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.
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.
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.
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.
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.