Terahertz skinometer for improved cancer prevention and treatment

Lead Research Organisation: University of Warwick
Department Name: Physics

Abstract

The incidence of skin cancer in the UK and globally is increasing. There are two main types of skin cancer: melanoma and non-melanoma skin cancer. Basal Cell Carcinoma (BCC) is a non-melanoma skin cancer, and is the most common type (> 80%) of all UK skin cancer cases. It is well known that applying sunscreen helps to protect the skin from the sun but many people are unaware of the need for UVA (315-400 nm) as well as UVB (280-315 nm) protection. Although lower in energy than UVB, the amount of UVA reaching the earth's surface is 30 times more than for UVB. Furthermore, UVA penetrates the skin more deeply, contributing to both carcinogenesis and skin aging via oxidative stress pathways. One of the most common UVA filters is avobenzone, as it is industrially cheap and thus affordable to the consumer. However, it is now well-established that avobenzone photodegrades, which is a serious concern.

In this project, a highly interdisciplinary team consisting of investigators at the University of Warwick in the Departments of Physics, Chemistry, Life Sciences and Medicine, as well as industry partners from Lubrizol (major skin-care provider) and TeraView Ltd (major terahertz (THz)-based instrument provider) will join forces to attack the problem of increasing skin cancer 'prevention' and 'treatment' using a multi-pronged approach. We will improve skin cancer prevention by developing a new UVA, nature-inspired, sunscreen offering longer lasting and more photostable protection than existing sunscreens. To achieve this, we will repurpose the photoprotection mechanisms of other living organisms, specifically those of cyanobacteria and microalgae. These organisms protect themselves from radiation by producing mycosporine-like amino acids (MAAs), a family of molecules which are strong UVA absorbers and are ideal candidates for sunscreen agents, owing to their dual action as UVA filter and antioxidant.

We recognise that sunscreens are composed of a UV filter blended with a moisturiser (emollient); this can make up to 80% of the composition of the sunscreen. We also recognise that sunscreens are applied to skin. Therefore, to optimise the sunscreen composition, we will develop a revolutionary characterisation tool, the 'THz skinometer', which is able to measure parameters of skin in vivo that other techniques cannot. In this way, we will determine the best UV filter/emollient blend. We will investigate whether different skin conditions such as eczema and psoriasis will benefit from a different emollient blend. THz radiation is non-ionising, using low power levels such that thermal effects are insignificant and consequently safe for in vivo imaging of humans as well as non-destructive testing of materials. It is very sensitive to intermolecular interactions such as hydrogen bonds, and probes molecular processes (eg vibrations, chemical reactions) that occur on picosecond (millionth millionth of a second) timescales. In this project we will employ THz techniques to evaluate the effectiveness of emollients and sunscreens in vivo with a view to developing a single sunscreen that covers both the UVA and UVB regions of the solar spectrum.

Furthermore, as a powerful additional feature of our invention, we will also use our THz skinometer to improve the surgical removal, or 'treatment', of skin cancers such as BCC, which often spread out beneath the surface of the skin such that their entirety cannot be detected until surgery. The THz skinometer will be designed to accurately characterise skin in vivo such that it will be able to determine the likely extent of any tumour beneath the surface. In this way, we will identify the full extent of the tumour prior to surgery which will improve skin grafting planning as well as reduce the likelihood of missing any tumour and tumour recurrence. Thus by attacking skin cancer through 'prevention' as well as 'treatment', we aim to reduce 'incidence' and 'morbidity' of skin cancer in the UK & globally.

Planned Impact

During (and post) tenure of the grant, we anticipate that the proposed research will impact 'knowledge', 'economy', 'society' and 'people':

Knowledge: The radically new THz skinometer developed will be able to quantitatively measure a unique combination of skin properties including the diffusivity of occluded skin - no other existing technologies can do this hitherto; this will therefore be a powerful new tool for clinicians including dermatologists and skin-care researchers for improving diagnosis, monitoring and treatment of skin conditions. Furthermore, the THz skinometer will also be able to determine the extent of a skin cancer (including areas which are subclinical and not visible using existing technologies) prior to surgery thus facilitating surgeons (and associated staff) planning and reducing patient trauma. Finally, the algorithms developed will be of great significance to the academic community; it will open up a new avenue of in vivo skin research which will be relevant to skin product development as well as skin diagnosis and treatment planning.

On the sunscreen side, the project will investigate photoprotection mechanisms of MAAs, their interaction with emollients and the emollient penetration and hydration of skin. This has the potential to inform researchers using 'top-down' methodologies to develop next generation UVA sunscreens that are suitably robust to photodegradation and optimally designed for normal skin as well as other skin types, since more effective sunscreen will lead to better prevention of skin cancer. As well as optimising sunscreen development, we will also be able to give quantitative feedback on capabilities of moisturisers when used to treat skin conditions such as eczema and psoriasis. Such knowledge is once again crucial to researchers working in the field of skin-care.

