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KAIST Team Develops Highly-Sensitive Wearable Piezoelectric Blood Pressure Sensor for Continuous Health Monitoring
- A collaborative research team led by KAIST Professor Keon Jae Lee verifies the accuracy of the highly-sensitive sensor through clinical trials
- Commercialization of the watch and patch-type sensor is in progress
A KAIST research team led by Professor Keon Jae Lee from the Department of Materials Science and Engineering and the College of Medicine of the Catholic University of Korea has developed a highly sensitive, wearable piezoelectric blood pressure sensor.
Blood pressure is a critical indicator for assessing general health and predicting stroke or heart failure. In particular, cardiovascular disease is the leading cause of global death, therefore, periodic measurement of blood pressure is crucial for personal healthcare.
Recently, there has been a growing interest in healthcare devices for continuous blood pressure monitoring. Although smart watches using LED-based photoplethysmography (PPG) technology have been on market, these devices have been limited by the accuracy constraints of optical sensors, making it hard to meet the international standards of automatic sphygmomanometers.
Professor Lee’s team has developed the wearable piezoelectric blood pressure sensor by transferring a highly sensitive, inorganic piezoelectric membrane from bulk sapphire substrates to flexible substrates. Ultrathin piezoelectric sensors with a thickness of several micrometers (one hundredth of the human hair) exhibit conformal contact with the skin to successfully collect accurate blood pressure from the subtle pulsation of the blood vessels.
Clinical trial at the St. Mary’s Hospital of the Catholic University validated the accuracy of blood pressure sensor at par with international standard with errors within ±5 mmHg and a standard deviation under 8 mmHg for both systolic and diastolic blood pressure. In addition, the research team successfully embedded the sensor on a watch-type product to enable continuous monitoring of blood pressure.
Prof. Keon Jae Lee said, “Major target of our healthcare devices is hypertensive patients for their daily medical check-up. We plan to develop a comfortable patch-type sensor to monitor blood pressure during sleep and have a start-up company commercialize these watch and patch-type products soon.”
This result titled “Clinical validation of wearable piezoelectric blood pressure sensor for health monitoring” was published in the online issue of Advanced Materials on March 24th, 2023. (DOI: 10.1002/adma.202301627)
Figure 1. Schematic illustration of the overall concept for a wearable piezoelectric blood pressure sensor (WPBPS).
Figure 2. Wearable piezoelectric blood pressure sensor (WPBPS) mounted on a watch (a) Schematic design of the WPBPS-embedded wristwatch. (b) Block diagram of the wireless communication circuit, which filters, amplifies, and transmits wireless data to portable devices. (c) Pulse waveforms transmitted from the wristwatch to the portable device by the wireless communication circuit. The inset shows a photograph of monitoring a user’s beat-to-beat pulses and their corresponding BP values in real time using the developed WPBPS-mounted wristwatch.
2023.04.17 View 5155 -
A biohybrid system to extract 20 times more bioplastic from CO2 developed by KAIST researchers
As the issues surrounding global climate change intensify, more attention and determined efforts are required to re-grasp the issue as a state of “crisis” and respond to it properly. Among the various methods of recycling CO2, the electrochemical CO2 conversion technology is a technology that can convert CO2 into useful chemical substances using electrical energy. Since it is easy to operate facilities and can use the electricity from renewable sources like the solar cells or the wind power, it has received a lot of attention as an eco-friendly technology can contribute to reducing greenhouse gases and achieve carbon neutrality.
KAIST (President Kwang Hyung Lee) announced on the 30th that the joint research team led by Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering succeeded in developing a technology that produces bioplastics from CO2 with high efficiency by developing a hybrid system that interlinked the electrochemical CO2 conversion and microbial bio conversion methods together. The results of the research, which showed the world's highest productivity by more than 20 times compared to similar systems, were published online on March 27th in the "Proceedings of the National Academy of Sciences (PNAS)".
※ Paper title: Biohybrid CO2 electrolysis for the direct synthesis of polyesters from CO2
※ Author information: Jinkyu Lim (currently at Stanford Linear Accelerator Center, co-first author), So Young Choi (KAIST, co-first author), Jae Won Lee (KAIST, co-first author), Hyunjoo Lee (KAIST, corresponding author), Sang Yup Lee (KAIST, corresponding author)
For the efficient conversion of CO2, high-efficiency electrode catalysts and systems are actively being developed. As conversion products, only compounds containing one or up to three carbon atoms are produced on a limited basis. Compounds of one carbon, such as CO, formic acid, and ethylene, are produced with relatively high efficiency. Liquid compounds of several carbons, such as ethanol, acetic acid, and propanol, can also be produced by these systems, but due to the nature of the chemical reaction that requires more electrons, there are limitations involving the conversion efficiency and the product selection.
