =30 min, and the tissue mass improvement by =1-3%. No statistically-relevant differences between the measured properties of the intact and treated DBPs were observed. Then, contact angles of wettability were measured for the considered DBPs using a recumbent drop method, while the observed results showed that treatments of DBP somewhat affects their surface energies, polarity, and hydrophilicity. Thus, our studies revealed that glutaraldehyde and plasma treatment overall impact the DBP-water interactions, but the resultant effects appear to be quite complex and comparable to the natural variability of the tissue properties. Such a variability was attributed to the natural heterogeneity of tissues, which was confirmed by the THz microscopy data. Our findings are important for further optimization of the scaffolds' preparation and treatment technologies. They pave the way for THz technology use as a non-invasive diagnosis tool in tissue engineering and regenerative medicine.

Terahertz dielectric spectroscopy and solid immersion microscopy of ex vivo glioma model 101.8: brain tissue heterogeneity.

Terahertz (THz) technology holds strong potential for the intraoperative label-free diagnosis of brain gliomas, aimed at ensuring their gross-total resection. Nevertheless, it is still far from clinical applications due to the limited knowledge about the THz-wave-brain tissue interactions. In this work, rat glioma model 101.8 was studied ex vivo using both the THz pulsed spectroscopy and the 0.15λ-resolution THz solid immersion microscopy (λ is a free-space wavelength). The considered homograft model mimics glioblastoma, possesses heterogeneous character, unclear margins, and microvascularity. Using the THz spectroscopy, effective THz optical properties of brain tissues were studied, as averaged within the diffraction-limited beam spot. Thus measured THz optical properties revealed a persistent difference between intact tissues and a tumor, along with fluctuations of the tissue response over the rat brain. The observed THz microscopic images showed heterogeneous character of brain tissues at the scale posed by the THz wavelengths, which is due to the distinct response of white and gray matters, the presence of different neurovascular structures, as well as due to the necrotic debris and hemorrhage in a tumor. Such heterogeneities might significantly complicate delineation of tumor margins during the intraoperative THz neurodiagnosis. The presented results for the first time pose the problem of studying the inhomogeneity of brain tissues that causes scattering of THz waves, as well as the urgent need to use the radiation transfer theory for describing the THz-wave - tissue interactions.

In situ terahertz monitoring of an ice ball formation during tissue cryosurgery: a feasibility test.

.Significance: Uncontrolled cryoablation of tissues is a strong reason limiting the wide application of cryosurgery and cryotherapy due to the certain risks of unpredicted damaging of healthy tissues. The existing guiding techniques are unable to be applied in situ or provide insufficient spatial resolution. Terahertz (THz) pulsed spectroscopy (TPS) based on sensitivity of THz time-domain signal to changes of tissue properties caused by freezing could form the basis of an instrument for observation of the ice ball formation.Aim: The ability of TPS for in situ monitoring of tissue freezing depth is studied experimentally.Approach: A THz pulsed spectrometer operated in reflection mode and equipped with a cooled sample holder and ex vivo samples of bovine visceral adipose tissue is applied. Signal spectrograms are used to analyze the changes of THz time-domain signals caused by the interface between frozen and unfrozen tissue parts.Results: Experimental observation of TPS signals reflected from freezing tissue demonstrates the feasibility of TPS to detect ice ball formation up to depth.Conclusions: TPS could become the promising instrument for in situ control of cryoablation, enabling observation of the freezing front propagation, which could find applications in various fields of oncology, regenerative medicine, and THz biophotonics.

Proof of concept for continuously-tunable terahertz bandpass filter based on a gradient metal-hole array.

