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Japanese Journal of Applied Physics 60, 100501 (2021) STAP REVIEW
https://doi.org/10.35848/1347-4065/ac1f47 Deep ultraviolet light sources for post-COVID-19 sustainable society

Application of ultraviolet light sources for in vivo disinfection

Yiyu Ou* and Paul Michael Petersen
Department of Photonics Engineering, Technical University of Denmark, Ørsteds plads 343, Kgs. Lyngby, DK-2800, Denmark
*
E-mail: [email protected]
Received May 27, 2021; revised July 9, 2021; accepted August 18, 2021; published online September 17, 2021

Development of antibiotic resistance is a major challenge for antibiotics as an effective treatment approach of infectious diseases and pathogenic
microbes with resistance to antibiotics will become difficult to be treated. Therefore, a new therapy method, which is safe and can inactivate
pathogenic microbes effectively without developing a resistance, is highly needed. Ultraviolet irradiation is well known for its ability of effective
microbial inactivation and it is widely used in sterilization of inanimate objects based on conventional ultraviolet light sources. Meanwhile, applying
ultraviolet irradiation in human disinfection application is an emerging and rapidly progressing field. This review focuses on recent studies in
ultraviolet based disinfection methods including both animal and human studies. We will introduce different microbial inactivation mechanisms,
which are associated with the ultraviolet irradiation wavelength. Relevant research work will be summarized with a focus on their microbial
inactivation effect and safety issues. © 2021 The Japan Society of Applied Physics

Infectious disease is one of the major burdens of the

1. Introduction world’s healthcare system. Especially for developing coun-
Ultraviolet (UV) radiation is part of the electromagnetic tries, five types of infectious diseases are among the top ten
spectrum and has a shorter wavelength than visible light and causes of death for humans.8) Broad-spectrum antibiotics is
a longer wavelength than X-rays. It is often classified into an effective disinfection approach that can significantly lower
three bands: UVA (315–400 nm), UVB (280–315 nm), and the mortality rate of the infectious diseases. However,
UVC (100–280 nm), which can be utilized in various pathogens could also develop a resistance to the antibiotics
applications depending on the different biological effect. and then become difficult to be treated. Over the last 60
Today, UVA is commonly used in UV curing, UV litho- years, the development of antibiotic resistance has acceler-
graphy and UV sensing; UVB can be used in food industry ated due to many factors such as overuse and inappropriate
(i.e. Vitamin D production), medical (i.e. skin cure, disin- use of antibiotics.9) Infections caused by antibiotic resistant
fection) and agriculture (i.e. plant growth lighting) applica- microbes are often hard to treat due to the limited therapy
tions; while UVC is often used in water purification, surface options.10) For example, surgical site infection (SSI) is one of
sterilization and disinfection.1,2) the most severe complications arisen from surgical treatment
Among all the applications, UV disinfection and steriliza- and it is often associated with Staphylococcus aureus.
tion has the longest history and is probably one of the most Methicillin-resistant Staphylococcus aureus (MRSA) shows
important UV applications. Back in the 19th century, scientists resistance to multiply antibiotics and MRSA caused SSI has
discovered the bactericidal effect of UV part of the Sun light, already become a major clinical challenge.11) Therefore, there
which can inhibit the growth of various kinds of bacteria.3) is an urgent need for new approaches that can inactivate
Since then, UV irradiation has been proven as a highly pathogens effectively without harming healthy cells and
efficient, inexpensive and reliable disinfection and sterilization developing a resistance. UV irradiation shows a non-specific
method without adding toxic chemicals, changing composi- microbial inactivation effect most likely without developing
tion, or introducing harmful side effects. Especially UVC resistance. It could be a promising therapy method to treat
irradiation is capable of inactivating more that 99.99% infectious disease on human if the safety concerns (mainly
pathogenic microbes within seconds by damaging the deox- for UVC) can be addressed.
yribonucleic acid (DNA) structures and disrupting the DNA This review aims to give an overview of recent in vivo
replication process. Recent research confirms that UVC studies of UV irradiation based disinfection therapy methods,
irradiation has the potential for inactivation of airborne human including both animal and clinical studies. It is well noted
coronaviruses.4,5) Meanwhile, UVB and UVA are also capable that the in vivo UV disinfection is still in its early research
of inactivating microbes based on different mechanisms, but and development stage and the relevant work is much less
are relatively less effective in direct DNA damage. It is than the in vitro UV disinfection. We will introduce different
because the DNA structure has a strong UV absorption in microbial inactivation mechanisms that associated with the
the UVC range with an absorption peak at around 260 nm.6) UV irradiation wavelength and will discuss about the relevant
On the other hand, conventional UVC light source at 254 nm work with a focus on the microbial inactivation effect, safety
can also damage healthy host cells and lead to skin cancer and and application limitations.
cataracts. Therefore, conventional UVC irradiation is a health
hazard while UVA is relatively safe for humans. UVB is in an 2. UV induced DNA damage
intermediate region where depending on the irradiation dose UVC and part of UVB irradiation can inactivate the microbes
some wavelengths are harmful and others are actually bene- such as bacteria, viruses and fungi in a short time by
ficial since the UVB wavelengths play an important role in damaging their DNA structures. The UVC irradiation with
Vitamin D production in humans. Today, UVC irradiation is high photon energy can penetrate through the cell membrane
mainly used for sterilization of inanimate objects (water, air, of the microbes and produce cyclobutane pyrimidine dimers
material surface, etc).7) (CPDs) between the pyrimidine residues in the nucleic acid
100501-1 © 2021 The Japan Society of Applied Physics
Jpn. J. Appl. Phys. 60, 100501 (2021) STAP REVIEW

