Interview of Prof. Sei Kwang Hahn, The world’s first lens for diabetes diagnosis and drug delivery
A domestic research team developed a lens that relieves diabetic patients of the inconvenience of drawing blood and measuring blood sugar every day. The lens is said to measure blood sugar in real-time and automatically administer drug. Let us look into how it was developed. We’re going to connect to Prof. Sei Kwang Hahn of POSTECH Department of Materials Science and Engineering. Hello, Prof. Hahn?
I heard you developed a smart contact lens that is capable of measuring blood sugar and delivering drug for diabetic patients. Could you tell us how it was developed?
I conceived the basic concept for developing smart contact lens while I was spending the research year at Harvard Medical School in 2012. People say the eyes are the window of the mind, but they actually reflect the conditions of the body’s organs better than anything. For example, when you are tired, your eyes grow bloodshot, and if you get jaundice, your eyes turn yellow.
It is recently reported that an unhealthy liver shows its sign in the eyes. Taking into account these known facts about the eyes, I began to develop a smart contact lens. Later, with Prof. Jae-Yoon Sim of POSTECH Department of Electrical Engineering and Prof. Keon Jae Lee of KAIST Department of Materials Science and Engineering, and the support of the Samsung Science & Technology Foundation, we have secured the necessary technologies and registered related domestic and overseas patents, and launched into the full-fledged development of the product.
What do you think is the importance of this new invention?
Recent reports in the press showed that Google’s biotech company plans to launch a bio-business that provides diabetes diagnosis through the measurement of blood sugar in tears in collaboration with the international pharmaceutical giant Novartis. As such, scores of researchers have dedicated their efforts to developing smart lens that can measure blood sugar in tears, but our team is the first one in the world that developed a smart lens to both diagnose and treat diabetes by analyzing blood sugar levels in tears.
You have just mentioned that a blood sugar-measuring contact lens is under development also outside Korea. How is it different from the kind you have developed?
Google’s lens is also a kind of smart lens that estimates blood sugar contained in tears, so on the conceptual level, it is not different from ours. But the biosensor of the lens we devised is equipped with three platinum electrodes and has a significantly enhanced sensitivity, enabling more accurate and precise blood-sugar measurement. What’s more, we observed that the repeated use of the biosensor over two weeks didn’t diminish the accuracy of the blood-sugar measurement.
I heard the lens includes a drug delivery system in it. How does this drug delivery system work?
As you have just said, this smart lens is equipped with a drug delivery system and able to administer drug into the eyes depending on the measurement of the biosensor. We filled eight 30 nL-sized storages with highly concentrated drug and coated them with a golden film to create a drug delivery system. When you run electric current through the system wirelessly, the drug gets released as the golden film melts. I expect that the lens could be effective to treat a range of eye diseases including diabetic retinal disease and glaucoma and corneal neovascularization.
You said that it could be effective to treat various eye diseases. What else could we benefit from this smart lens?
As we know, the eyes can be the optimum interface connecting a variety of electronic devices with the body. Our smart lens can not only monitor many diseases in real-time and effectively, but also administer drug into the eyes depending on the diagnosis. This is a theranostic system that enables diagnosis and treatment at once. Furthermore, the technologies behind the smart contact lens are expected to help commercialize various medical wearable devices such as artificial lens and electronic skin.
Diabetic patients have to draw blood and measure blood sugar every day and that is such an inconvenience for them. So I think it will be great if this lens comes to market as soon as possible. When do you think its commercialization will happen?
We have finished proof-of-concept on the functions of the smart lens. For full-scale commercialization, we have been meeting with a number of companies including Johnson & Johnson, VisionCare, and Genexine to discuss about joint product development. The simple biosensor-equipped smart lens like the one developed by Google seems to need three more years until commercialization, and the drug delivery system-equipped smart lens for both diagnosis and treatments is considered to need at least five years of research including clinical trial.
We are curious about your follow-up research.
I’m working on multiple follow-up research projects. The first one is the collaboration with Prof. Per-Olof Berggren, a member of the Nobel Assembly at Karolinska Institute, to seek diabetes treatment using pancreatic cells and a smart lens. When pancreatic cells are implanted in the eyes, they produce and release insulin into the body, so we are jointly studying how to detect blood sugar levels in tears and control the pancreatic cells using a smart lens.