A continuously-tunable terahertz (THz) bandpass filter based on the resonant electromagnetic-wave transmission through a metal-hole array featuring a gradually changing period was developed and fabricated on a silicon substrate using optical lithography. A gradient geometry of the metal-hole array yields a wide tunability of the filter transmission, when operating with a focussed THz beam. The filter was studied numerically, using the finite element method, and experimentally, using the THz pulsed spectroscopy. We find that the central wavelength of the filter transmission band can be tuned in the wide range of λc = 400-800 μm with the relative bandwidth of Δλ/λc ≃ ~0.4. Finally, Kapton-based anti-reflection coating was applied to the filter flat side, in order to suppress an interference pattern in the filter transmission spectrum. We believe that the developed filter holds strong potential for multispectral THz imaging and sensing due to its conceptual simplicity and case of operation. Moreover, the presented filter concept can be translated to other spectral ranges, where appropriate technologies are available for the fabrication of gradient sub-wavelength metal-hole arrays.

Using soy protein in the three-component phantom for breast cancer mimicking

Creation of the biological tissue phantoms especially breast tissue cancer in the terahertz frequency range is an actual problem of medical physics. This paper suggests using soy protein as one of the main component of breast tissue phantom instead of gelatin, as it’s water-and fat-holding substance, “quasi-bioidentical” to animal proteins and their chemical characteristics are stable in time. Implemented phantoms were analyzed experimentally by using terahertz pulsed spectroscopy, obtained results were compared with spectra of adipose, fibrous and cancer tissue (human female breast tissue).

Температурная эволюция диэлектрического отклика alpha-лактозы моногидрата в терагерцовом диапазоне частот

With a change in temperature, a-lactose monohydrate crystals undergo changes in the molecular structure due to dehydration and decay of intramolecular bonds. The transmission spectra of the pressed microcrystalline samples of a-lactose monohydrate were measured using terahertz pulsed spectroscopy in the temperature range of the existence of the solid phase 10 – 475 K. An analysis of the observed absorption lines using the classical oscillator model made it possible to reveal the complex temperature evolution of the eigenfreuencies of the resonances, as well as to determine the region of existence of response phase of a-lactose monohydrate. Data obtained can find practical application in various fields of terahertz optics, including pharmacology, food industry, analytical chemistry and biophotonics.

Terahertz Pulsed Spectroscopy for Optical and Dielectric Properties of Demineralized Bone Matrix, Collagen and Hydroxyapatite

Demineralized bone matrix (DBM) has osteoinductive potential functioning in many biological applications such as three-dimensional scaffold which assist new bone and cartilage growth by enhanced bioavailability of growth factors. Terahertz pulsed spectroscopy (TPS) was applied to investigate the optical and dielectric properties of camel femoral and cranial DBM, collagen type I, synthetic and natural hydroxyapatite powder (HA) in the range of 0.06-3.5THz. Terahertz (THz) absorption, refractive index (R.I) and dielectric properties (eʹ and eʺ) were found to be intensely differentiated to control and demineralized bone. Results presented the THz absorption fingerprint of all studied materials. The natural HA revealed higher R.I, eʹ, and eʺ values than both synthetic HA and collagen. Cranial DBM exhibited higher R.I compared to the control in all frequency ranges, whereas the femoral DBM behavior was frequency dependent. Demineralization produced significant increase in the values of eʹ and eʺ. THz dielectric properties acted as a sensitive predictor to the composition and microstructure of bone in different biological applications. Amalgamation of Infrared Spectroscopy and THz spectroscopy together with TGA, ICP and EDX can offer deep insight into the sample properties.

Study of blood and its components by terahertz pulsed spectroscopy

Study of blood and its components by terahertz pulsed spectroscopy

In vivo terahertz pulsed spectroscopy of dysplastic and non-dysplastic skin nevi

The results of the in vivo terahertz (THz) pulsed spectroscopy (TPS) of pigmentary skin nevi are reported. Observed THz dielectric permittivity of healthy skin and dysplastic and non-dysplastic skin nevi exhibits significant contrast in THz frequency range. Dysplastic skin nevus is a precursor of melanoma, which is reportedly the most dangerous cancer of the skin. Therefore, the THz dielectric spectroscopy is potentially an effective tool for non-invasive early diagnosis of melanomas of the skin.

