Optimized multilayer structure for sensitive THz characterization of thin-film glucose solutions.

Terahertz time-domain spectroscopy (THz-TDS) has shown promise in biomedical sample characterization and high characterization sensitivity is in demand due to the thin-film (TF) feature of the sample. This paper proposes an optimized multilayer structure for sensitive characterization of TF aqueous solutions in reflection THz-TDS. Theoretical simulations are conducted for structural optimization and the 75 µm window-sample-mirror structure displays the best sensitivity compared to other sandwich structures and traditional THz measurement geometries. 0-20% TF glucose solutions are then measured; and a spectral peak introduced by the proposed structure is observed to result in the high sensitivity. Our work provides a new way of customizing multilayer structure for THz thin-film characterization.

Simulated and Experimental Verification for a Terahertz Specific Finite Rate of Innovation Signal Processing Method.

Recently, finite rate of innovation methods have been successfully applied to achieve low sampling rates in many areas, such as for ultrasound and radio signals. However, to the best of our knowledge, there are no journal publications applying this to real terahertz signals. In this work, we mathematically describe a finite rate of innovation method applied specifically to terahertz signals both experimentally and in simulation. To demonstrate our method, we applied it to randomized simulated signals with and without the presence of noise and to simple experimental measurements. We found excellent agreement between the simulated signals and those recreated based on results from our method, with this success also being replicated experimentally. These results were obtained at relatively low sampling rates, compared to standard methods, which is a key advantage to using a finite rate of innovation method as it allows for faster data acquisition and signal processing.

Deep THz modulation at Fabry-Perot resonances using graphene in periodic microslits.

Potential applications of terahertz (THz) radiation are constantly being investigated for high-speed communication due to its large bandwidth. For example, frequency hopping communication technology would benefit from the large bandwidth. To attach the information to the carrier wave, THz modulators with deep and stable modulation at different frequencies are crucial, yet are still lacking. Here a THz modulator, designed by integrating a non-resonant field enhancement effect of periodic metal microslits to assist a Fabry-Perot resonance structure (MS-FP) is proposed and demonstrated. New equations are developed to describe the superior performance of the novel design. The >95% modulation depth is achieved by a SiO2/Si gated graphene device at 14 Fabry-Perot resonant frequencies across 1.4 THz bandwidth, outperforming the recently reported 75% modulation depth THz modulator with a similar Fabry-Perot structure.

THz Sensing of Human Skin: A Review of Skin Modeling Approaches.

The non-ionizing and non-invasive nature of THz radiation, combined with its high sensitivity to water, has made THz imaging and spectroscopy highly attractive for in vivo biomedical applications for many years. Among them, the skin is primarily investigated due to the short penetration depth of THz waves caused by the high attenuation by water in biological samples. However, a complete model of skin describing the THz-skin interaction is still needed. This is also fundamental to reveal the optical properties of the skin from the measured THz spectrum. It is crucial that the correct model is used, not just to ensure compatibility between different works, but more importantly to ensure the reliability of the data and conclusions. Therefore, in this review, we summarize the models applied to skin used in the THz regime, and we compare their adaptability, accuracy, and limitations. We show that most of the models attempt to extract the hydration profile inside the skin while there is also the anisotropic model that displays skin structural changes in the stratum corneum.

Broadband amplitude, frequency, and polarization splitter for terahertz frequencies using parallel-plate waveguide technology.

In this Letter, we report a broadband frequency/polarization demultiplexer based on parallel-plate waveguides (PPWGs) for terahertz (THz) frequencies. The fabrication and experimental validation of this polarization sensitive demultiplexer is demonstrated for the range from 0.2 to 1 THz. Upgrading the demultiplexer by adding a second demultiplexer stage, a fifty-fifty amplitude splitter is also demonstrated in the same frequency range. The multiplexer is based on a stainless-steel traveling-wave antenna, exhibiting strong mechanical robustness. This unique device exhibits three splitting mechanisms in the same device: amplitude, polarization, and frequency splitting. This is a significant improvement for the next generation of THz passive components for communication purposes.

Design and fabrication of 3-D printed conductive polymer structures for THz polarization control.

In this paper, we numerically and experimentally demonstrate the inverse polarization effect in three-dimensional (3-D) printed polarizers for the frequency range of 0.5 - 2.7 THz. The polarizers simply consist of 3-D printed strip lines of conductive polylactic acid (CPLA, Proto-Pasta) and do not require a substrate or any further metallic deposition. The experimental and numerical results show that the proposed structure acts as a broadband polarizer between the range of 0.3 THz to 2.7 THz, in which the inverse polarization effect is clearly seen for frequencies above 0.5 THz. In the inverse polarization effect, the transmission of the transverse electric (TE) component exceeds that of the TM component, in contrast to the behavior of a typical wire-grid polarizer. We show how the performance of the polarizers depends on the spacing and thickness of the CPLA structure; extinction ratios higher than 20 dB are achieved. This is the first report using CPLA to fabricate THz polarizers, demonstrating the potential of using conductive polymers to design THz components efficiently and robustly.