The second one is the joint efforts with Prof. Chun Ki Joo of The Catholic University of Korea School of Medicine to develop an eye disease treatment system that uses light through an LED-equipped smart lens. And I’m planning to research how to coat the surface of a smart lens with picture elements and materialize virtual reality. This is the future technology that appeared in the recent Mission Impossible movie starring Tom Cruise. With this new smart lens we developed, I hope we could significantly contribute to the advancement and commercialization of ICT converging technologies. Thank you so much for giving me a chance to introduce our smart lens and research achievement.
We have talked about the smart lens that enables daily blood sugar measurement and automatic drug release. He was Prof. Sei Kwang Hahn of POSTECH Department of Materials Science and Engineering. Thank you for the interview.
“Measuring blood sugar through tears”
“The sensor measures blood sugar, sends information to the chip, and signal drug release.”
“A blood sugar-measuring lens takes three years, and a drug-delivering one, another five years until commercialization”
Diabetic patients draw blood on the tip of their finger to measure blood sugar every day. Soon, such inconvenience is expected to disappear. It is thanks to the ‘smart’ contact lens that can measure blood sugar in real-time and automatically release drug. The International Diabetes Federation predicted that one in every ten people will be diabetic by 2035. And the competition between contact lens manufacturers is getting fiercer to secure the new medical technologies in advance.
◇ From blood sugar measurement to drug release
The science and engineering news site IEEE Spectrum reported that Prof. Sei Kwang Han in the department of Materials Science and Engineering of POSTECH developed a smart contact lens that helps diabetic patients with damaged retina measure blood sugar and administer drug. The smart contact lens was made by putting an electronic circuit between two soft lenses. The heart of the technology is the blood sugar-measuring sensor.
Like blood, tears contain a type of sugar called glucose. It is known that the blood sugar level in the body is proportionate to the sugar level in tears. In other words, the blood sugar level can be figured by measuring sugar in tears. When sugar in tears combines with glycolytic enzymes attached to the sensor, hydrogen peroxide is produced. Hydrogen peroxide, in turn, puts out atoms in the process of being splitting into hydrogen and oxygen. So there flows more electric current. If you detect the flowing of the current, you can figure out the sugar level. The higher the sugar level, the higher the electric current.
A blood sugar estimate is sent from the sensor to the microprocessor chip. If the measurement exceeds a certain level, the chip signals to release drug. Right next to the chip are ten microscopic drug containers. A signal coming from the chip prompts electric current, and it melts the golden film barring the opening of the drug container. Subsequently, the drug trickles out into the eye. Prof. Sei Kwang Hahn said, “Since a patient needs to take antidiabetic drug once every three days, a contact lens can be used for a month.”
The coil built in the contact lens sends out the information collected by the sensor and receives electrical signals. The POSTECH research team expects the blood sugar-measuring-only lens will need three years, and the one with a drug-delivery system will take five years until the commercialization. The research team has entered into discussion for joint product development with the American pharmaceutical company Johnson & Johnson.
◇ Lens for glaucoma patients on the market
▲ Tonometry lens – Wearing ‘Triggerfish,’ the lens for glaucoma patients produced by the Swiss company Sensimed. The tonometry sensor built in the lens measures the intraocular pressure on a regular basis. (Image courtesy of Sensimed)
This is not the first time that a diagnostic contact lens has been developed. Google is also developing a blood sugar-measuring smart contact lens. Its test product released in 2014 includes a ring-shaped coil, microscopic sensor, and chip. Google is working in collaboration with the Swiss pharmaceutical company Novartis, which is also a contact lens manufacturer. Google’s blood sugar-measuring sensor has been known to also use glycolytic enzymes. Dr. Yong-won Song of the Korea Institute of Science and Technology, and Prof. Jaheon Kang of ophthalmology at the Kyung Hee University Hospital at Gangdong, too, succeeded in developing a tear glucose-detecting sensor and embedding it into a contact lens in 2014.
There is already a diagnostic contact lens on the market. ‘Triggerfish’ of the Swiss company Sensimed for glaucoma patients, after coming on the European market, was licensed to be sold in the United States in March. The two biggest threats to the loss of eyesight are glaucoma and diabetic retinal disease. Glaucoma raises the intraocular pressure and leads to the optic nerve damage, so glaucoma patients have to frequently check the intraocular pressure. The Triggerfish contact lens contains a tonometry sensor. As the tonometry gauge goes up, the cornea puts pressures on the contact lens. As a result, the sensor inside the lens changes shape and measures the intraocular pressure.
The current technology trend is the merge of diagnosis and drug delivery. Prof. Ali Yetisen of University of Cambridge predicted that medical contact lenses will not stop with diagnosis, but evolve to include the drug-delivery function in his paper published in the international academic journal Advanced Healthcare Materials.
