Split ring multiband refractive index cancer sensor based on terahertz radiation.

A design of a multiband terahertz (THz) metamaterial biosensor for early cancer detection is proposed. The THz biosensor composed of several arc-shaped connecting parts operates at three different frequencies, and the absorptivity of the three resonant frequencies exceeds 99% in free space. In this work, we analyzed the absorption spectrum and polarization independence under different design parameters, improved the performance of the sensor by adjusting the absorption characteristics of the sensor, and gave the calculation results. Additionally, we studied the influence of the refractive index and thickness of different samples on the sensor, and theoretically calculated the sensitivity of the sensor to basal cells, breast cells, cervical cells, and their corresponding cancer cells. The result shows that the maximum sensitivity of the sensor can reach 642.5 GHz/RIU, which is much higher than the reported biosensors. Therefore, the proposed THz sensor has great potential in early detection and early warning of cancer.

Calcium Imaging Characterize the Neurobiological Effect of Terahertz Radiation in Zebrafish Larvae.

(1) Objective: To explore the neurobiological effects of terahertz (THz) radiation on zebrafish larvae using calcium (Ca2+) imaging technology. (2) Methods: Zebrafish larvae at 7 days post fertilization (dpf) were exposed to THz radiation for 10 or 20 min; the frequency was 2.52 THz and the amplitude 50 mW/cm2. The behavioral experiments, neural Ca2+ imaging, and quantitative polymerase chain reaction (qPCR) of the dopamine-related genes were conducted following the irradiation. (3) Results: Compared with the control group, the behavioral experiments demonstrated that THz radiation significantly increased the distance travelled and speed of zebrafish larvae. In addition, the maximum acceleration and motion frequency were elevated in the 20 min radiation group. The neural Ca2+ imaging results indicated a substantial increase in zebrafish neuronal activity. qPCR experiments revealed a significant upregulation of dopamine-related genes, such as drd2b, drd4a, slc6a3 and th. (4) Conclusion: THz radiation (2.52 THz, 50 mW/cm2, 20 min) upregulated dopamine-related genes and significantly enhanced neuronal excitability, and the neurobiological effect of THz radiation can be visualized using neural Ca2+ imaging in vivo.

The Microscopic Mechanisms of Nonlinear Rectification on Si-MOSFETs Terahertz Detector.

Studying the nonlinear photoresponse of different materials, including III-V semiconductors, two-dimensional materials and many others, is attracting burgeoning interest in the terahertz (THz) field. Especially, developing field-effect transistor (FET)-based THz detectors with preferred nonlinear plasma-wave mechanisms in terms of high sensitivity, compactness and low cost is a high priority for advancing performance imaging or communication systems in daily life. However, as THz detectors continue to shrink in size, the impact of the hot-electron effect on device performance is impossible to ignore, and the physical process of THz conversion remains elusive. To reveal the underlying microscopic mechanisms, we have implemented drift-diffusion/hydrodynamic models via a self-consistent finite-element solution to understand the dynamics of carriers at the channel and the device structure dependence. By considering the hot-electron effect and doping dependence in our model, the competitive behavior between the nonlinear rectification and hot electron-induced photothermoelectric effect is clearly presented, and it is found that the optimized source doping concentrations can be utilized to reduce the hot-electron effect on the devices. Our results not only provide guidance for further device optimization but can also be extended to other novel electronic systems for studying THz nonlinear rectification.

The Effects of mmW and THz Radiation on Dry Eyes: A Finite-Difference Time-Domain (FDTD) Computational Simulation Using XFdtd.

The importance of investigating the health effects of RF radiation on the cornea cannot be overstated. This study aimed to address this need by utilizing a mathematical simulation to examine the absorption of millimeter wave (mmW) and terahertz (THz) waves by the cornea, considering both normal and pathological conditions. The simulation incorporated variations in tear film thickness and hydration levels, as these factors play a crucial role in corneal health. To assess the impact of RF radiation on the cornea, the study calculated temperature rises, which indicate heating effects for both dry and normal eyes. XFdtd, a widely used commercial software based on the Finite-Difference Time Domain (FDTD) method, was employed to evaluate the radiation absorption and resulting temperature changes. The outcomes of this study demonstrated a crucial finding, i.e., that changes in the water ratio and thickness of the tear film, which are associated with an increased risk of dry eye syndrome, directly impact the absorption of mmW and THz waves by the cornea. This insight provides valuable evidence supporting the interconnection between tear film properties and the vulnerability of the cornea to RF radiation.

