Further evidence that far-UVC for disinfection is unlikely to cause erythema or pre-mutagenic DNA lesions in skin

Funding: UK EPRSC PhD studentship (EP/N509759/1) and Medi-lase (SC037390).It is well understood that ultraviolet‐C (UVC) radiation is effective for the destruction of micro‐organisms and drug‐resistant bacteria and is being investigated for its effectiveness at destroying the virus responsible for the current Covid‐19 global pandemic. Far‐UVC (200 ‐ 220 nm) has been proposed as an effective disinfection radiation that is safe to humans. In 2014, Woods et al. undertook a first‐in‐person study to assess the effect on skin of a 222 nm UVC emitting device (Sterilray disinfectant wand, Healthy Environment Innovations, Dover, NH, USA).Publisher PDFPeer reviewe

Extreme Exposure to Filtered Far-UVC:A Case Study^†

Far-UVC devices are being commercially sold as "safe for humans" for the inactivation of SARS-CoV-2, without supporting human safety data. We felt there was a need for rapid proof-of-concept human self-exposure, to inform future controlled research and promote informed discussion. A Fitzpatrick Skin Type II individual exposed their inner forearms to large radiant exposures from a filtered Krypton-Chloride (KrCl) far-UVC system (SafeZoneUVC, Ushio Inc., Tokyo, Japan) with peak emission at 222 nm. No visible skin changes were observed at 1,500 mJcm-2, whereas skin yellowing that appeared immediately and resolved within 24 hours occurred with a 6,000 mJcm-2 exposure. No erythema was observed at any time point with exposures up to 18,000 mJcm-2. These results combined with Monte Carlo Radiative Transfer computer modelling suggest that filtering longer ultraviolet wavelengths is critical for the human skin safety of far-UVC devices. This work also contributes to growing arguments for the exploration of exposure limit expansion, which would subsequently enable faster inactivation of viruses.Publisher PDFPeer reviewe

Computer Modeling Indicates Dramatically Less DNA Damage from Far-UVC Krypton Chloride Lamps (222 nm) than from Sunlight Exposure

Funding: Dr Paul O’Mahoney is funded by Medi-lase (registered charity SC037390) and the Alfred Stewart Trust. Dr Isla Barnard acknowledges financial support from an UK EPRSC PhD studentship (EP/N509759/1) and Louise Finlayson acknowledges financial support from EPSRC Industrial Doctorate Centre Scheme (2262922) and the Laser Research and Therapy Fund (registered charity SC030850).This study aims to investigate, with computer modeling, the DNA damage (assessed by cyclobutane pyrimidine dimer (CPD) formation) from far-ultraviolet C (far-UVC) in comparison with sunlight exposure in both a temperate (Harwell, England) and Mediterranean (Thessaloniki, Greece) climate. The research utilizes the published results from Barnard et al. [Barnard, I.R.M (2020) Photodermatol. Photoimmunol. Photomed. 36, 476?477] to determine the relative CPD yield of unfiltered and filtered far-UVC and sunlight exposure. Under current American Conference of Governmental Industrial Hygienists (ACGIH) exposure limits, 10 minutes of sunlight at an ultraviolet (UV) Index of 4 ? typical throughout the day in a temperate climate from Spring to Autumn - produces equivalent numbers of CPD as 700 hours of unfiltered far-UVC or more than 30,000 hours of filtered far-UVC at the basal layer. At the top of the epidermis these values are reduced to 30 and 300 hours respectively. In terms of DNA damage induction, as assessed by CPD formation, the risk from sunlight exposure greatly exceeds the risk from far-UVC. However the photochemistry that will occur in the stratum corneum from absorption of the vast majority of the high energy far-UVC photons is unknown, as are the consequences.Publisher PDFPeer reviewe

Imaging in thick samples, a phased Monte Carlo radiation transfer algorithm

This work was supported by the EPSRC (Grant No. EP/K503162/1).Significance : Optical microscopy is characterized by the ability to get high resolution, below 1  μm, high contrast, functional and quantitative images. The use of shaped illumination, such as with lightsheet microscopy, has led to greater three-dimensional isotropic resolution with low phototoxicity. However, in most complex samples and tissues, optical imaging is limited by scattering. Many solutions to this issue have been proposed, from using passive approaches such as Bessel beam illumination to active methods incorporating aberration correction, but making fair comparisons between different approaches has proven to be challenging. Aim : We present a phase-encoded Monte Carlo radiation transfer algorithm (φMC) capable of comparing the merits of different illumination strategies or predicting the performance of an individual approach. Approach : We show that φMC is capable of modeling interference phenomena such as Gaussian or Bessel beams and compare the model with experiment. Results : Using this verified model, we show that, for a sample with homogeneously distributed scatterers, there is no inherent advantage to illuminating a sample with a conical wave (Bessel beam) instead of a spherical wave (Gaussian beam), except for maintaining a greater depth of focus. Conclusion : φMC is adaptable to any illumination geometry, sample property, or beam type (such as fractal or layered scatterer distribution) and as such provides a powerful predictive tool for optical imaging in thick samples.Publisher PDFPeer reviewe

Local sensing of absolute refractive index during protein-binding using microlasers with spectral encoding