“The evolution of medical adhesives”
A state-of-the-art medical adhesive is making medical history. It is easy to use and you can even take a shower a day after use. As the adhesive that can be applied not only on the skin but also onto the internal organs and bones has recently been developed, the medical adhesive technologies are advancing at a rapid pace.
◇ Maintain strong adhesion even to blood-pumping heart
An American research team developed an adhesive that turns into solid in contact with light and succeeded in closing a cut on the cardiac wall using the adhesive. (Image courtesy of The Karp Lab)
Last year, an American weekly news magazine Time named Maria Pereira, a 31-year-old Portuguese medical scientist, as one of the next generation leaders and predicted that the adhesive of her invention available everywhere on the body will bring about a revolution in the medicine.
She began her research to figure out the safe way to suture the surgical incision in the hearts of babies with congenital heart defect. The medical adhesive approved by FDA in 1998 was effective on skin cuts, but hard to be applied to internal organs like the heart. Once the skin healed, you could simply peel off the adhesive, but when applied onto the internal tissue, it required the extra removal process. Fibrin glue, based on hemostatic agent, was also available, but its adhesion was weak and it took a long time to take effect.
Dr. Pereira in cooperation with Prof. Jeffrey Karp of Harvard Medical School developed a liquid adhesive that turns into solid in contact with light (HLAA: hydrophobic light-activated adhesive) and reported the achievement in Science Translational Medicine in 2014. Also, Yuhan Lee, a Korean post-doctorate researcher, participated in the research as a member of Prof. Karp’s team.
When the research team applied the adhesive on the surgical incision in the heart and flashed light, it turned into elastic solid and closed the incision. Even in the environment where blood kept flowing and high blood pressure was applied, the adhesive strength was retained. Most importantly, the adhesive biodegrades after a wound gets healed. It also proved effective in heart surgery on rats and pigs. Gecko Biomedical where Dr. Pereira is the chief researcher plans to roll out the medical adhesive this year at the soonest.
A similar research is in progress in Korea. The joint research team led by Prof. Sei Kwang Hahn of POSTECH Department of Materials Science and Engineering and Prof. Seok Hyun Yun of Harvard Medical School developed a technology to stick skin tissues together using light. When a light-sensitive material was applied on a wound and light was flashed on it, collagen in the skin agglomerated and the would was closed. The waveguide that delivers light biodegrades, so the adhesive can be used deep in the skin. The researchers was successful in animal testing on the pig’s skin and published the result in Advanced Functional Materials on February 1.
◇ Bone adhesive made out of mussel
Two weeks’ recovery after applying the adhesive made out of mussel’s adhesive protein (Right): The recovery was faster and the scar was smaller than when suture threads or conventional adhesives were used. (Image courtesy of POSTECH)
A medical bone adhesive is also going to be rolled out. The marine molecular biotechnology laboratory led by Prof. Hyung Joon Cha of POSTECH Department of Chemical Engineering used mussel’s adhesive protein clinging to rocks and developed a medical adhesive that helps bone regeneration.
When a bone is broken, it is fixed in place with pins, but when a bone gets broken into small pieces, bone graft material made of cow or pig’s bone powder is filled in to help the bone regenerate. The problem is that the bone fillings might scatter about. For dental implant surgery, graft material can be used to support the bone, but the moist in the mouth interferes the grafting process.
The research team in collaboration with Prof. Sang-ho Jun of dentistry at the Korea University Anam Hospital found a method to fix graft material with the adhesive made from mussel’s glue protein. When the researchers made a hole on a rat’s skull and applied the new method, the bone growth factors readily adhered to the graft material and bone regeneration gained speed by 1.5 times. The research outcome was published in Journal of Materials Chemistry B in 2014.
Prof. Cha‘s team also succeeded in gluing skin tissues by applying mussel’s glue protein and blue light. Seven days after the method was applied on a rat’s wound, it was closed and the adhesive completely biogenerated. Two weeks later, the scar was hardly visible. The result was published in Biomaterials last year.
Prof. Cha said, “Unlike other medical adhesives out of artificially synthesized chemicals, this adhesive coming from natural mussel glue is safe for the human body. At the earliest, we’ll start the clinical trial this year and the product will come on the market late next year.”
