A novel LED irradiation system developed by the Ferdinand-Braun-Institut aims to kill microorganisms with ultra-shortwave UV light – without side effects. Dr Sven Einfeldt talks to HEQ about its potential implications.
According to the World Health Organization hospital-associated infections (HAI) affect hundreds of millions of patients worldwide every year, leading to large numbers of deaths and having a significant economic impact on health systems. Multi-drug resistant (MDR) pathogens are the cause of many of these infections, which do not respond to existing antimicrobial treatments such as antibiotics. Researchers across the globe are working to find alternative approaches to tackling MDR pathogens and UVC light has been proven to successfully destroy microorganisms without allowing resistances to develop.
Within the framework of their Joint Lab GaN Optoelectronics, the Ferdinand-Braun-Institut and Technische Universität Berlin have developed LEDs emitting in the far-ultraviolet (UV) spectral range. Their light does not penetrate into the living layers of the skin because of their high degree of absorption and while tests are ongoing it is anticipated that their use will not damage or put any strain on the skin, in contrast to the use of longwave UVC radiation.
The first prototype was delivered to the Department of Dermatology at Charité – Universitätsmedizin Berlin, which will be conducting dose-dependent investigations of possible DNA damage to irradiated skin. A second device is being tested for microbicidal effectiveness at the Institute for Hygiene and Environmental Medicine of the University Medicine Center Greifswald. The tests will determine how effectively the UV LED emitters kill MDR pathogens at 233nm and compare the results with those of UV lamps with emission at 254nm and 222nm.
LEDs are particularly small and can be used to create miniaturised irradiation systems, which bring many benefits and could be used endoscopically in body orifices or as handheld devices.
Dr Sven Einfeldt, of the Joint Lab GaN Optoelectronics at the Ferdinand-Braun-Institut, spoke to HEQ about the drivers for creating the system and its potential implications.
How much of an issue are hospital-associated infections? Why are they so difficult to prevent?
I’m a physicist, so I can only cite our co-operation partners working in the field of medicine, but they tell us all the time how big of an issue that is. Not only in hospitals, but generally in infections with multi-drug resistant organisms.
The Robert Koch Institute in Berlin, Germany, says there are 400,000 to 600,000 infections with these hospital germs every year in Germany, and about 10,000 to 20,000 people die from them. If you consider the situation worldwide, about 700,000 are expected to die every year from these infections. That is a huge number and the trend is rising.
Our partners told us that some estimations say that in the year 2050 about 10 million people will die from these multi-drug resistant organisms worldwide. That is actually going to be larger than the number of people dying from cancer in the year 2050. How realistic that expectation is I don’t know, but we are talking about large numbers.
The main reason why HAIs are difficult to prevent is that in hospitals, there are many patients with wounds where the pathogens can attack, but we also use a lot of antibiotics in hospitals; and while these help in the short term, in the long term this promotes organisms that are resistant. The problem becomes more significant over time because these resistant microorganisms are then hard to combat with antibiotics.
What were the main drivers for you developing the LED irradiation system? What were your ultimate aims and objectives?
I am at the Ferdinand-Braun-Institut and we are working closely with the Technische Universität Berlin, and we have both been developing LEDs emitting in the ultraviolet spectrum range for many years. Initially, we were developing LEDs in the UVB range and near-UVC range: these are longer wavelength UV LEDs, because we were considering applications like curing of materials, or treating skin diseases, or disinfecting drinking water. But we began asking ourselves just from a critical or technological point of view, can we go much, much shorter in the wavelength? What is the shortest wavelength we can achieve with an LED? Can we go to the far-UVC range? And we started to develop these LEDs.
One of our current partners from the medical field contacted us and told us about some very recent developments in the USA, where a group started to use far-UVC light to inactivate microorganisms, and they observed that this particular far-UVC light caused very little damage to the skin. They were using lamps, but we thought that we could also do it with LEDs and we started to investigate that because we were convinced that LED is a better far-UVC light source than a lamp at least in certain respects. So, that was the starting point for moving into this area. Can we use far-UVC radiation to inactivate and remove microorganisms without harming the skin when we apply this radiation directly on living beings?
The prototype has been developed within the framework of the VIMRE project. Can you tell me more about the aims/objectives of the project and how it fits within the Twenty20 programme?
Twenty20 is a programme from the German Ministry of Education and Research, which is aimed at supporting larger consortia consisting of universities, research institutes and companies, working together on specific topics. The idea is to expand economic and scientific competencies in a certain area.
We are working within the framework of the VIMRE project (prevention of infection with multi-drug resistant pathogens via in vivo UVC irradiation), and that is part of a consortium called Advanced UV for Life, which was established in 2012, and brings together just under 50 institutions in Germany, who are working on developing UV LEDs and applying them in different ways. This consortium covers the whole value chain so there are people like us who are developing LEDs and other institutions working on using these LEDs in medicine, the environment and life sciences, for example.
The VIMRE project is part of the field of medicine which deals with using LEDs to treat skin diseases such as psoriasis to measure the sun protection factor of creams directly on the skin, and again it covers the whole value chain.
We are working on the LED side and then our partners in the medical field apply that. We deliver prototypes and they use them for experiments on microorganisms and the skin.
How does your LED irradiation system work and what makes it different to other systems? What are the benefits of the system?
The system is made out of 120 LEDs and each of these LEDs emits at a wavelength of 233nm, which is a very, very short wavelength for an LED. We are at the very edge of the development of UV LEDs, as these short wavelengths are not available on the market worldwide, there is just one company which provides some research samples.