strands. The formation of the CPDs causes a deformation of microbial inactivation on human and animal cells were well
the DNA molecule and therefore disrupts the multiplication reviewed by Hessling et al.6)
of the DNA structures, which leads to the death of cells.12) Far-UVC irradiation is an effective way to reduce the rate
More importantly, UVC irradiation based microbial inactiva- of SSI such as superficial surgical wound infections without
tion works on unspecific microbes regardless of antibiotic harming the healthy host tissues. Research shows that 222 nm
resistance. irradiation can effectively prevent the MRSA infection on
As conventional UVC light source, a low-pressure mer- superficial skin wounds of mice.11,21) It demonstrated the
cury vapor lamp with an emission peak wavelength at same bactericidal effect as conventional 254 nm UVC
254 nm is considered hazardous to host tissues. However, irradiation but without the associated skin damage (CPD
some research findings suggest that its adverse effects to host formation). Clinical human study shows that 222 nm irradia-
tissues are relatively minor compared to its high eradication tion with minimal erythema dose (MED) up to 500 mJ cm−2
efficiency on pathogens. Dai et al. discovered that 254 nm has a significant bactericidal effect on human skin.22)
UVC irradiation can rapidly eradicate Candida albicans in Animal study of mice show that 222 nm UVC irradiation is
mice with burn infection,13) and Pseudomonas aeruginosa safe for mouse skin and no detectable formation of mutagenic
and S.aureus in mice with cutaneous wound infections.14) CPDs were observed by both acute irradiation (157 mJ cm−2,
DNA lesions were observed after applied UV irradiation, but delivered in 7 h)23) and chronic irradiation (500 mJ cm−2, 3
were quickly repaired by DNA repair enzymes in 24–48 h. A times a week for 10 weeks),17) even by high dose chronic
clinical study also shows that 254 nm UVC irradiation can irradiation (450 mJ/cm/day on days 1, 2, 3, 4, 5, 8, 9 and
reduce wound bacterial burden and facilitate wound healing 10).24) Safety of 207 nm UVC irradiation was also verified in
on patients with chronic ulcer infected with MRSA.15) a similar animal study.25) In addition, far-UVC irradiation
Nevertheless, the chronic irradiation of 254 nm light still shows no harmful effect on the mouse retina with an
presents a great health risk to humans. Therefore, it is irradiance up to 5000 mJ cm−2 at 222 nm and 15000
preferred to avoid employing 254 nm UVC irradiation on mJ cm−2 at 207 nm.26)
humans. Although far-UVC irradiation is safe for host mammalian
In the 1960s, Freeman et al. proposed that UVC irradiation tissues, it is worth noting that the irradiation from current far-
in 220 nm was about 20 times less capable of inducing UVC lamps can still be harmful. Today, most commonly
erythema on human skin than the UVC irradiation in used far-UVC light sources are krypton–chlorine (Kr–Cl)
250 nm.16) It is because, compared with conventional excimer lamps with an emission peak at 222 nm and
254 nm UVC light, UVC irradiation in the spectral range of krypton–bromine (Kr–Br) excimer lamps with an emission
200–230 nm (far-UVC) has a strong protein absorption. As peak at 207 nm. The full width at half maximum (FWHM) of
shown in Fig. 1, far-UVC is too short to penetrate stratum the emission spectra of the excimer lamps is in the range of a
corneum layer (dead cells) of human skin and reach the few nanometers. However, the UV irradiation from the
epidermis layer, where cancer stem cells are considered to excimer lamps has a long wavelength component
reside.17,18) Meanwhile, it is still able to penetrate the (>230 nm) in the emission spectrum which is still capable
membrane and damage the microbes due to the fact that of inducing both erythema and CPD formation in human
microbes (0.1–1 μm) are much smaller than human cells skin.22,27) Therefore, it is important to apply a filter on the
(10–25 μm).6,19) This suggests that far-UVC irradiation has excimer lamps to block any emission with a wavelength
an effective bactericidal performance, with less damaging outside the far-UVC spectral range.21,28)
effect on human skin that is associated with conventional Furthermore, it is generally believed that UV irradiation
254 nm UV irradiation. In addition, it is also considered safe will not develop a resistance of microbes. However, some
for the human retina due to the protection by the cornea researches show that microbes may develop a resistance to
layer.19,20) Therefore, far-UVC irradiation is sometimes UVC irradiation if the exposure is repeated excessively.29)
referred to as “safe UVC irradiation” in respect to human Such resistance is a long-term effect through processes of
health. The in vitro study of far-UVC irradiation based mutation and selection and the associated UVC irradiation is

