X. Chen, H. Lindley-Hatcher, R. I. Stantchev, J. Wang, K. Li, A. I. Hernandez-Serrano, Z. D. Taylor, E. Castro-Camus and E. Pickwell-MacPherson Chem. Phys. Rev. 3, 011311 (June 2022)
Terahertz (THz) technology has experienced rapid development in the past two decades. Growing numbers of interdisciplinary applications are emerging, including materials science, physics, communications, and security as well as biomedicine. THz biophotonics involves studies applying THz photonic technology in biomedicine, which has attracted attention due to the unique features of THz waves, such as the high sensitivity to water, resonance with biomolecules, favorable spatial resolution, capacity to probe the water–biomolecule interactions, and nonionizing photon energy. Despite the great potential, THz biophotonics is still at an early stage of development. There is a lack of standards for instrumentation, measurement protocols, and data analysis, which makes it difficult to make comparisons among all the work published. In this article, we give a comprehensive review of the key findings that have underpinned research into biomedical applications of THz technology. In particular, we will focus on the advances made in general THz instrumentation and specific THz-based instruments for biomedical applications. We will also discuss the theories describing the interaction between THz light and biomedical samples. We aim to provide an overview of both basic biomedical research as well as pre-clinical and clinical applications under investigation. The paper aims to provide a clear picture of the achievements, challenges, and future perspectives of THz biophotonics.
X. Ding, A. I. Hernandez-Serrano, H. Lindley-Hatcher, R. I. Stantchev, J. Zhou and E. Pickwell-MacPherson Optics Express 30, 18079 (May 2022)
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.
X. E. Ramirez Barker, R. I. Stantchev, A. I. Hernandez-Serrano and E. Pickwell-MacPherson Sensors 22, 3387 (April 2022)
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.
H. Lindley-Hatcher, R. I. Stantchev, X. Chen, A. I. Hernandez-Serrano, J. Hardwicke and E. Pickwell-MacPherson
Appl. Phys. Lett. 118, 230501 (June 2021)
It was first suggested that terahertz imaging has the potential to detect skin cancer twenty years ago. Since then, THz instrumentation has improved significantly: real time broadband THz imaging is now possible and robust protocols for measuring living subjects have been developed. Here, we discuss the progress that has been made as well as highlight the remaining challenges for applying THz imaging to skin cancer detection.
A. I. Hernandez-Serrano and E. Pickwell-MacPherson
Scientific Reports 11, 3005 (February 2021)
In this work we demonstrate a triangular surface lens (axicon) operating at frequencies between 350 and 450 GHz using parallel-plate-waveguide technology. The proposed axicon offers longer focal depth characteristics compared to conventional plastic lenses, surpassing common TPX lenses by one order of magnitude. Additionally, due to the triangular surface of the axicon, this device is able to focus THz radiation onto smaller areas than TPX lenses, enhancing the resolution characteristics of THz imaging systems. The frequency range of operation of the proposed axicon can be easily tuned by changing the space between plates, making this approach a very attractive candidate for low-cost, robust and easy to assemble solutions for the next generation of active THz devices.
H. Lindley-Hatcher, A. I. Hernandez-Serrano, J. Wang, J. Cebrian, J. Hardwicke and E. Pickwell-MacPherson
J. Phys. Photonics 3, 014001 (December 2020)
Terahertz (THz) in vivo reflection imaging can be used to assess the water content of the surface of the skin. This study presents the results of treating 20 subjects with aqueous, anhydrous and water-oil emulsion samples and observing the changes induced in the skin using THz sensing. These regions were also measured with a corneometer, the present gold standard for skin hydration assessment within the cosmetics industry. We find that THz sensing is effective at observing the presence of oil and water on the surface of the skin, these results can be verified with the measurements of capacitance taken by the corneometer. The THz measurements reveal a distinction between the responses of subjects with initially dry or well hydrated skin, this observation is particularly noticeable with the oil-based samples. Additionally, moderate correlation was found between the THz reflected amplitude and capacitance of untreated skin with a correlation coefficient of r = −0.66, suggesting THz sensing has promising potential for assessing skin hydration.