Prof. Jung Ho Je’s team of POSTECH Department of Materials Science and Engineering developed a ‘cell endoscopy’ technology for the first time that interacts with living neuronal cells through light and measures the amount of copper ions. The exact quantity of copper ions required in cells has not been known, but Prof. Je’s team measured the quantity of copper ions in the neurons of the cerebral cortex and hippocampus and reported the achievement in the prestigious Advanced Materials. The new technology draws attention from academic communities as it opens a possibility of solving the mystery of memory formation as well as early diagnosis of degenerative mental illnesses including Alzheimer’s disease. Copper ions are the moderator of the nervous system, and their distribution across neurons and their optimum amount need to be figured out for early diagnosis of Alzheimer’s disease and other degenerative neuronal diseases. However, the conventional methods couldn’t measure copper ions exclusively, or get accurate estimates, barring quantitative analysis, and depending on method, only frozen cells were applicable or cells could get contaminated with toxic substance. So the research team developed a nanowire probe that reacts with copper ions and then changes the fluorescence of light. Since the nanowire probe allows light and cells to directly exchange microscopic optic signals, fluorescent material didn’t have to be put into the cells and the quantity of copper ions in neurons was successfully measured with minimized absorption and scattering of light.
This research is expected to advance the technology for early diagnosis and treatment of degenerative mental disorders, as well as bio-information monitoring and nano-sized biosensors. Especially, since copper ions are known to involve in forming memories in the brain, this research is expected to help figure out the workings of the brain.
Quantitative Probing of Cu2+ Ions Naturally Present in Single Living Cells
A drone is a unmanned small aircraft that can be used with simple operation for aerial photo shoot, disaster response, and many other purposes, and a new route has been opened up to extend a drone’s flight time from 20 minutes to over an hour. Since drones are easy to operate and carry around, the drone market has been rapidly growing, but the biggest weakness is that the battery capacity is too small and limits the length of flights to less than an hour. Against the backdrop, a POSTECH research team developed a fuel cell that could address the disadvantage of drones. According to POSTECH, Prof. Gyeong Man Choi and Kun Joong Kim in PhD-MS integrated program of Department of Materials Science and Engineering have succeeded in developing a small SOFC (solid oxide fuel cell) that can replace lithium battery in micro-electronic devices such as smartphones, laptops and drones, and published their achievement in the March issue of Scientific Reports, affiliated with Nature. Especially, the small SOFC of the team’s invention is expected to be used also for high-capacity fuel cells available for cars. Also known as the third-generation fuel cells, SOFCs have a relatively simple structure and cause no electrolyte loss or erosion issues as solid oxides are used as electrolyte. That is why many researchers have been studying this kind of fuel cells. However, the conventional silicon support structure for small SOFCs is likely to go through sudden deterioration due to unaligned thermal expansion with electrolyte while oxygen ions move from electrolyte to the anode and reacts with hydrogen from the cathode to produce electric current, and its low durability, too, prevented SOFCs from being put to practical use. To solve the problem, the research team created the world’s first technology to enhance both the performance and durability of SOFCs by building them on a porous support structure in stainless, which endures thermal or mechanical stress and oxidation-reduction reaction, and by coating the support structure with a thin film of minimized thermal capacity. The substrate in use was produced through the tape casting-compression-sintering process so that it could respond to enlargement and mass production. Because this SOFC shows high power density even at 550 Celsius degree, it is suitable to portable electronics like smartphones, laptops, and drones that require high-speed operation and high performance at the same time. Also, since it is cheap, it has opened a way to develop large-sized fuel cells for next-generation electric cars. Prof. Choi said, “Thanks to this fuel cell, we could see a drone flying for over an hour and a smartphone that you need to charge only once a week.”
Prof. Sei Kwang Hahn of POSTECH Department of Materials Science and Engineering and Prof. Seok Hyun Yun of Harvard Medical School announced on the 2nd that their joint research team have developed a photomedicinal technology in which light enables vaccine to be absorbed on the skin without injection. Photomedicine is a new field of medicine that makes use of light such as lasers for medical treatments including dermatologic procedures, anticancer treatment, plastic surgery and so on. The research team has found a way to build up immunity by applying hyaluronic acid-mixed vaccine on the skin and casting light on the spot. It was possible because hyaluronic acids, the biopolymer material, readily permeate through skin. As a vaccine is applied and absorbed on the skin, the researchers explained, the risk of infection from injection can be minimized and the convenience of the patients be improved. Also, the team created a technology to heal and regenerate skin tissues by applying photosensitive dye on the scar and providing light through biopolymer waveguide. The technology uses light and brings about the ‘bridging reaction’ of collagen within the tissue, and the optical waveguide in use biodegrades in the body and doesn’t need to be removed. Prof. Hahn said, “We’ll strive to advance a variety of photomedicinal technologies in continuous collaboration with Harvard Medical School.” The research outcome was published in Advanced Functional Materials, the prestigious materials science journal, and Nature Communications, the extensive global scientific journal.