Fig. 1. (Color online) Penetration of UV irradiation into human skin. Far-UVC (200–230 nm) is completely absorbed by the stratum corneum layer,
conventional UVC at 254 nm can reach the epidermis, most part of UVB is absorbed by the epidermis, and UVA can penetrate into the dermis.

100501-2 © 2021 The Japan Society of Applied Physics

Jpn. J. Appl. Phys. 60, 100501 (2021) STAP REVIEW

much higher than the exposure limit for humans.30) the barrier recovery and AMPs expression were mediated
Therefore, more knowledge about the long-term effect of through increased cutaneous vitamin D3 production, which is
UVC irradiation is needed. also a result of UVB irradiation that confirmed in this study.
Using vitamin D synthesized by UVB irradiation to
3. UV induced immune system modulation upregulate the AMPs expression is also studied in a human
Another UV irradiation based microbial inactivation me- model by Mallbris et al.46) After a UVB irradiation (280–
chanism is an indirect approach by introducing diverse 315 nm, 2.3 mW cm−2) with a single MED dose, both
effects on the immune system, more specifically inducing hCAP18 (whose C-terminal peptide is LL-37) and vitamin
the innate immune response and suppressing the adaptive D receptor (VDR) were found expressed significantly in the
immune response.31,32) It is known that epidermis of the skin samples of volunteers with skin types II and III. This
human skin absorbs nearly 90% of the UVB irradiation.33) As finding indicates that vitamin D may be a natural regulator for
illustrated in Fig. 1, the UVB triggered innate response can hCAP18 expression in the skin. However, the correlation of
induce certain antimicrobial peptides (AMPs) in the kerati- VDR and AMPs is still unclear and some researchers
nocytes, which is the primary cellular component of epi- disagree with this hypothesis.31)
dermis and the AMPs play an essential role in the bacterial
defense system of human.34) For instance, human β-defensin 4. UV based antimicrobial photodynamic inactivation
(hBD)-2 is bactericidal for gram-negative bacteria, psoriasin (aPDI)
can effectively fight against Escherichia coli, human cathe- The mechanism of UV irradiation based aPDI is mediated by
licidin LL-37 exhibit antimicrobial effect against skin patho- the generation of reactive oxygen species (ROS) which can
gens such as S.aureus and C. albicans, and hBD-3 and make an oxidative damage to a wide range of biomolecules
ribonuclease (RNase) 7 show a broad-spectrum antimicrobial including lipids, proteins and DNA/RNA, as illustrated in
effect against staphylococci such as MRSA and vancomycin- Fig. 2. When the endogenous or exogenous photosensitizer in
resistant Enterococcus faecium.34–37) Therefore, this method microbes absorb an UV photon, it can generate ROS such as
can be an effective and safe approach to regulate certain types hydrogen peroxide (H2O2) and hydroxyl radicals (∙OH) in the
of skin infectious diseases and promote wound healing. presence of oxygen through the electron transfer mechanism
In a clinical study, Gläser et al. demonstrated the induction (type I), or singlet oxygen (1O2) through the energy transfer
of multiple AMPs in human skin after UVB irradiation.31) mechanism (type II).47,48) The formation of ROS leads to the
Subjects with skin types II and III were irradiated by UVB oxidative damage effect such as peroxidation of lipid,
light with a peak wavelength at 313 nm in different dose level disruption of cell membrane, and denaturation of protein,
(250–1500 J m−2). Punch biopsies of skin in the buttocks which ultimately result in lethal damage of cells.7,47,49) The
area were taken before and 1 and 6 d after UV exposure. It is UV based aPDI can be used to treat not only dermatological
found that hBD-3, RNase 7 and psoriasin were expressed in diseases but also for internal infection applications.
all the samples and the expression of hBD-2 was found in Recent investigation conducted by Rezaie et al. demon-
only one individual. In addition, enhanced expression of strates an effective inactivation on various bacteria
AMPs were detected in samples obtained even 6 d after the (P. aeruginosa, Klebsiella pneumoniae, E. coli,
UV exposure. A similar clinical study conducted by the same Enterococcus faecalis, Clostridioides difficile, Streptococcus
research group shows that hBD-3, RNase 7 and psoriasin pyogenes, S. epidermidis, Proteus mirabilis), yeast
expression have no correlation with the age of the patients (C. albicans) and viruses (Coronavirus-229E and
while hBD-2 expression was detected more frequently in Coxsackievirus B) in vitro by UVA irradiation.50) In vivo
older individuals.38) safety studies show that both single (2.0 mW cm−2 for 30 min)
Some clinical studies show that UVB irradiation can and repeated (3.0–3.5 mW cm−2, 20 min daily for 2 consecu-
decreases the S.aureus carriage in patients with atopic tive days) intracolonic UVA exposure are safe for mice based
dermatitis39–41) but has no effect on Staphylococcus on the endoscopic examination and full-thickness pathologic
epidermidis.39) It can also modulate the expression of hBD- assessment results.
1 and hBD-2 for atopic eczema,42) and improve psoriasis43)
and atopic dermatitis via regulated expression of hBD-2 and
LL-37.44)
The UVB induced expression of mouse β-defensin
(mBD)-3 and cathelin-related antimicrobial peptide
(CRAMP) which are the murine homologs of hBD-2 and
LL-37, respectively, were demonstrated in a mouse model.45)
The study was conducted on female hairless mice which were
exposed to low doses UVB irradiation (40 mJ cm−2, equiva-
lent to 1/2 MED) daily for 1 or 3 d. Real-time reverse
transcription polymerase chain reaction, western blot and
immunohistochemical staining results show that the AMPs
expressions were markedly upregulated by the repeated UVB
irradiation and AMPs were found largely localized to the
outer epidermis of murine skin. It is also found that the Fig. 2. (Color online) Mechanisms of reactive oxygen species generation
recovery of permeability barrier function was improved in by UV irradiation: electron transfer mechanism (type I) with the presence of
parallel with AMPs expression. The authors suggested that oxygen and energy transfer mechanism (type II).