Funding: Engineering and Physical Sciences Research Council - EP/P030017/1; Alexander von Humboldt-Stiftung; European Research Council - 640012; Royal Society - DH160102.Multiplexed, specific, and sensitive detection of antigens is critical for the rapid and accurate diagnosis of disease and the informed development of personalized treatment plans. Here, it is shown that polymer microsphere lasers can be used as photonic sensors to monitor and quantify direct surface binding of biomolecules via changes in the refractive index. The unique spectral signature of each individual laser can be used to find their size and effective refractive index which adds a new encoding dimension when compared to conventional fluorescent beads. Antibody-functionalized microlasers selectively detect protein binding, as demonstrated for Immunoglobulin G and C-reactive protein, and have the ability to resolve different stages of the multilayer surface modification. Moreover, by continuously monitoring single lasers, the possibility of real-time monitoring of binding dynamics between antigens in solution phase and the immobilized antibodies is demonstrated. For multiplexed detection, the microlasers are employed in a flow cytometer configuration, with fast spectral detection and identification of microlasers with and without antigen binding. It is envisioned that by combining microlasers with well-established surface modification chemistries and flow geometries, the multiplexing ability of microbead immunoassays can be strongly increased while also opening avenues for single-cell profiling within heterogeneous cell populations.Publisher PDFPeer reviewe

Development of a predictive Monte Carlo radiative transfer model for ablative fractional skin lasers

L.M. would like to acknowledge the funding from EPSRC grant code: EP/K503162/1. P.O'M. is funded by Medi‐Lase (registered charity SC 037390) and the Alfred Stewart Trust'.It is possible to enhance topical drug delivery by pretreatment of the skin with ablative fractional lasers (AFLs). However, the parameters to use for a given AFL to achieve the desired depth of ablation or the desired therapeutic or cosmetic outcome are hard to predict. This leaves open the real possibility of overapplication or underapplication of laser energy to the skin. In this study, we developed a numerical model consisting of a Monte Carlo radiative transfer (MCRT) code coupled to a heat transfer and tissue damage algorithm. The simulation is designed to predict the depth effects of AFL on the skin, verified with in vitro experiments in porcine skin via optical coherence tomography (OCT) imaging. Ex vivo porcine skin is irradiated with increasing energies (50–400 mJ/pixel) from a CO2 AFL. The depth of microscopic treatment zones is measured and compared with our numerical model. The data from the OCT images and MCRT model complement each other well. Nonablative thermal effects on surrounding tissue are also discussed. This model, therefore, provides an initial step toward a predictive determination of the effects of AFL on the skin.Publisher PDFPeer reviewe

Microlaser-based contractility sensing in single cardiomyocytes and whole hearts

Microscopic whispering gallery mode lasers detect minute changes in cellular refractive index inside individual cardiac cells and in live zebrafish. We show that these signals encode cardiac contractility that can be used for intravital sensing.Postprin

Local Sensing of Absolute Refractive Index During Protein-Binding using Microlasers with Spectral Encoding

Multiplexed, specific, and sensitive detection of antigens is critical for the rapid and accurate diagnosis of disease and the informed development of personalized treatment plans. Here, it is shown that polymer microsphere lasers can be used as photonic sensors to monitor and quantify direct surface binding of biomolecules via changes in the refractive index. The unique spectral signature of each individual laser can be used to find their size and effective refractive index which adds a new encoding dimension when compared to conventional fluorescent beads. Antibody-functionalized microlasers selectively detect protein binding, as demonstrated for Immunoglobulin G and C-reactive protein, and have the ability to resolve different stages of the multilayer surface modification. Moreover, by continuously monitoring single lasers, the possibility of real-time monitoring of binding dynamics between antigens in solution phase and the immobilized antibodies is demonstrated. For multiplexed detection, the microlasers are employed in a flow cytometer configuration, with fast spectral detection and identification of microlasers with and without antigen binding. It is envisioned that by combining microlasers with well-established surface modification chemistries and flow geometries, the multiplexing ability of microbead immunoassays can be strongly increased while also opening avenues for single-cell profiling within heterogeneous cell populations

Computational simulations of ultraviolet radiation penetration into human skin

This thesis concerns the development of numerical modelling simulations to predict how ultraviolet radiation (UVR) penetrates into human skin in a wavelength dependent manner. UVR has biological effects; for example, UVR causes damage to DNA within skin cells, and these effects are wavelength dependent. A Monte Carlo Radiative Transfer (MCRT) model was developed in order to simulate the transport of UVR from different radiation sources through the upper layers of human skin. Using the results of these simulations, the depth to which different wavelengths of UVR penetrate can be examined, and then resulting biological effects can be predicted. The research presented here quantifies DNA damage occurring due to sunbed use, investigates the protective effects of melanin and sunscreen, investigates potential novel lamps for psoriasis treatment and examines the safety of UVR sterilisation devices. In addition, research is presented from practical work, evaluating the performance of a handheld UVR meter when used to measure UVR output from commercial sunbeds."This work was supported by an UK EPRSC PhD studentship [EP/N509759/1] and MediLase, the Medical Laser Research Fund (Registered Charity SC037390)." -- Fundin

Further evidence that far-UVC for disinfection is unlikely to cause erythema or pre-mutagenic DNA lesions in skin

It is well understood that ultraviolet‐C (UVC) radiation is effective for the destruction of micro‐organisms and drug‐resistant bacteria and is being investigated for its effectiveness at destroying the virus responsible for the current Covid‐19 global pandemic.Far‐UVC (200 ‐ 220 nm) has been proposed as an effective disinfection radiation that is safe to humans. In 2014, Woods et al. undertook a first‐in‐person study to assess the effect on skin of a 222 nm UVC emitting device (Sterilray disinfectant wand, Healthy Environment Innovations, Dover, NH, USA)