Terahertz Detectors Using Microelectromechanical System Resonators.

The doubly clamped microelectromechanical system (MEMS) beam resonators exhibit extremely high sensitivity to tiny changes in the resonance frequency owing to their high quality (Q-) factors, even at room temperature. Such a sensitive frequency-shift scheme is very attractive for fast and highly sensitive terahertz (THz) detection. The MEMS resonator absorbs THz radiation and induces a temperature rise, leading to a shift in its resonance frequency. This frequency shift is proportional to the amount of THz radiation absorbed by the resonator and can be detected and quantified, thereby allowing the THz radiation to be measured. In this review, we present an overview of the THz bolometer based on the doubly clamped MEMS beam resonators in the aspects of working principle, readout, detection speed, sensitivity, and attempts at improving the performance. This allows one to have a comprehensive view of such a novel THz detector.

High-power two-color plasma-based THz generation driven by a Tm-doped fiber laser.

We report on the efficient generation of broadband THz radiation based on a two-color gas-plasma scheme. Broadband THz pulses covering the whole THz spectral region, from 0.1-35 THz, are generated. This is enabled by a high-power, ultra-fast, thulium-doped, fiber chirped pulse amplification (Tm:FCPA) system and a subsequent nonlinear pulse compression stage that uses a gas-filled capillary. The driving source delivers 40 fs pulses at a central wavelength of 1.9 µm with 1.2 mJ pulse energy and 101 kHz repetition rate. Owing to the long driving wavelength and the use of a gas-jet in the THz generation focus, the highest reported conversion efficiency for high-power THz sources (>20 mW) of 0.32% has been achieved. The high efficiency and average power of 380 mW of the broadband THz radiation make this an ideal source for nonlinear, tabletop THz science.

Observation of conical emission from DC-biased filament at 10 THz.

The terahertz (THz) radiation emitted by an air-based femtosecond filament biased by a static electric field is known to have on-axis shape and relatively low frequency spectrum in contrast to the unbiased single-color and two-color schemes. Here, we measure the THz emission of a 15-kV/cm-biased filament in air produced by a 740-nm, 1.8-mJ, 90-fs pulse and demonstrate that a flat-top on-axis THz angular distribution of the emission at 0.5-1 THz transforms into a contrast ring-shaped one at 10 THz.

Generation of sub-MV/cm terahertz fields with large-size Cherenkov-type optical-to-terahertz converters.

It is known that a structure comprising a tens of microns thick, and ∼1 × 1 cm2 in size, layer of LiNbO3 attached to a Si prism can serve as an efficient Cherenkov-type converter of tens of microjoules-energy femtosecond laser pulses to broadband terahertz radiation. Here we experimentally demonstrate scaling up the terahertz energy and field strength by extending the width of the converter to several centimeters, expanding appropriately the pump laser beam, and increasing the pump pulse energy to hundreds of microjoules. In particular, chirped Ti:sapphire laser pulses of 450 fs duration and 600 µJ energy were converted to 1.2 µJ terahertz pulses, and 0.5 MV/cm peak terahertz field was obtained when pumping by unchirped laser pulses of 60 fs duration and 200 µJ energy.

Observation of Magnetic State Dependent Thermoelectricity in Superconducting Spin Valves.

Superconductor-ferromagnet tunnel junctions demonstrate giant thermoelectric effects that are being exploited to engineer ultrasensitive terahertz radiation detectors. Here, we experimentally observe the recently predicted complete magnetic control over thermoelectric effects in a superconducting spin valve, including the dependence of its sign on the magnetic state of the spin valve. The description of the experimental results is improved by the introduction of an interfacial domain wall in the spin filter layer interfacing the superconductor. Surprisingly, the application of high in-plane magnetic fields induces a double sign inversion of the thermoelectric effect, which exhibits large values even at applied fields twice the superconducting critical field.