100501-3 © 2021 The Japan Society of Applied Physics

Jpn. J. Appl. Phys. 60, 100501 (2021) STAP REVIEW

In addition, UVA irradiation demonstrate an effective UVB irradiation based aPDI can be effective for oral infection
antifungal performance on yeast infection because fungi treatment.
contain porphyrins, which are endogenous photosensitizer
with a strong light absorption at around 400 nm.51) Clinical 5. Summary and outlook
study shows that patient with vulvovaginal candidiasis UV irradiation shows a significant potential of being an effective
present a reduction of inflammation and disappearance of therapy method for infectious disease. UV irradiation in different
symptoms of pruritus and burning after a treatment by UVA wavelength band can inactivate microbes based on different
light emitting diode (LED).52) In the study, a single session mechanisms. UVC and part of UVB irradiation is capable of
UV exposure (400 nm, 3 mW cm−2) was applied within the making a direct damage to microbes by disrupting their DNA
vaginal canal for 30 min and then on vulva part for replication process within a very short time. It shows a high
another 30 min. The patient was reassessed 21 d after the inactivation efficiency on almost all kinds of pathogenic
treatment. microbes even with a low dose level. UVB irradiation could
Recently, endotracheal UVA based aPDI has also been trigger the innate immune response and induce the expression of
investigated in the treatment of SARS-CoV-2 infection on certain AMPs, which can eradicate certain types of microbes.
human patients.53) This preliminary human study was based UVA and part of UVB irradiation, combined with photosensi-
on five newly intubated mechanically ventilated adults with tizer, can generate ROS and lead to an oxidative damage to
SARS-CoV-2 infection, while all subjects scored 9/10 on the pathogenic microbes. Compared with the latter two mechanisms,
World Health Organization (WHO) clinical severity scale UV based DNA damage shows an efficient microbial inactiva-
(10 = death). Controlled UVA LED was adapted to an tion performance on a wider range of microbes. Some recent
endotracheal tube with a size of 7.5 mm or greater. The research findings of animal and clinical studies of UV irradiation
UVA irradiation, with a peak wavelength at around 340 nm based disinfection application are summarized in Table I.
and an irradiance of 2 mW cm−2, was delivered at the level of Apart from the microbial inactivation efficiency, safety of
tracheal mucosa for 20 min daily for 5 d. Four out of five UV irradiation is another major concern for its in vivo
subjects were clinically improved and scored 2, 4, 5, and 7 on disinfection applications. Clinical research confirm that
the WHO scale at day 30 after the treatment. Meanwhile, it is specific wavelengths in the UVB and UVA regions in a
observed that the slope of viral load reduction during UVA reasonable dose are safe for human. They can treat both
treatment correlated with the slope of improvement in clinical dermatological diseases and internal infection in an effective
WHO severity score over time. The results indicate that, and safe way. Meanwhile, unlike conventional 254 nm UVC
endotracheal UVA phototherapy under specific conditions is irradiation, light in far-UVC range is also more safe for both
safe and can deliver a significant reduction in respiratory human skin tissues and eyes. The emerging of the far-UVC
SARS-CoV-2 viral load on human patients. light sources pave a new way for UVC irradiation based