Economy: Two major companies are project partners in this proposed research. Lubrizol, a major skin-care provider is greatly interested in our approach, (see letter of support) and the team will look to grow these links during the tenure of the grant and beyond, along with existing links with clinical collaborators at University Hospitals Coventry and Warwickshire (UHCW). Likewise, the development of a new powerful THz imaging capability with TeraView, our second industry project partner, who is internationally known as a leading THz instrument provider, may also lead to the development of a new imaging product. Thus the link with these two industry project partners may have major ramifications to Economy.

Society: The development of a new sunscreen with improved optical properties including increased absorption strength, spectral coverage and photostability will mean that lower concentrations of these sunscreens are added to the formulation. This means that the same sun protection factor (SPF) rating can be achieved whilst reducing the complexity of sunscreens and thus the potential for adverse side-effects (improved healthcare) and thus substantial savings to the skin-care industry (economy). Likewise, the development of the THz skinometer will aid skin diagnosis and treatment planning. This may lead to increased throughput and/or cost savings in the NHS, or even reduction in demand for treatment. It could also shift clinical diagnosis from hospitals to primary providers (GPs), with consequently improved efficiencies.

The proposed work will thus generate multiple synergies with the EPSRC's Healthcare Technologies theme and support the Healthcare Technologies Grand Challenges, namely Frontiers of Physical Intervention, Optimising Treatment, Transforming Community Health and Care and Developing Future Therapies.

People: The interdisciplinary training and development of one PDRA and two PhD students will help to create a talent pool to drive key emerging industries for our future. These talented scientists will also contribute to shaping and inspiring future research addressing healthcare challenges.

Publications

10 25 50
 
Description Our key finding so far is that we have shown that the protocol we have developed for in vivo THz imaging can detect subtle changes in skin that help our understanding of how skin products interact with the skin - a necessary step for development of new products such as sunscreens.

We have recently done the first in vivo THz ellipsometry measurement of human skin and shown that the THz birefringence is non-zero. This provides us with yet another unique and sensitive parameter with which to characterise skin.
Exploitation Route Others in the skin care industry may want to use THz imaging to test and evaluate their products.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Robust THz imaging of skin protocol
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Lubrizol 
Organisation The Lubrizol Corporation
Country United States 
Sector Private 
PI Contribution We have developed a robust protocol for measuring the THz properties of skin in vivo. My research team is able to calibrate the THz data to account for fluctuations in THz power and system issues, and Lubrizol have shown us a good way to account for any physiological changes that might affect the results. We are using this technique to try to quantitatively measure the effects of different skin products such as moisturisers. PhD student Hannah Hatcher has visited the lab at Lubrizol, Spain, to learn more about skin testing protocols.
Collaborator Contribution Lubrizol has provided components of moisturisers which we have measured using 3 different techniques before and after application to the skin. Lubrizol came to our lab to help with the measurements and brought their corneometer and transepidermal water loss probes. The third measurement was with our existing THz imaging system. We are working with them to analyse the data.
Impact We have published one journal paper on the robust protocol method and we are working on another paper about the moisturiser study.
Start Year 2019
 
Description TeraView Ltd 
Organisation Teraview Ltd
Country United Kingdom 
Sector Private 
PI Contribution The development of our robust imaging protocols is of interest to TeraView and I have presented this work to them.
Collaborator Contribution TeraView Ltd has built THz probes able to do non-contact measurements (designed for other applications such as car paint quality control) and their insight into non-contact measurements is useful for the development of the THz skinometer. In summer 2019, they have shown me a couple of their non-contact THz systems.
Impact It is early days for our recent collaboration on Thz instrumentation, but we have bought a similar proximity sensor to the one that TeravIew use and will incorporate it into our Thz skinometer.
Start Year 2019
 
Title Thz skinometer 
Description The THz skinometer is at the stage of being able to do pressure controlled contact measurements of skin on easily accessible areas such as the volar forearm. We are actively working to extend this to other locations of skin and also to be able to do non-contact imaging. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2020
Development Status Under active development/distribution
Impact So far we have been using the basic skinometer probe to characterise normal skin and determine its hydration. We can also quantitatively measure how skin products affect the skin's properties. 
 
Description Will give a talk to the Warwick University Skin Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact My talk to the skin society is scheduled for 10th March 2021. It will create a broader awareness of our reserach and may help in the long run for accepting new technologies for skin care and diagnosis.
It may also hep us recruit volunteers for our skin studies.
Year(s) Of Engagement Activity 2021