In an SF movie scene, you get ready to go out and put on your shoes at the door, and then your car automatically pulls in front of you and brings you to your destination. Could the scene actually happen in real life?
A POSTECH research team developed a semiconductor device in a simple structure that imitates the supercomputer-like human brain, and the new invention is expected to be applied to a variety of uses, such as brain signal-using control systems or smart robots. The modern machinery including computers conducts standardized works like mathematical calculations rapidly and accurately, but it is highly inferior to humans when it comes to perceiving the environment and drawing information in unexpected situations. This is due to the digital system that conducts a single order at a time and repeats it at a high speed while memory and processer are separated. In short, it is not able to adequately respond to changes while processing complex and unstandardized information at once. On the other hand, in the human brain, over 100 billion neurons exchange signals with each other through the link called synapse, and they work simultaneously to process, store, and retrieve information in no time. That is why a neuromorphic system that imitates the human brain comes under the spotlight as the next-generation technology, but the existing design needs more transistors, larger semiconductor chips, and higher electricity consumption, making it difficult to be practical. However, Prof. Hyun Sang Hwang’s team of POSTECH Department of Materials Science and Engineering developed a microscopic, ultra-energy-efficient neuromorphic device that functions like a synapse and neuron of the brain and enables parallel data process and learning. The researchers created a neuron-like device with NbO2, a nonconductor convertible into metal, and put in PCMO, a conducting oxide, to serve as a synapse. The simple structure was made to memorize changing values at regular electrical stimulations and operate exclusively under certain conditions so that the single device can work as much as dozens of transistors do. Also, the team found that even when the size of the device was reduced to nanometers, the performance didn’t change, which means the team could replicate the high density of finely intertwined synapses and neurons in the human brain. The research outcome was presented at the IEEE International Electron Devices Meeting, the prestigious academic conference in the field of semiconductor technologies recently held in the United States, and garnered interest from the academic community. Prof. Hwang said, “Our team will go further to develop more technologies like pattern-recognition based on this achievement. Once we can analyze brain, video, and image signals in real-time, the new technology could be applied to a variety of things including brain signal-detecting driverless vehicles.”
A POSTECH research team developed a technology that utilizes melanoidins, the substance that makes coffee-roasting aromatic, into photoacoustic medical imaging, anticancer treatment, liposuction, and plastic surgery. Prof. Sei Kwang Hahn of POSTECH Department of Materials Science and Engineering launched a joint research project with Prof. Chulhong Kim of POSTECH Department of Creative IT Engineering and Dr. Min-young Lee of Samsung Advanced Institute of Technology, and the research team succeeded in synthesizing a biodegradable, photoacoustic melanoidin and developing a novel photoacoustic and photothermal treatment technology. The achievement was published in the online issue of ACS Nano, a world-renowned academic journal on nanoscience and nanotechnology. Melanoidins are formed from the Maillard reaction of amino acids and sugar and in the course of food processing or preservation, and they are known as antioxidant and anticancer substance. The researchers discovered for the first time that melanoidins have the photoacoustic property of producing sound waves upon being exposed to light, and using melanoidins, succeeded in taking medical images of lymphatic glands and internal organs involved in cancer metastasis. Also, the team used the fact that melanoidins, having the photothermal property, produce heat upon receiving light, and succeeded in killing heat-vulnerable cancer tissues and dissolving fat. As biopolymers harmless to the human body, melanoidins biodegrade and get discharged out of the body after being used for medical imaging, and so the academic communities are expecting them to eliminate risks from using contrast medium for X-ray or MRI scans. In addition to photothermal treatment, the melanoidin-using technology is expected to be effective for liposuction as it can remove fat tissues without incision, minimizing risks from surgical procedures. Prof. Sei Kwang Hahn who led the research said, “With this research, we saw for the first time the possibility to use melanoidins for effective medical imaging and photothermal treatment. I will keep working toward the commercialization of new photomedicine technologies.”
The research was funded by the National Research Foundation of Korea, and Prof. Hahn’s team has been actively conducting research to develop biomaterials for nanomedicine. He also received the Presidential Award at the 2015 Korea Invention Patent Exhibition for his technological achievement.