The UVA based aPDI can also be used to treat against SARS- human disinfection. It should be stressed that clinical
CoV-2 virus on human with the assistance of Riboflavin as research also show that unfiltered far-UVC irradiation from
exogenous photosensitizer.54) In this clinical study, 40 patients excimer lamp is still harmful due to the long wavelength
with confirmed SARS-CoV-2 infection were in an early infec- component from its emission spectrum.
tion stage with mild symptoms like fever, dry cough, headache, Today, UV irradiation has already been playing an im-
hard breathing, fatigue etc and were divided into two groups: one portant role in the society. Since the COVID-19 pandemic
experimental group received UVA based aPDI and one control outbreak at the beginning of 2020, UV irradiation has been
group receive conventional care. Patients in the experimental used to inactivate airborne human coronaviruses (in vitro
group took a Riboflavin capsule first and then had dissolved application, UVC) and treat the patients infected with SARS-
Riboflavin solution sprayed on both nostrils and mouth. An CoV-2 virus (in vivo application, UVA). To further explore
UVA/blue LED device (peaks at 375 and 447 nm) was used to the potential of UV irradiation in human disinfection applica-
give a 20 min exposure treatment on nose applicator and then tion, better UV lighting technology is desired. Compare with
another 20 min on mouse applicator. The treatment was repeated mercury vapor lamp and excimer lamp, UV LED and laser
daily for 5 d. Fourteen out of 20 patients had a negative diode (LD) have some well-recognized advantages, which
quantitative polymerase chain reaction (QPCR) test after 5 d of include narrow emission spectral width, flexibility of wave-
aPDI treatment and the other 6 patients showed a significant length engineering, compact device size, environmentally
reduced clinical symptoms and viral load. In contrast, no friendly, and longer device lifetime. Novel AlGaN-based UV
significant improvement in clinical symptoms and viral load LED can emit UV light in a wide spectral range (210–400 nm)
assessment was observed from all 20 patients in the control that covers from UVC to UVA by tuning the composition in
group. This primary human study shows a potential of UVA the material growth process.1) The device efficiency of UV
based aPDI as an effective approach for treating early stage LED/LD has been continuously improved thanks to the rapid
SARS-CoV-2 infection. progress of III-nitride material technology.58,59)
In addition, it is found that UVB irradiation based aPDI has an It is foreseen that compact UV LED/LD device can be
effective microbial inactivation performance on certain types of utilized not only in dermatological diseases but also in dental
oral bacteria. UVB irradiation at 310 nm can eradicate infection and internal infection treatment in the future via
Porphyromonas gingivalis without introducing a damage to wireless power transmission technology. It is likely, with the
human oral epithelial cells55) and gingival fibroblast.56) UVB development of lighting technology, UV irradiation can be a
irradiation at 296 nm shows a more efficient inactivation on P. long-term effective and safe therapy method for human
aeruginosa than the antibiotics (colistin and tobramycin) and infectious diseases, and can be well adapted to different
conventional UVC irradiation.57) These findings suggest that clinical scenarios.
100501-4 © 2021 The Japan Society of Applied Physics
 Jpn. J. Appl. Phys. 60, 100501 (2021)
Table I. Animal and clinical studies in UV irradiation based disinfection application.