Utilizing multilayer structures to enhance terahertz characterization of thin films ranging from aqueous solutions to histology slides.

We propose a multilayer geometry to characterize thin-film samples in reflection terahertz time domain spectroscopy. Theory indicates that this geometry has higher sensitivity compared to ordinary transmission or reflection geometries when characterizing both low- and high-absorption samples. Pure water and water-ethanol mixtures are measured to verify the characterization accuracy of the proposed geometry and its capability to measure trace liquids. Paraffin-embedded oral cancer tissue is imaged to further show how the proposed geometry enhances the sensitivity for solid low-absorptive films.

A Sensitive and Versatile Thickness Determination Method Based on Non-Inflection Terahertz Property Fitting.

The accuracy of thin-film characterization in terahertz spectroscopy is mainly set by the thickness uncertainty. Physical thickness measurement has limited accuracy for thin-film samples thinner than a few hundreds of micrometers and is sometimes even impossible. The temporal resolution of time-domain terahertz spectrometers is not sufficient to resolve such thin films. Previously reported numerical methods mainly only work for materials with low dispersion and absorption. Here, we propose a novel method for thickness determination by fitting a non-inflection offset exponential function to the material optical properties. Theoretical analysis predicts the best fitting to only be achieved when the correct thickness is given. Transmission measurements on a thin-film polymer, water, and a lactose pallet verify the theory and show the accurate thickness determination and property characterization on materials which are either achromatic or dispersive, transparent or absorptive, featureless or resonant. The measurements demonstrate the best versatility and sensitivity compared to the state-of-art. The method could be widely adapted to various types of research and industrial applications.

Three dimensional chiral plasmon rulers based on silver nanorod trimers.

The symmetry dependences of plasmon excitation modes are studied in 3D silver nanorod trimers. The degenerate plasmon modes split into chiral modes by breaking the inversion and mirror symmetry of the nanorod trimer through translation and/or rotation of the middle rod. With a translation operation, successive evolution of the circular dichroism (CD) spectrum can be achieved through gradual breaking of the inversion symmetry. An additional rotation operation produces even dramatic spectral changes due to breaking a quasi-mirror symmetry resulted from the same angular distance of the middle rod to the top and bottom rods. Especially, pairs of new chiral modes can be excited due to the contact of the middle rod with the top-bottom rod pair. The spectral changes in the simulations, which are also demonstrated experimentally, envision the 3D chiral nanorod trimer system as plasmon ruler for spatial configuration retrieval and dynamic bio-process analysis at the single molecule level.

Composite multiscale entropy analysis of reflective terahertz signals for biological tissues.

We demonstrate a composite multiscale entropy (CMSE) method of terahertz (THz) signal complexity analysis to distinguish different biological tissues. The THz signals reflected from fresh porcine skin and muscle tissues were measured and analyzed. The statistically significant difference and separation of the two tissues based on several parameters were analyzed and compared for THz spectroscopy and imaging, which verified the better performance of the CMSE method and further enhancement of the contrast among THz signals that interact with different tissues. This process provides a better analysis and discrimination method for THz spectroscopy and imaging in biomedical applications.

Vanadium dioxide devices for terahertz wave modulation: a study of wire grid structures.

Vandium dioxide (VO2) shows promise as the basis for a terahertz wave modulator due to its phase transition properties. Its insulator-metal-transition (IMT) can be induced either through temperature changes, optically or electronically. Recently, a metal-VO2 wire grid structure was proposed which was able to increase the modulation depth (MD) from 0.65 to 0.9, suggesting that these simple metallic structures could greatly increase the difference in terahertz transmission for the insulating and metallic states of VO2 based structures. In this paper, we have found that the increase in MD decreases with increasing VO2 conductivity in the metallic state, resulting in a maximum modulation depth of approximately 0.95 for wire grid structures that preserves a high transmission in the insulating state. Surprisingly, we find that deposition of VO2 on top of metallic structures results in reduced performance. However, we find that devices based upon VO2 alone can achieve unexpectedly high performance. In this work we present a device with a switchable wire-grid polariser effect over a broadband frequency range (from 0.3 to 2 THz). To our knowledge this is the first such broadband metamaterial based solely on VO2. The ability to switch on a metamaterial property like this to produce a polarisation effect is very useful for future terahertz optical devices such as rotators and waveplates.