Translocation and fate of nanospheres in pheochromocytoma cells following exposure to synchrotron-sourced terahertz radiation.

The routes by which foreign objects enter cells is well studied; however, their fate following uptake has not been explored extensively. Following exposure to synchrotron-sourced (SS) terahertz (THz) radiation, reversible membrane permeability has been demonstrated in eukaryotic cells by the uptake of nanospheres; nonetheless, cellular localization of the nanospheres remained unclear. This study utilized silica core-shell gold nanospheres (AuSi NS) of diameter 50 ± 5 nm to investigate the fate of nanospheres inside pheochromocytoma (PC 12) cells following SS THz exposure. Fluorescence microscopy was used to confirm nanosphere internalization following 10 min of SS THz exposure in the range 0.5-20 THz. Transmission electron microscopy followed by scanning transmission electron microscopy energy-dispersive spectroscopic (STEM-EDS) analysis was used to confirm the presence of AuSi NS in the cytoplasm or membrane, as single NS or in clusters (22% and 52%, respectively), with the remainder (26%) sequestered in vacuoles. Cellular uptake of NS in response to SS THz radiation could have suitable applications in a vast number of biomedical applications, regenerative medicine, vaccines, cancer therapy, gene and drug delivery.

Sensitivity of Neuroblastoma and Induced Neural Progenitor Cells to High-Intensity THz Radiation.

THz radiation induces a variety of processes in cells and has attracted the attention of researchers in recent decades. Here, data on the effects of high-intensity terahertz (THz) radiation on human directly reprogrammed neural progenitor cells (drNPCs) and on neuroblastoma cells (SK-N-BE (2)) were obtained for the first time. The results demonstrated that the exposure of non-tumor and tumor cells to broadband (0.1-3 THz) THz pulses with the intensity of 21 GW/cm2 and the electric field strength of 2.8 MV/cm for 30 min induced neither a noticeable genotoxic effect nor a statistically significant change in the proliferative activity and cell differentiation. It was also shown that the combined effect of THz radiation and salinomycin, a promising antitumor agent, on neuroblastoma cells did not enhance the genotoxic effect of this antibiotic. However, further studies involving chemotherapy drugs and other exposure parameters are warranted to introduce this new concept into anti-tumor clinical practice and to enhance the efficacy of the existing approaches.

Epigenetic modification of gene expression in cancer cells by terahertz demethylation.

Terahertz (THz) radiation can affect the degree of DNA methylation, the spectral characteristics of which exist in the terahertz region. DNA methylation is an epigenetic modification in which a methyl (CH3) group is attached to cytosine, a nucleobase in human DNA. Appropriately controlled DNA methylation leads to proper regulation of gene expression. However, abnormal gene expression that departs from controlled genetic transcription through aberrant DNA methylation may occur in cancer or other diseases. In this study, we demonstrate the modification of gene expression in cells by THz demethylation using resonant THz radiation. Using an enzyme-linked immunosorbent assay, we observed changes in the degree of global DNA methylation in the SK-MEL-3 melanoma cell line under irradiation with 1.6-THz radiation with limited spectral bandwidth. Resonant THz radiation demethylated living melanoma cells by 19%, with no significant occurrence of apurinic/apyrimidinic sites, and the demethylation ratio was linearly proportional to the power of THz radiation. THz demethylation downregulates FOS, JUN, and CXCL8 genes, which are involved in cancer and apoptosis pathways. Our results show that THz demethylation has the potential to be a gene expression modifier with promising applications in cancer treatment.

Effects of Terahertz Radiation on the Aggregation of Alzheimer's Aß42 Peptide.