Exposure conditions: irradiance/dose/ Research target: microbe/disease/safety/

Light source time AMP expression Research finding Setting References

UVC: peak at 254 nm 2.7 mW cm−2: • C. albicans burn infection in mice • Exposure in day 0 gives a 99.2% reduction of fungal burden, exposure in day 1 gives a Animal 13
• Mercury lamp 18 min in day 0, or 40 min in day 1 • Safety study 95.8% reduction of fungal burden
• Broadband • CPD were observed by immunofluorescence in normal mouse skin immediately after UV
irradiation, and the damage was extensively repaired within 24 h

UVC: peak at 254 nm 2.7 mW cm−2: • P. aeruginosa and S. aureus cuta- • A 10-fold reduction of the P. aeruginosa and S. aureus burden on mice skin Animal 14
• Mercury lamp 16 min neous wound infections in mice
• Broadband • Safety study • CPD-positive nuclei were observed in the immunofluorescence micrograph of a mouse
skin, and the damage was extensively repaired within 48 h

UVC: peak at 254 nm 180 s; 7 treatments over 14 d + 4 • MRSA infected chronic ulcer on • UVC irradiation reduced wound bacterial burden and facilitated wound healing for all Clinical 15
• Mercury lamp treatments over 1 month human three patients
• Broadband • Two patients had complete wound closure following 1 week of UVC irradiation

UVC: peak at 222 nm 40 mJ cm−2 and 300 mJ cm−2 • MRSA infected superficial skin • Both 222 and 254 nm irradiation show a statistically significant reduction of bacteria Animal 21
• Kr–Cl excimer wound of mice counts on day 2 and day 7
lamp
• FWHM: 2 nm
• •
100501-5

Safety study 222 nm light showed the same bactericidal properties of 254 nm light but without the
UVC: peak at 254 nm associated skin damage (CPD formation)
• Mercury lamp
• Broadband
UVC: peak at 222 nm 75, 150, and 450 mJ cm−2 • MRSA infected skin wound of mice • 222 nm irradiation shows a significant bactericidal effect, which was equal to or more Animal 11
• Kr–Cl excimer effective than 254 nm irradiation
lamp
• FWHM: 2 nm
• Safety study • CPD expressing cells were found in both epidermis and dermis with 254 nm irradiation,
UVC: peak at 254 nm but not with 222 nm irradiation
• Mercury lamp
© 2021 The Japan Society of Applied Physics

• Broadband
UVC: peak at 222 nm 50–500 mJ cm−2 • Bactericidal effect on healthy human • The number of bacterial colonies in the skin swab culture was reduced significantly; Clinical 22
• Kr–Cl excimer skin
lamp • The CPD amount produced in the irradiated region was slightly but significantly higher
• Safety study
• FWHM: 2 nm than that of the non-irradiated region

UVC: peak at 222 nm 157 mJ cm−2: delivered in 7 h • MRSA (in vitro) • Both 254 and 222 nm irradiation can kill MRSA efficiently Animal 23
• Kr–Cl excimer • Safety study (in vivo) • Unlike 254 nm, 222 nm UVC irradiation is safe for mouse skin and no detectable for-
lamp

STAP REVIEW
mation of mutagenic CPDs were observed
• FWHM: 2 nm
UVC: Peak at 254 nm
• Mercury lamp
• Broadband

Continued on next page.