These 120 LEDs in our system are packed very closely together and the system is designed to illuminate an area of about 10cm by 10cm very efficiently and as uniformly as possible. So, we have implemented optical reflectors both on the LED level and on the whole system level to make the radiation pattern very uniform. We have also implemented optical filters, because we know that we want to focus on very short wavelength radiation, and we want to filter out all the long wavelength radiation because that is potentially harmful for the skin. So, we filter out almost all the radiation for wavelengths larger than 240nm.
As far as I know, this is the only far-UVC irradiation system worldwide that consists of LEDs, as all the other systems available worldwide are using lamps. To be honest, lamps have advantages and one of the biggest advantages compared to our LEDs is that they are more efficient.
However, we are convinced that we are only at the beginning of the development of these LEDs. We hope to increase their performance in the near future and are confident that the LEDs will show their true advantages compared to lamps. They’re much smaller and more compact and they’re not fragile so you are more flexible in building irradiation systems that are an optimal fit for a human body, or which can even be implemented into body cavities, and medical people tell us that is what is needed.
We are currently performing experiments to compare the two approaches, with both LEDs and lamps, so it’s a little bit too early to say which one is better. For us, this is not the most important thing right now and we will be extremely happy, if we can show that the system is at least as good as the lamp systems are in terms of killing microorganisms while only damaging the skin as little as possible. Because if we can show that then we are convinced that a long-term LED technology will become widely accepted because it has so many advantages. If, in the end, we want to apply it in an antisepsis context to humans, then we need to be able to build systems that fit to the human body and I think our LEDs have many advantages compared to lamps.
The biggest challenge we have is improving the performance of the LEDs, while also improving their reliability because right now they are rather inefficient. But we are optimistic because if you look back 20 years or so when blue LEDs or white LEDs started, they also started as very inefficient light sources and now they are the most efficient way to illuminate rooms. We hope to also follow this path with our far-UVC LEDs.
If our system is able to help with the situation with multi-drug resistant organisms at hospitals, which are really hard to combat, that would be very, very interesting.
The first prototype was delivered to the Department of Dermatology at Charité for skin examinations. What kind of tests will be carried out and what is the expected outcome?
The Charité in Berlin is currently using our LED irradiation system to irradiate samples of porcine and human skin. They look for possible skin damage, through analysing the DNA and cells of the skin. We know already what dose we have to apply in order to inactivate certain multi-resistant organisms, such as MRSA and the tests at Charité have shown that only very minor DNA damage is induced. They have only seen a small amount of damage to the very top layers of the skin and the deeper parts of the skin remain intact. So, from that point of view, it seems to be not damaging the skin considerably. Also keeping in mind that the skin has the capability of repairing itself within a day or two if the damage is not too significant.
So far, the doses used in the tests at Charité have damaged the skin at a similar level to five to 10 minutes in the midday sun.
We are still at the beginning with the tests and there are many things to investigate like different skin types, for instance, different ages of skin or different colours of skin. But the early experiments show that principally the concept seems to work.
What kind of tests will be carried out on the second device at the Institute for Hygiene and Environmental Medicine of the University Medicine Center Greifswald? What is the expected outcome of these tests?
They are investigating the impact of this far-UVC LED radiation on microorganisms. They pick certain microorganisms and irradiate those in order to find out what effect the radiation has on them. They have started with MRSA and discovered that the dose needed to inactivate this microorganism with our LED system is 40 millijoules/square centimetre.
They are now in the second phase, trying to investigate whether the inactivation depends on the medium where the microorganisms are embedded. So, if they are on the skin, microorganisms are not on a pure surface, but they are embedded in some other substance such as, proteins, this may change the impact of the far-UVC LED light on these microorganisms.
Once testing is complete what kind of applications will the device be used in and what impact will it have?
I think maybe in the not-too-distant future far-UVC irradiation systems with LEDs could perhaps be used to reduce the danger posed by multi-drug resistant pathogens in hospitals. For instance, particularly by irradiating certain regions of the human body or irradiating open wounds during surgery.
Also, it would be not too unrealistic to consider irradiating the inside of the nose, which our medical partners tell us is known to be a region colonised by certain multi-drug resistant organisms. The nose is very often the starting point in the body for an infection caused by one of these microorganisms. So, one could think about illuminating very, very particular areas on the human body, which are known to be the source of infections. And at this point, of course, LED would be ideally suited to do things like that.
On the other hand, one has to be very careful. These are still very ambitious goals, and you want to be really sure that you are not doing more harm than good. There are still a lot of things to investigate, such as the effects on the skin and we also have to consider the legal framework for doing this. Right now you would not be allowed to apply such radiation to the human body in a dose that actually removes or sufficiently inactivates these microorganisms. So, we’re still at the phase where we are trying on a scientific level to find out whether that is really a good way to go, and then, of course, internally, we would need to work on the framework that would allow us to do this at some point on humans.
Could the device be used to stop the transmission of COVID-19?
So far, most of the time we have just considered multi-resistant bacteria, but far-UVC irradiation and general UVC radiation can also inactivate viruses. It is already known that COVID-19 is a virus that can be inactivated by UVC light. Interestingly, it’s pretty sensitive to UVC lights, so you only need very small doses to inactivate that if you compare it to other certain kinds of bacteria.
The question is, where do you want to use the UVC radiation system that you’re building in order to combat COVID-19? Because, if for instance, you want to use it in contexts where humans cannot be exposed to the UVC radiation, there is no real need to go to very small wavelengths.
However, there are also people who have a vision to use far-UVC LEDs to illuminate complete rooms, while there are people in the rooms, with the argument, that it does not harm people.
This is very much looking the future, so I’m not sure how realistic that is but it’s an interesting way to think. Of course, you would need really efficient far-UVC sources and a lot of power for the LEDs, or lamps. You would also need to be very sure that you do not harm anything, which has been exposed to this light. It is still very far in the future, but it is something which is becoming more and more realistic.
Dr Sven Einfeldt