Accordingly, a joint research team led by Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST developed a technology to produce bioplastics from CO2 by linking electrochemical conversion technology with bioconversion method that uses microorganisms.
This electrochemical-bio hybrid system is in the form of having an electrolyzer, in which electrochemical conversion reactions occur, connected to a fermenter, in which microorganisms are cultured. When CO2 is converted to formic acid in the electrolyzer, and it is fed into the fermenter in which the microbes like the Cupriavidus necator, in this case, consumes the carbon source to produce polyhydroxyalkanoate (PHA), a microbial-derived bioplastic.
According to the research results of the existing hybrid concepts, there was a disadvantage of having low productivity or stopping at a non-continuous process due to problems of low efficiency of the electrolysis and irregular results arising from the culturing conditions of the microbes.
In order to overcome these problems, the joint research team made formic acid with a gas diffusion electrode using gaseous CO2. In addition, the team developed a 'physiologically compatible catholyte' that can be used as a culture medium for microorganisms as well as an electrolyte that allows the electrolysis to occur sufficiently without inhibiting the growth of microorganisms, without having to have a additional separation and purification process, which allowed the acide to be supplied directly to microorganisms.
Through this, the electrolyte solution containing formic acid made from CO2 enters the fermentation tank, is used for microbial culture, and enters the electrolyzer to be circulated, maximizing the utilization of the electrolyte solution and remaining formic acid. In addition, a filter was installed to ensure that only the electrolyte solution with any and all microorganisms that can affect the electrosis filtered out is supplied back to the electrolyzer, and that the microorganisms exist only in the fermenter, designing the two system to work well together with utmost efficiency.
Through the developed hybrid system, the produced bioplastic, poly-3-hydroxybutyrate (PHB), of up to 83% of the cell dry weight was produced from CO2, which produced 1.38g of PHB from a 4 cm2 electrode, which is the world's first gram(g) level production and is more than 20 times more productive than previous research. In addition, the hybrid system is expected to be applied to various industrial processes in the future as it shows promises of the continuous culture system.
The corresponding authors, Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee noted that “The results of this research are technologies that can be applied to the production of various chemical substances as well as bioplastics, and are expected to be used as key parts needed in achieving carbon neutrality in the future.”
This research was received and performed with the supports from the CO2 Reduction Catalyst and Energy Device Technology Development Project, the Heterogeneous Atomic Catalyst Control Project, and the Next-generation Biorefinery Source Technology Development Project to lead the Biochemical Industry of the Oil-replacement Eco-friendly Chemical Technology Development Program by the Ministry of Science and ICT.
Figure 1. Schematic diagram and photo of the biohybrid CO2 electrolysis system.
(A) A conceptual scheme and (B) a photograph of the biohybrid CO2 electrolysis system. (C) A detailed scheme of reaction inside the system. Gaseous CO2 was converted to formate in the electrolyzer, and the formate was converted to PHB by the cells in the fermenter. The catholyte was developed so that it is compatible with both CO2 electrolysis and fermentation and was continuously circulated.
2023.03.30 View 6580 -
Using light to throw and catch atoms to open up a new chapter for quantum computing
The technology to move and arrange atoms, the most basic component of a quantum computer, is very important to Rydberg quantum computing research. However, to place the atoms at the desired location, the atoms must be captured and transported one by one using a highly focused laser beam, commonly referred to as an optical tweezer. and, the quantum information of the atoms is likely to change midway.
KAIST (President Kwang Hyung Lee) announced on the 27th that a research team led by Professor Jaewook Ahn of the Department of Physics developed a technology to throw and receive rubidium atoms one by one using a laser beam.
The research team developed a method to throw and receive atoms which would minimize the time the optical tweezers are in contact with the atoms in which the quantum information the atoms carry may change. The research team used the characteristic that the rubidium atoms, which are kept at a very low temperature of 40μK below absolute zero, move very sensitively to the electromagnetic force applied by light along the focal point of the light tweezers.
The research team accelerated the laser of an optical tweezer to give an optical kick to an atom to send it to a target, then caught the flying atom with another optical tweezer to stop it. The atom flew at a speed of 65 cm/s, and traveled up to 4.2 μm. Compared to the existing technique of guiding the atoms with the optical tweezers, the technique of throwing and receiving atoms eliminates the need to calculate the transporting path for the tweezers, and makes it easier to fix the defects in the atomic arrangement. As a result, it is effective in generating and maintaining a large number of atomic arrangements, and when the technology is used to throw and receive flying atom qubits, it will be used in studying new and more powerful quantum computing methods that presupposes the structural changes in quantum arrangements.