The pathophysiology of Alzheimer's disease is thought to be directly linked to the abnormal aggregation of ß-amyloid (Aß) in the nervous system as a common neurodegenerative disease. Consequently, researchers in many areas are actively looking for factors that affect Aß aggregation. Numerous investigations have demonstrated that, in addition to chemical induction of Aß aggregation, electromagnetic radiation may also affect Aß aggregation. Terahertz waves are an emerging form of non-ionizing radiation that has the potential to affect the secondary bonding networks of biological systems, which in turn could affect the course of biochemical reactions by altering the conformation of biological macromolecules. As the primary radiation target in this investigation, the in vitro modeled Aß42 aggregation system was examined using fluorescence spectrophotometry, supplemented by cellular simulations and transmission electron microscopy, to see how it responded to 3.1 THz radiation in various aggregation phases. The results demonstrated that in the nucleation aggregation stage, 3.1 THz electromagnetic waves promote Aß42 monomer aggregation and that this promoting effect gradually diminishes with the exacerbation of the degree of aggregation. However, by the stage of oligomer aggregation into the original fiber, 3.1 THz electromagnetic waves exhibited an inhibitory effect. This leads us to the conclusion that terahertz radiation has an impact on the stability of the Aß42 secondary structure, which in turn affects how Aß42 molecules are recognized during the aggregation process and causes a seemingly aberrant biochemical response. Molecular dynamics simulation was employed to support the theory based on the aforementioned experimental observations and inferences.

Enhanced in-situ liquid transport investigation setup for pharmaceutical tablet disintegration analysis using terahertz radiation.

The disintegration process of pharmaceutical solid dosage forms commences on contact with the dissolution medium and continues with subsequent spontaneous imbibition of the medium in the tablet matrix. Identifying the location of the liquid front in situ during imbibition, therefore, plays a significant role in understanding and modelling the disintegration process. Terahertz pulsed imaging (TPI) technology can be used to investigate this process by its ability to penetrate and identify the liquid front in pharmaceutical tablets. However, previous studies were limited to samples suitable for a flow cell environment, i.e. flat cylindrical disk shapes; thus, most commercial tablets could only be measured with prior destructive sample preparation. This study presents a new experimental setup named open immersion to measure a wide range of pharmaceutical tablets in their intact form. Besides, a series of data processing techniques to extract subtle features of the advancing liquid front are designed and utilised, effectively increasing the maximum thickness of tablets that can be analysed. We used the new method and successfully measured the liquid ingress profiles for a set of oval convex tablets prepared from a complex eroding immediate-release formulation.

Biological responses to terahertz radiation with different power density in primary hippocampal neurons.

Terahertz (THz) radiation is a valuable imaging and sensing tool which is widely used in industry and medicine. However, it biological effects including genotoxicity and cytotoxicity are lacking of research, particularly on the nervous system. In this study, we investigated how terahertz radiation with 10mW (0.12 THz) and 50 mW (0.157 THz) would affect the morphology, cell growth and function of rat hippocampal neurons in vitro.

Studying the genotoxic effects of high intensity terahertz radiation on fibroblasts and CNS tumor cells.

The data is obtained on the effect of high-intensity pulses of terahertz (THz) radiation with a broad spectrum (0.2-3 THz) on cell cultures. We have evaluated the threshold exposure parameters of THz radiation causing genotoxic effects in fibroblasts. Phosphorylation of histone H2AX at Ser 139 (γH2AX) was chosen as a marker for genotoxicity and a quantitative estimation of γH2AX foci number in fibroblasts was performed after cell irradiation with THz pulses for 30 min. No genotoxic effects of THz radiation were observed in fibroblasts unless peak intensity and electric field strength exceeded 21 GW cm-2 and 2.8 MV cm-1 , respectively. In tumor cell lines (neuroblastoma (SK-N-BE (2)) and glioblastoma (U87)), exposure to THz pulses with peak intensity of 21 GW cm-2 for 30 min caused no morphological changes as well as no statistically significant increase in histone phosphorylation foci number.

Electro-Optical Sampling of Single-Cycle THz Fields with Single-Photon Detectors.

Electro-optical sampling of Terahertz fields with ultrashort pulsed probes is a well-established approach for directly measuring the electric field of THz radiation. This technique usually relies on balanced detection to record the optical phase shift brought by THz-induced birefringence. The sensitivity of electro-optical sampling is, therefore, limited by the shot noise of the probe pulse, and improvements could be achieved using quantum metrology approaches using, e.g., NOON states for Heisenberg-limited phase estimation. We report on our experiments on THz electro-optical sampling using single-photon detectors and a weak squeezed vacuum field as the optical probe. Our approach achieves field sensitivity limited by the probe state statistical properties using phase-locked single-photon detectors and paves the way for further studies targeting quantum-enhanced THz sensing.