Low-cost and broadband terahertz antireflection coatings based on DMSO-doped PEDOT/PSS.

We report the potential application of 6% dimethylsulfoxide (DMSO)-doped poly (3, 4-ethylenedioxythiophene)/poly (4-styrenesulfonate) (PEDOT/PSS) as a low cost and broadband terahertz (THz) antireflection coating based on the impedance matching effect. The reflected pulses from the quartz and silicon substrates are observed to change with the thickness of the PEDOT/PSS layer. Theoretical analysis based on an equivalent transmission line circuit model and FDTD computational simulations have been used to understand the experimental results. Excellent impedance matching is achieved by a ∼39-nm-thick 6% DMSO-doped PEDOT/PSS layer on quartz, and a ∼101-nm-thick 6% DMSO-doped PEDOT/PSS layer on silicon due to the almost-frequency-independent conductivity of the thin film between 0.3 and 2.5 THz. In the critical conditions, the normalized main pulse transmission remains as high as 74% and 64%, for the quartz and silicon substrates, respectively, significantly higher than the existing state of the art THz antireflection coatings.

High extinction ratio and low transmission loss thin-film terahertz polarizer with a tunable bilayer metal wire-grid structure.

A thin-film terahertz polarizer is proposed and realized via a tunable bilayer metal wire-grid structure to achieve high extinction ratios and good transmission. The polarizer is fabricated on top of a thin silica layer by standard micro-fabrication techniques to eliminate the multireflection effects. The tunable alignment of the bilayer aluminum-wire grid structure enables tailoring of the extinction ratio and transmission characteristics. Using terahertz time-domain spectroscopy (THz-TDS), a fabricated polarizer is characterized, with extinction ratios greater than 50 dB and transmission losses below 1 dB reported in the 0.2-1.1 THz frequency range. These characteristics can be improved by further tuning the polarizer parameters such as the pitch, metal film thickness, and lateral displacement.

Automatic online detection of atrial fibrillation based on symbolic dynamics and Shannon entropy.

BACKGROUND: Atrial fibrillation (AF) is the most common and debilitating abnormalities of the arrhythmias worldwide, with a major impact on morbidity and mortality. The detection of AF becomes crucial in preventing both acute and chronic cardiac rhythm disorders. OBJECTIVE: Our objective is to devise a method for real-time, automated detection of AF episodes in electrocardiograms (ECGs). This method utilizes RR intervals, and it involves several basic operations of nonlinear/linear integer filters, symbolic dynamics and the calculation of Shannon entropy. Using novel recursive algorithms, online analytical processing of this method can be achieved. RESULTS: Four publicly-accessible sets of clinical data (Long-Term AF, MIT-BIH AF, MIT-BIH Arrhythmia, and MIT-BIH Normal Sinus Rhythm Databases) were selected for investigation. The first database is used as a training set; in accordance with the receiver operating characteristic (ROC) curve, the best performance using this method was achieved at the discrimination threshold of 0.353: the sensitivity (Se), specificity (Sp), positive predictive value (PPV) and overall accuracy (ACC) were 96.72%, 95.07%, 96.61% and 96.05%, respectively. The other three databases are used as testing sets. Using the obtained threshold value (i.e., 0.353), for the second set, the obtained parameters were 96.89%, 98.25%, 97.62% and 97.67%, respectively; for the third database, these parameters were 97.33%, 90.78%, 55.29% and 91.46%, respectively; finally, for the fourth set, the Sp was 98.28%. The existing methods were also employed for comparison. CONCLUSIONS: Overall, in contrast to the other available techniques, the test results indicate that the newly developed approach outperforms traditional methods using these databases under assessed various experimental situations, and suggest our technique could be of practical use for clinicians in the future.

Effect of transdermal drug delivery patches on the stratum corneum: in vivo inspection with a handheld terahertz probe.

Transdermal drug delivery patches are a good alternative to hypodermic drug injection. The drug delivery efficiency depends strongly on the hydration of the skin under treatment, and therefore, it is essential to study the effects on the skin induced by the application of these medical-grade patches. Terahertz (THz) spectroscopy shows great promise for non-invasive skin evaluation due to its high sensitivity to subtle changes in water content, low power and non-ionizing properties. In this work, we study the effects of transdermal drug delivery patches (three fully occlusive and three partially occlusive) applied on the upper arms of ten volunteers for a maximum period of 28 h. Three different levels of propylene glycol (0 %, 3 % and 6 %) are added to the patches as excipient. By performing multilayer analysis, we successfully retrieve the water content of the stratum corneum (SC) which is the outermost layer of skin, as well as its thickness at different times before and after applying the patches. This study demonstrates the potential of using THz sensing for non invasive skin monitoring and has wide applications for skin evaluation as well as the development of skin products.

