In vivo estimation of water diffusivity in occluded human skin using terahertz reflection spectroscopy.

Water diffusion and the concentration profile within the skin significantly affect the surrounding chemical absorption and molecular synthesis. Occluding the skin causes water to accumulate in the top layer of the skin (the stratum corneum [SC]) and also affects the water diffusivity. Scar treatments such as silicone gel and silicone sheets make use of occlusion to increase skin hydration. However with existing techniques, it is not possible to quantitatively measure the diffusivity of the water during occlusion: current methods determine water diffusivity by measuring the water evaporated through the skin and thus require the skin to breathe. In this work, we use the high sensitivity of terahertz light to water to study how the water content in the SC changes upon occlusion. From our measurements, we can solve the diffusion equations in the SC to deduce the water concentration profile in occluded skin and subsequently to determine the diffusivity. To our knowledge, this is the first work showing how the diffusivity of human skin can be measured during occlusion and we envisage this paper as being used as a guide for non-invasively determining the diffusivity of occluded human skin in vivo.

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.

In vivo THz imaging of human skin: Accounting for occlusion effects.

In vivo terahertz (THz) imaging of human skin needs to be done in reflection geometry due to the high attenuation of THz light by water in the skin. To aid the measurement procedure, there is typically an imaging window onto which the patient places the area of interest. The window enables better pulse alignment and helps keep the patient correctly positioned during the measurement. In this paper, we demonstrate how the occlusion caused by the skin contact with the imaging window during the measurement affects the THz response. By studying both rapid point measurements and imaging over an area of a human volar forearm, we find that even 5 seconds of occlusion affects the THz response. As the occlusion time increases, the skin surface water content increases, resulting in the reduction of the amplitude of the reflected THz pulse, especially in the first 3 minutes. Furthermore, it was found that the refractive index of the volar forearm increased by 10% to 15% after 20 minutes of occlusion. In this work, we examine and propose a model for the occlusion effects due to the quartz window with a view to compensating for its influence.

Broadband modulation of terahertz waves through electrically driven hybrid bowtie antenna-VO2 devices.

Broadband modulation of terahertz (THz) light is experimentally realized through the electrically driven metal-insulator phase transition of vanadium dioxide (VO2) in hybrid metal antenna-VO2 devices. The devices consist of VO2 active layers and bowtie antenna arrays, such that the electrically driven phase transition can be realized by applying an external voltage between adjacent metal wires extended to a large area array. The modulation depth of the terahertz light can be initially enhanced by the metal wires on top of VO2 and then improved through the addition of specific bowties in between the wires. As a result, a terahertz wave with a large beam size (~10 mm) can be modulated within the measurable spectral range (0.3-2.5 THz) with a frequency independent modulation depth as high as 0.9, and the minimum amplitude transmission down to 0.06. Moreover, the electrical switch on/off phase transition depends very much on the size of the VO2 area, indicating that smaller VO2 regions lead to higher modulation speeds and lower phase transition voltages. With the capabilities in actively tuning the beam size, modulation depth, modulation bandwidth as well as the modulation speed of THz waves, our study paves the way in implementing multifunctional components for terahertz applications.

Determination of terahertz permittivity of dehydrated biological samples.

A key step in transforming terahertz imaging to a practical medical imaging modality lies in understanding the interactions between terahertz (THz) waves and biological tissues. Most of the models in the literature use the permittivity of liquid water to simulate the THz-tissue interactions, but they often neglect contributions from the biological background such as proteins and lipids because dehydrated biological samples are experimentally difficult to prepare. In this work, we present a method to prepare thin and flat dehydrated samples which can be easily handled and measured in a transmission setup. Our results will provide fundamental parameters for modelling THz-tissue interactions.

Recent advances in terahertz technology for biomedical applications.

Terahertz instrumentation has improved significantly in recent years such that THz imaging systems have become more affordable and easier to use. THz systems can now be operated by non-THz experts greatly facilitating research into many potential applications. Due to the non-ionising nature of THz light and its high sensitivity to soft tissues, there is an increasing interest in biomedical applications including both in vivo and ex vivo studies. Additionally, research continues into understanding the origin of contrast and how to interpret terahertz biomedical images. This short review highlights some of the recent work in these areas and suggests some future research directions.

In vivo terahertz reflection imaging of human scars during and after the healing process.

We use terahertz imaging to measure four human skin scars in vivo. Clear contrast between the refractive index of the scar and surrounding tissue was observed for all of the scars, despite some being difficult to see with the naked eye. Additionally, we monitored the healing process of a hypertrophic scar. We found that the contrast in the absorption coefficient became less prominent after a few months post-injury, but that the contrast in the refractive index was still significant even months post-injury. Our results demonstrate the capability of terahertz imaging to quantitatively measure subtle changes in skin properties and this may be useful for improving scar treatment and management.

Freeze-thaw hysteresis effects in terahertz imaging of biomedical tissues.