X. Chen, Q. Sun, J. Wang, H. Lindley-Hatcher, E. Pickwell-MacPherson
Adv. Photonics Res. 2000024 (November 2020) [ pdf ] [ ref ]
The noninvasive and water‐sensitive characteristics of terahertz (THz) light make it highly attractive for in vivo studies, especially for skin applications. However, THz instrumentation has not been developed sufficiently to fully explore all the potential applications arising: current systems cannot obtain uncorrelated reflections from multiple configurations to determine the complicated structure of living tissues. Herein, this bottleneck is overcome by implementing a novel ellipsometry configuration able to efficiently provide four complementary sets of spectral ratios, significantly enhancing characterization capabilities. An accurate model of the skin is established and validated. The anisotropy of the stratum corneum (SC) caused by its cellular structure is verified both theoretically and experimentally. The in vivo response of skin on the volar forearm to occlusion is observed by the dynamic changes in the SC and the epidermis. In addition, the THz dispersion and birefringence sensitively probe the level of hydration and the cellular inhomogeneity, producing results in good agreement with microscope images and the biological processes of the SC. The presented technique offers a brand‐new functionality in extracting insightful structural information from complex systems, significantly extending the versatility of THz spectroscopy.
J. Wang, H. Lindley-Hatcher, K. Liu, E. Pickwell-MacPherson
Biomedical Optics Express 11 4484 (August 2020) [ pdf ] [ ref ]
Transdermal drug delivery (TDD) is widely used for painless dosing due to its minimally invasive nature compared to hypodermic needle injection and its avoidance of the gastrointestinal tract. However, the stratum corneum obstructs the permeation of drugs into skin. Microneedle and nanoneedle patches are ways to enhance this permeation. In this work, terahertz (THz) imaging is utilized to compare the efficacy of different TDD methods including topical application and via a needle patch. Our work shows the feasibility and potential of using THz imaging to quantify and evaluate different transdermal application methods.
A. I. Hernandez-Serrano, S. J. Leigh and E. Pickwell-MacPherson
OSA Continuum 3, 2407 (August 2020)
In this research, we present the design, fabrication, and experimental validation of 3D printed bandpass filters and mux/demux elements for terahertz frequencies. The filters consist of a set of in-line polystyrene (PS) rectangular waveguides, separated by 100 µm, 200 µm, and 400 µm air gaps. The principle of operation for the proposed filters resides in coupled-mode theory. Q-factors of up to 3.4 are observed, and additionally, the experimental evidence demonstrates that the Q-factor of the filters can be improved by adding fiber elements to the design. Finally, using two independent THz broadband channels, we demonstrate the first mux/demux device based on 3D printed in-line filters for the THz range. This approach represents a fast, robust, and low-cost solution for the next generation of THz devices for communications.
R. I. Stantchev, X. Yu, T. Blu and E. Pickwell-MacPherson
Nature Communications 11 2535 (May 2020) [ pdf ] [ ref ]
Terahertz (THz) radiation is poised to have an essential role in many imaging applications, from industrial inspections to medical diagnosis. However, commercialization is prevented by impractical and expensive THz instrumentation. Single-pixel cameras have emerged as alternatives to multi-pixel cameras due to reduced costs and superior durability. Here, by optimizing the modulation geometry and post-processing algorithms, we demonstrate the acquisition of a THz-video (32 × 32 pixels at 6 frames-per-second), shown in real-time, using a single-pixel fiber-coupled photoconductive THz detector. A laser diode with a digital micromirror device shining visible light onto silicon acts as the spatial THz modulator. We mathematically account for the temporal response of the system, reduce noise with a lock-in free carrier-wave modulation and realize quick, noise-robust image undersampling. Since our modifications do not impose intricate manufacturing, require long post-processing, nor sacrifice the time-resolving capabilities of THz-spectrometers, their greatest asset, this work has the potential to serve as a foundation for all future single-pixel THz imaging systems.
A. I Hernandez-Serrano, D. M. Mittleman and E. Pickwell-MacPherson
Optics Letters 45 1208 (Feb 2020) [ pdf ] [ ref ]
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.