 Jpn. J. Appl. Phys. 60, 100501 (2021)
Table I. Continued.
Exposure conditions: irradiance/dose/ Research target: microbe/disease/safety/
Light source time AMP expression Research finding Setting References

UVB: peak at 313 nm 250–1500 J m−2 • AMP expression • Expression of AMPs (hBD-3, RNase 7 and psoriasin) were detected on all subjects, hBD- Clinical 31
• Fluorescent lamp 2 expression was detected only on one subject.
• FWHM: 41 nm

UVB: 2.3 mW cm−2 • AMP expression • hCAP18 (whose C-terminal peptide is LL-37) was found expressed significantly in the Clinical 46
• Xenon arc lamp human skin
• 280–315 nm

UVB: peak at 313 nm 40 mJ cm−2:daily for 1 or 3 d • AMP expression • Expression of mBD-3, cathelin-related antimicrobial peptide (CRAMP) and LL-37 were Animal 45
• Fluorescent lamp observed
• FWHM: 41 nm • Recovery of permeability barrier function was also improved

UVB: peak at 311 nm Up to 1.6 J cm−2 • Atopic eczema • UVB irradiation can modulate the expression of hBD-1 and hBD-2 for atopic eczema Clinical 42
• Fluorescent lamp • AMP expression
• FWHM: 2.5 nm
UVB: peak at 311 nm 0.13–8.88 J cm−2 • Atopic dermatitis and psoriasis • Enhanced expression of LL-37 and decreased expression of hBD-2 after UVB treatment Clinical 44
• Fluorescent lamp • AMP expression • Significant improvement of psoriasis and atopic dermatitis
• FWHM: 2.5 nm
100501-6

UVB: peak at 306 nm 1.68 J cm−2 • Atopic dermatitis with S. aureus and • The UVB irradiation shows a good antimicrobial effect against S. aureus, but no effect on Clinical 39
• Fluorescent lamp S. epidermidis S. epidermidis.
• FWHM: 34 nm

UVB About 4.3 accumulated joules • Atopic dermatitis with S. aureus • UVB irradiation demonstrates a great suppression of superantigen production from S. Clinical 40
• Narrow band aureus in patients with atopic dermatitis
UVB: peak at 305 nm UVB: 0–100 mJ cm−2 • Atopic dermatitis with S. aureus • UVB and UVA irradiation markedly inhibited the proliferation of S. aureus Clinical 41
• Fluorescent lamp UVA: 0–50 mJ cm−2
UVA: peak at 352 nm
• Fluorescent lamp
© 2021 The Japan Society of Applied Physics

UVA: peak at 400 nm 3 mW cm−2: 30 + 30 min • Vulvovaginal candidiasis • Patient with vulvovaginal candidiasis present a reduction of inflammation and dis- Clinical 52
• LED appearance of symptoms of pruritus and burning after a treatment
• FWHM: 12 nm

UVA: peak at 343 nm 2.0 mW cm−2: 30 min, or 3.0–3.5 mW • Multiple bacteria, yeast, and viruses ( • UVA exposure demonstrates effective inactivation on various bacteria, yeast, and viruses. Animal 50
• LED cm−2: 20 min daily for 2 d in vitro)
• FWHM: 5 nm • Safety study (in vivo) • Single and repeated UVA irradiation are safe for mice based on the endoscopic
examination and full-thickness pathologic assessment results

STAP REVIEW
UVA: peak at 343 nm 2 mW cm−2: 20 min daily for 5 d • SARS-CoV-2 infection • Four out of five subjects were clinically improved at day 30 after the treatment. It shows Clinical 53
• LED that endotracheal UVA phototherapy under specific conditions was safe for human with a
• FWHM: 5 nm significant reduction in respiratory SARS-CoV-2 viral load