Photoconductive devices for terahertz pulsed spectroscopy: a review [Invited

Photoconductive switches were the key components that allowed the generation and detection of coherent broadband electromagnetic pulses at terahertz frequencies, opening the possibility for performing spectroscopy and, therefore, measuring complex dielectric properties of materials in this band, which was mostly unexplored. In this paper, we present a brief introduction to the operation principles of these devices. Subsequently, we present a review of the current state-of-the-art in this field and discuss the challenges to be faced in future development of these devices.

Influence of Particle Size on Optical Constants From Pellets Measured With Terahertz Pulsed Spectroscopy

Particle size is shown to influence both the overall value and the measurement precision of the refractive index and absorption coefficient of a sample diluted with high density polyethylene (HDPE) powder and compressed in a pellet. However, excessive grinding of a sample before it is mixed with HDPE powder can result in the formation of large particle clusters. These aggregates can induce internal scattering of the terahertz pulse within the pellet as well as lead to different mechanical properties of the pellet, which may change the distribution of air pores. These phenomena result in extracted optical constants with low accuracy and precision. The present work introduces a simple experimental procedure to improve the precision and accuracy of optical constants from spectroscopic pellets. This procedure consists of moderately grinding the sample powder in fine HDPE powder with a pestle and mortar. The standard deviation of the refractive index of Prussian blue has been observed to reduce from 0.14 to 0.02 following this procedure.

A terahertz spectroscopic study of chitosan-based bionanocomposites containing clay nanoparticles

Dielectric properties of bionanocomposites resulting from regulated self-organization of chitosan and nanoparticles of synthetic saponite clay have been investigated by terahertz pulsed spectroscopy. Spectral characteristics of the composites considered in correlation with their structural features, which have been characterized by atomic force microscopy and scanning electron microscopy, depend on the concentration ratio of the components. The study of the effect of temperature on terahertz absorption spectra has led to the conclusion that hydrogen bonding may be involved in the formation of the bionanocomposites.

Non-Destructive Evaluation of Polymer Composite Materials at the Manufacturing Stage Using Terahertz Pulsed Spectroscopy

Nowadays, composite materials are widely used in building and construction industry, in motor-vehicles, spacecrafts and aircrafts, and in biomedical science due to the ability of combining various consistent components for manufacturing composite materials with physical and chemical properties significantly different from the properties of each component. Polymer composite materials (PCMs) appear to be the most common type of composites. PCMs consist mainly of polymer binder reinforced with the glass-fiber-fabric. Although PCMs are widely applied, PCM manufacturing technology lacks the methods of non- destructive testing. In this paper we demonstrate that terahertz (THz) pulsed spectroscopy (TPS) appears to be a unique instrument for solving important problems of PCM manufacturing control. We experimentally demonstrate the efficiency of TPS for non-destructive control of PCM binder polymerization, since THz radiation is sensitive to changes of picosecond dynamics in media. Furthermore, we show the ability to detect the internal non-impregnated voids inside the PCM structure by means of THz time-of-flight tomography. These results highlight the potentials of TPS applications for non-destructive control of PCM manufacturing process.

Terahertz spectroscopy of pigmentary skin nevi in vivo

Pigmentary skin nevi are studied in vivo using terahertz pulsed spectroscopy. Dielectric parameters of healthy skin and dysplastic and nondysplastic nevi are reconstructed and analyzed. The fact that complex permittivities of the samples substantially differ in the terahertz spectral range can be used for early noninvasive diagnostics of dysplastic nevi, which are precursors of melanoma (the most dangerous skin cancer). A method is proposed to identify various dysplastic and nondysplastic nevi using the analysis of terahertz dielectric characteristics. It is demonstrated that terahertz pulsed spectroscopy is promising for early noninvasive diagnostics of dysplastic nevi and melanomas of the skin.