H. Lindley-Hatcher, A. I Hernandez-Serrano, Q. Sun, J. Wang, J. Cebrian, L. Blasco, E. Pickwell-MacPherson
J Infrared Milli Terahz Waves 40 980 (August 2019) [ pdf ] [ ref ]
This work presents an experimental setup to control the way in which pressure interferes with the repeatability of in vivo THz skin measurements. By integrating a pressure sensor circuit into our THz system, it is possible to identify which measurements were taken within a previously specified pressure range. The live response of the pressure sensor helps to acquire data within the desired pressure leading to greater consistency of data between measurements. Additionally, a protocol is proposed to help achieve repeatable results and to remove the effects of the natural variation of the skin through the course of the day. This technique has been shown to be able to quantify the changes induced in the skin following the application of a moisturising skin product and shows the measured result to be significantly different from natural skin variation. This research therefore prepares the way for further studies on the effectiveness of different skin products using in vivo THz measurements.
C.D.W. Mosley, M. Staniforth, A. I. Hernandez Serrano, E. Pickwell-MacPherson and J. Lloyd-Hughes
AIP Advances 9, 045323 (Apr 2019) [ pdf ] [ ref ]
A multi-element interdigitated photoconductive emitter for broadband THz polarization rotation is proposed and experimentally verified. The device consists of separate pixels for the emission of horizontally and vertically polarized THz radiation. The broadband (0.3–5.0 THz) nature of the device is demonstrated, and the polarization angle of the generated far-field THz radiation is shown to be readily controlled by varying the relative bias voltage applied to the horizontally and vertically emitting pixels. The device is scalable in design, and with its simple method of polarization rotation it allows the modulation of the generated THz polarization at rates significantly faster than those achievable in ellipsometry systems based on mechanically rotating components.
Q. Sun, K. Liu, X. Chen, X. Liu, A. I Hernandez-Serrano, E. Pickwell-MacPherson
Optics Letters 44 2149 (April 2019) [ pdf ] [ ref ]
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.I. Hernandez-Serrano, Q. Sun, E.G. Bishop, E.R. Griffiths, C.P. Purssel, S.J. Leigh, J. Lloyd-Hughes and E. Pickwell-MacPherson
Optics Express 27 8 11635 (April 2019) [ pdf ] [ ref ]
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.
Z. Chen, X. Chen, L. Tao, K. Chen, M. Long, K. Yan, R.I. Stantchev, E. Pickwell-MacPherson & J.-B. Xu
Nature Communications 9 4909 (November 2018) [ pdf ] [ ref ]
Terahertz modulators with high tunability of both intensity and phase are essential for effective control of electromagnetic properties. Due to the underlying physics behind existing approaches there is still a lack of broadband devices able to achieve deep modulation. Here, we demonstrate the effect of tunable Brewster angle controlled by graphene, and develop a highly-tunable solid-state graphene/quartz modulator based on this mechanism. The Brewster angle of the device can be tuned by varying the conductivity of the graphene through an electrical gate. In this way, we achieve near perfect intensity modulation with spectrally flat modulation depth of 99.3 to 99.9 percent and phase tunability of up to 140 degree in the frequency range from 0.5 to 1.6 THz. Different from using electromagnetic resonance effects (for example, metamaterials), this principle ensures that our device can operate in ultra-broadband. Thus it is an effective principle for terahertz modulation.
Q. Sun, X. Liu, J. Cao, R.I. Stantchev, Y. Zhou, X. Chen, E.P.J. Parrott, J. Lloyd-Hughes, N. Zhao, and E. Pickwell-MacPherson
J. Phys. Chem. C 122 17552 (June 2018) [ pdf ] [ ref ]
Terahertz (THz) thin-film total internal reflection (TF-TIR) spectroscopy is shown to have an enhanced sensitivity to the vibrational properties of thin films in comparison with standard THz transmission spectroscopy. This increased sensitivity was used to track photoinduced modifications to the structure of thin films of methylammonium (MA) lead halide, MAPbI3–xBrx (x = 0, 0.5, 1, and 3). Initially, illumination strengthened the phonon modes around 2 THz, associated with Pb–I stretch modes coupled to the MA ions, whereas the 1 THz twist modes of the inorganic octahedra did not alter in strength. Under longer term illumination, the 1 THz phonon modes of encapsulated films slowly reduced in strength, whereas in films exposed to moisture and oxygen, these phonons weaken more rapidly and blue-shift in frequency. The rapid monitoring of environmentally induced changes to the vibrational modes afforded by TF-TIR spectroscopy offers applications in the characterization and quality control of the perovskite thin-film solar cells and other thin-film semiconductors.