Quantitative evaluation of transdermal drug delivery patches on human skin with in vivo THz-TDS.

Transdermal drug delivery (TDD) has been widely used in medical treatments due to various advantages, including delivering drugs at a consistent rate. However, variations in skin hydration can have a significant effect on the permeability of chemicals. Therefore, it is essential to study the changes in skin hydration induced by TDD patches for better control of the delivery rate. In this work, in vivo terahertz (THz) spectroscopy is conducted to quantitatively monitor human skin after the application of patches with different backing materials and propylene glycol concentrations. Changes in skin hydration and skin response to occlusion induced by other patches are investigated and compared. Our work demonstrates the potential application of in vivo THz measurements in label-free, non-invasive evaluation of transdermal patches on human skin and further reveals the mechanism behind the effect.

Spectroscopic insight on impact of environment on natural photoprotectants.

Biomimicry has become a key player in researching new materials for a whole range of applications. In this study, we have taken a crude extract from the red algae Palmaria palmata containing mycosporine-like amino acids - a photoprotective family of molecules. We have applied the crude extract onto a surface to assess if photoprotection, and more broadly, light-to-heat conversion, is retained; we found it is. Considering sunscreens as a specific application, we have performed transmission and reflection terahertz spectroscopy of the extract and glycerol to demonstrate how one can monitor stability in real-world applications.

Evaluating liquid crystal properties for use in terahertz devices.

Despite the wide application of liquid crystals (LCs) in the visible frequency range, their properties in the terahertz range have not yet been extensively investigated. In this paper we have investigated the terahertz properties of LCs E7, BL037, RDP-94990 and RDP-97304 using terahertz time-domain-spectroscopy. We find that RDP-94990 has the largest birefringence and smallest absorption in the terahertz range compared to E7 and BL037. We highlight the importance of investigating all parameters, not just the birefringence, when designing fast, efficient and transmissive terahertz LC devices.

Investigating antibody interactions with a polar liquid using terahertz pulsed spectroscopy.

In this article, we use terahertz spectroscopy to study the dielectric properties of the peroxidase-conjugated affinity purified goat anti-cat immunoglobulin G and the fluorescein-conjugated affinity purified goat anti-cat immunoglobulin G when they interact with polar liquids. The influence of protein concentration, as well as presence of glycerol as a cosolvent, is determined by estimation of the effective hydration shell radius of the protein in solution. The dielectric spectra in this study are measured over the frequency range 0.1-1.3 THz and it is found that the dielectric properties are dependent on the type of the charges in the hydrogen-bonded antibodies' networks. Our results indicate that the terahertz dielectric properties of polar liquids are strongly affected by the presence of the antibody and suggest that the dielectric spectrum is particularly powerful in the study of structural and conformational properties of proteins. Therefore, terahertz spectroscopy is a very sensitive approach to investigate structural features of biological systems.

The effects of pre-ejection period on post-exercise systolic blood pressure estimation using the pulse arrival time technique.

Pulse arrival time (PAT) is comprised of the vascular transit time (TT) through the arterial system and the pre-ejection period (PEP) in the heart. It has been used to predict arterial blood pressure (BP) without using a cuff. The aim of this study was to investigate the effects of including the PEP on the accuracy of cuffless systolic BP (SBP) estimation using the PAT technique in post-exercise recovery. Experiments were conducted on 22 normotensive participants. PAT, TT and PEP were determined from simultaneous measurements of the electrocardiogram, photoplethysmogram and impedance cardiogram. Moderate exercise induced significant (p < 0.05) increases in SBP and heart rate and significant (p < 0.05) decreases in PEP and PAT. Diastolic blood pressure and TT only varied insignificantly (p > 0.05). SBP was moderately correlated with PEP (r = -0.61) and PAT (r = -0.81). PAT and PEP were moderately correlated (r = 0.67). When SBP was estimated using least-squares methods, the differences between the measured and predicted SBP using PEP, PAT and TT were 0.0 ± 6.6, 0.0 ± 4.9 and 0.0 ± 9.3 mmHg, respectively. The findings suggested that PAT gives the best SBP prediction and PEP has some potential to predict blood pressure. The inclusion of PEP in the PAT measurement is necessary to facilitate accurate cuffless blood pressure prediction after exercise.