Specific Features of the Proteomic Response of Thermophilic Bacterium Geobacillus icigianus to Terahertz Irradiation.

Studying the effects of terahertz (THz) radiation on the proteome of temperature-sensitive organisms is limited by a number of significant technical difficulties, one of which is maintaining an optimal temperature range to avoid thermal shock as much as possible. In the case of extremophilic species with an increased temperature tolerance, it is easier to isolate the effects of THz radiation directly. We studied the proteomic response to terahertz radiation of the thermophilic Geobacillus icigianus, persisting under wide temperature fluctuations with a 60 °C optimum. The experiments were performed with a terahertz free-electron laser (FEL) from the Siberian Center for Synchrotron and Terahertz Radiation, designed and employed by the Institute of Nuclear Physics of the SB of the RAS. A G. icigianus culture in LB medium was THz-irradiated for 15 min with 0.23 W/cm2 and 130 µm, using a specially designed cuvette. The life cycle of this bacterium proceeds under conditions of wide temperature and osmotic fluctuations, which makes its enzyme systems stress-resistant. The expression of several proteins was shown to change immediately after fifteen minutes of irradiation and after ten minutes of incubation at the end of exposure. The metabolic systems of electron transport, regulation of transcription and translation, cell growth and chemotaxis, synthesis of peptidoglycan, riboflavin, NADH, FAD and pyridoxal phosphate cofactors, Krebs cycle, ATP synthesis, chaperone and protease activity, and DNA repair, including methylated DNA, take part in the fast response to THz radiation. When the response developed after incubation, the systems of the cell's anti-stress defense, chemotaxis, and, partially, cell growth were restored, but the respiration and energy metabolism, biosynthesis of riboflavin, cofactors, peptidoglycan, and translation system components remained affected and the amino acid metabolism system was involved.

Investigating the Impact of Synchrotron THz Radiation on the Corneal Hydration Using Synchrotron THz-Far Infrared Beamline.

Due to increasing interest in imaging, industrial, and the development of wireless communication operating at THz frequencies, it is crucial to ascertain possible health impacts arising from exposure to THz radiation. This paper reports on the pilot study of transmittance and absorbance spectra of the porcine cornea following THz frequency irradiation at a synchrotron THz/Far-IR beamline. The exposure period was 4 hours. One cornea was exposed to the radiation, with a second cornea acting as a control. An Attenuated Total Reflection (ATR) apparatus was used, and the frequency range of 2.4 to 8 THz was selected to evaluate any changes. It was found that the synchrotron THz radiation intensities are too low to produce induced corneal injury, but may lead to subtle changes in the state of water. Our results suggest that THz spectroscopy is a promising modality for corneal tissue hydration sensing.

Frequency down-conversion based on optical cascading process-New effective way for generation of far infrared or THz radiation.

Infrared and THz optics has many promising practical applications such as in spectroscopy, diagnostic, optical metrology, sensing, and many others. Due to limited number of IR radiation sources, the frequency down-conversion processes are widely used for obtaining infrared radiation. Among them, the most applicable method is a generation of wave with difference frequency under the three-waves interaction in a medium with quadratic nonlinear response. Below we propose a new effective tool for three times decreasing frequency of the incident pulse based on three-waves interaction in a medium with the quadratic susceptibility. At such interaction, a medium's response inherent cubic non-linearity appears due to so-called cascading SHG. The frequency down-conversion process possesses two stable modes. This is shown using multi-scale method. For each of the modes, the analytical solution is developed in the framework of the long pulse duration approximation without using the pump energy non-depletion approximation. The computer simulation results confirm those of analytical analysis. We show that the conversion efficiency of the incidentpump pulse energy achieves about 70%, if the low frequency wave incident intensity equals zero, or almost 100%, if the incident intensity of the low frequency wave is non-zero. The developed theoretical approach may be applied to other processes of the frequency down-conversion.