UVA: peak at 375 nm 20 + 20 min, repeated daily for 5 d • SARS-CoV-2 infection • 14 out of 20 patients had a negative QPCR test after 5 d of aPDI treatment and the other 6 Clinical 54
• LED patients showed a significant reduced clinical symptoms and viral load.
Jpn. J. Appl. Phys. 60, 100501 (2021) STAP REVIEW

38) M. Wittersheim, J. Cordes, U. Meyer-Hoffert, J. Harder, J. Hedderich, and

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23) M. Buonanno, B. Ponnaiya, D. Welch, M. Stanislauskas, G. Randers- Yiyu Ou received the M.Sc. degree in photonics
Pehrson, L. Smilenov, F. D. Lowy, D. M. Owens, and D. J. Brenner, Radiat. from the Chalmers University of Technology in
Res. 187, 483 (2017). 2009 and the Ph.D. degree in photonics from the
24) K. Narita, K. Asano, Y. Morimoto, T. Igarashi, and A. Nakane, PLoS One
Technical University of Denmark in 2013. In 2013,
13, e0201259 (2018).
he joined Light Extraction Aps (Denmark) as head
25) M. Buonanno, M. Stanislauskas, B. Ponnaiya, A. W. Bigelow, G. Randers-
Pehrson, Y. Xu, I. Shuryak, L. Smilenov, D. M. Owens, and D. J. Brenner,
of technology. Since 2018, he was an assistant
PLoS One 11, e0138418 (2016). professor in the department of photonics engineering
26) S. Kaidzu, K. Sugihara, M. Sasaki, A. Nishiaki, H. Ohashi, T. Igarashi, and at the Technical University of Denmark, and from
M. Tanito, Photochem. Photobiol. 97, 505 (2021). 2020 to present, as an associate professor in photo-
27) J. A. Woods, A. Evans, P. D. Forbes, P. J. Coates, J. Gardner, nics. His current research interest involves semicon-
R. M. Valentine, S. H. Ibbotson, J. Ferguson, C. Fricker, and H. Moseley, ductor materials and devices, nanophotonics, LED
Photodermatol. Photoimmunol. Photomed. 31, 159 (2015). and nanotechnology for biomedical applications.
28) E. Eadie, I. M. R. Barnard, S. H. Ibbotson, and K. Wood, Photochem.
Photobiol. 97, 527 (2021). Paul Michael Petersen received the M.Sc. degree
29) T. Dai, M. S. Vrahas, C. K. Murray, and M. R. Hamblin, Expert Rev. Anti. in engineering and the Ph.D. degree in physics
Infect. Ther. 10, 185 (2012). from the Technical University of Denmark in 1983
30) D. H. Sliney and B. E. Stuck, Photochem. Photobiol. 97, 485 (2021). and 1986, respectively. He has 25 years of research
31) R. Gläser, F. Navid, W. Schuller, C. Jantschitsch, J. Harder, J.-M. Schröder, experience in laser physics, new light sources, and
A. Schwarz, and T. Schwarz, J. Allergy Clin. Immunol. 123, 1117 (2009). biophotonics. From 2002 until 2012 he was
32) J. J. Bernard, R. L. Gallo, and J. Krutmann, Nat. Rev. Immunol. 19, 688 (2019).
adjunct professor in optics at the Niels Bohr
33) A. Reich and K. Mędrek, Int. J. Mol. Sci. 14, 8456 (2013).
Institute, Copenhagen University. From 2001 to
34) J.-M. Schröder and J. Harder, Cell. Mol. Life Sci. 63, 469 (2006).
2008 he was head of Laser systems and Optical
35) J. Harder, J. Bartels, E. Christophers, and J.-M. Schröder, Nature 387, 861
Materials at Risø National Laboratory in Denmark.
(1997).
36) J. Harder and J.-M. Schröder, J. Biol. Chem. 277, 46779 (2002). He is now professor and section head of New Light
37) R. Gläser, J. Harder, H. Lange, J. Bartels, E. Christophers, and Sources and Industrial Sensors at in the department
J.-M. Schröder, Nat. Immunol. 6, 57 (2005). of photonics engineering at the Technical University of Denmark.

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