There have recently been several studies published involving terahertz (THz) imaging of frozen biomedical samples. In this paper, we investigate the effects of the freeze-thaw cycle on THz properties of porcine muscle and fat samples. For ordinary freezing, there was a significant change in the THz properties after thawing for muscle tissue but not for fat tissue. However, if snap-freezing was combined with fast-thawing instead of ordinary freezing and ordinary thawing, then the freeze-thaw hysteresis was removed.

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.

Gelatin embedding: a novel way to preserve biological samples for terahertz imaging and spectroscopy.

Sample dehydration has traditionally been a challenging problem in ex vivo terahertz biomedical experiments as water content changes significantly affect the terahertz properties and can diminish important contrast features. In this paper, we propose a novel method to prevent sample dehydration using gelatin embedding. By looking at terahertz image data and calculating the optical properties of the gelatin-embedded sample, we find that our method successfully preserves the sample for at least 35 h, both for imaging and spectroscopy. Our novel preservation method demonstrates for the first time the capability to simultaneously maintain sample structural integrity and prevent dehydration at room temperature. This is particularly relevant for terahertz studies of freshly excised tissues but could be beneficial for other imaging and spectroscopy techniques.

Terahertz time-domain and low-frequency Raman spectroscopy of organic materials.

With the ongoing proliferation of terahertz time-domain instrumentation from semiconductor physics into applied spectroscopy over the past decade, measurements at terahertz frequencies (1 THz ≡ 10(12) Hz ≡ 33 cm(-1)) have attracted a sustained growing interest, in particular the investigation of hydrogen-bonding interactions in organic materials. More recently, the availability of Raman spectrometers that are readily able to measure in the equivalent spectral region very close to the elastic scattering background has also grown significantly. This development has led to renewed efforts in performing spectroscopy at the interface between dielectric relaxation phenomena and vibrational spectroscopy. In this review, we briefly outline the underlying technology, the physical phenomena governing the light-matter interaction at terahertz frequencies, recent examples of spectroscopic studies, and the current state of the art in assigning spectral features to vibrational modes based on computational techniques.

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.

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.

Terahertz pulsed imaging in vivo: measurements and processing methods.

This paper presents a number of data processing algorithms developed to improve the accuracy of results derived from datasets acquired by a recently designed terahertz handheld probe. These techniques include a baseline subtraction algorithm and a number of algorithms to extract the sample impulse response: double Gaussian inverse filtering, frequency-wavelet domain deconvolution, and sparse deconvolution. In vivo measurements of human skin are used as examples, and a comparison is made of the terahertz impulse response from a number of different skin positions. The algorithms presented enables both the spectroscopic and time domain properties of samples measured in reflection geometry to be better determined compared to previous calculation methods.

Tuning the acid/base properties of nanocarbons by functionalization via amination.

The surface chemical properties and the electronic properties of vapor grown carbon nanofibers (VGCNFs) have been modified by treatment of the oxidized CNFs with NH(3). The effect of treatment temperature on the types of nitrogen functionalities introduced was evaluated by synchrotron based X-ray photoelectron spectroscopy (XPS), while the impact of the preparation methods on the surface acid-base properties was investigated by potentiometric titration, microcalorimetry, and zeta potential measurements. The impact of the N-functionalization on the electronic properties was measured by THz-Time Domain spectroscopy. The samples functionalized via amination are characterized by the coexistence of acidic and basic O and N sites. The population of O and N species is temperature dependent. In particular, at 873 K nitrogen is stabilized in substitutional positions within the graphitic structure, as heterocyclic-like moieties. The surface presents heterogeneously distributed and energetically different basic sites. A small amount of strong basic sites gives rise to a differential heat of CO(2) adsorption of 150 kJ mol(-1). However, when functionalization is carried out at 473 K, nitrogen moieties with basic character are introduced and the maximum heat of adsorption is significantly lower, at approximately 90 kJ mol(-1). In the latter sample, energetically different basic sites coexist with acidic oxygen groups introduced during the oxidative step. Under these conditions, a bifunctional acidic and basic surface is obtained with high hydrophilic character. N-functionalization carried out at higher temperature changes the electronic properties of the CNFs as evaluated by THz-TDS. The functionalization procedure presented in this work allows high versatility and flexibility in tailoring the surface chemistry of nanocarbon material to specific needs. This work shows the potential of the N-containing nanocarbon materials obtained via amination in catalysis as well as electronic device materials.

A study into the effect of subtle structural details and disorder on the terahertz spectrum of crystalline benzoic acid.

The phonon modes of crystalline benzoic acid have been investigated using terahertz time-domain spectroscopy, rigid molecule atom-atom model potential and plane-wave density functional theory lattice dynamics calculations. The simulation results show good agreement with the measured terahertz spectra and an assignment of the terahertz absorption features of benzoic acid is made with the help of both computational methods. Focussing on the strongest interactions in the crystal, we describe each vibration in terms of distortions of the benzoic acid hydrogen bonded dimers that are present in the crystal structure. The terahertz spectrum is also shown to be highly sensitive to the location of the carboxylic acid hydrogen atoms in the cyclic hydrogen-bonded dimers and we have systematically explored the influence of the observed disorder in the hydrogen atom positions on the lattice dynamics.