"This technology will be used to develop larger and more powerful Rydberg quantum computers," says Professor Jaewook Ahn. “In a Rydberg quantum computer,” he continues, “atoms are arranged to store quantum information and interact with neighboring atoms through electromagnetic forces to perform quantum computing. The method of throwing an atom away for quick reconstruction the quantum array can be an effective way to fix an error in a quantum computer that requires a removal or replacement of an atom.”
The research, which was conducted by doctoral students Hansub Hwang and Andrew Byun of the Department of Physics at KAIST and Sylvain de Léséleuc, a researcher at the National Institute of Natural Sciences in Japan, was published in the international journal, Optica, 0n March 9th. (Paper title: Optical tweezers throw and catch single atoms).
This research was carried out with the support of the Samsung Science & Technology Foundation.
<Figure 1> A schematic diagram of the atom catching and throwing technique. The optical tweezer on the left kicks the atom to throw it into a trajectory to have the tweezer on the right catch it to stop it.
2023.03.28 View 4171 -
KAIST researchers devises a technology to utilize ultrahigh-resolution micro-LED with 40% reduced self-generated heat
In the digitized modern life, various forms of future displays, such as wearable and rollable displays are required. More and more people are wanting to connect to the virtual world whenever and wherever with the use of their smartglasses or smartwatches. Even further, we’ve been hearing about medical diagnosis kit on a shirt and a theatre-hat. However, it is not quite here in our hands yet due to technical limitations of being unable to fit as many pixels as a limited surface area of a glasses while keeping the power consumption at the a level that a hand held battery can supply, all the while the resolution of 4K+ is needed in order to perfectly immerse the users into the augmented or virtual reality through a wireless smartglasses or whatever the device.
KAIST (President Kwang Hyung Lee) announced on the 22nd that Professor Sang Hyeon Kim's research team of the Department of Electrical and Electronic Engineering re-examined the phenomenon of efficiency degradation of micro-LEDs with pixels in a size of micrometers (μm, one millionth of a meter) and found that it was possible to fundamentally resolve the problem by the use of epitaxial structure engineering.
Epitaxy refers to the process of stacking gallium nitride crystals that are used as a light emitting body on top of an ultrapure silicon or sapphire substrate used for μLEDs as a medium.
μLED is being actively studied because it has the advantages of superior brightness, contrast ratio, and lifespan compared to OLED. In 2018, Samsung Electronics commercialized a product equipped with μLED called 'The Wall'. And there is a prospect that Apple may be launching a μLED-mounted product in 2025.
In order to manufacture μLEDs, pixels are formed by cutting the epitaxial structure grown on a wafer into a cylinder or cuboid shape through an etching process, and this etching process is accompanied by a plasma-based process. However, these plasmas generate defects on the side of the pixel during the pixel formation process.
Therefore, as the pixel size becomes smaller and the resolution increases, the ratio of the surface area to the volume of the pixel increases, and defects on the side of the device that occur during processing further reduce the device efficiency of the μLED. Accordingly, a considerable amount of research has been conducted on mitigating or removing sidewall defects, but this method has a limit to the degree of improvement as it must be done at the post-processing stage after the grown of the epitaxial structure is finished.
The research team identified that there is a difference in the current moving to the sidewall of the μLED depending on the epitaxial structure during μLED device operation, and based on the findings, the team built a structure that is not sensitive to sidewall defects to solve the problem of reduced efficiency due to miniaturization of μLED devices. In addition, the proposed structure reduced the self-generated heat while the device was running by about 40% compared to the existing structure, which is also of great significance in commercialization of ultrahigh-resolution μLED displays.
This study, which was led by Woo Jin Baek of Professor Sang Hyeon Kim's research team at the KAIST School of Electrical and Electronic Engineering as the first author with guidance by Professor Sang Hyeon Kim and Professor Dae-Myeong Geum of the Chungbuk National University (who was with the team as a postdoctoral researcher at the time) as corresponding authors, was published in the international journal, 'Nature Communications' on March 17th. (Title of the paper: Ultra-low-current driven InGaN blue micro light-emitting diodes for electrically efficient and self-heating relaxed microdisplay).
Professor Sang Hyeon Kim said, "This technological development has great meaning in identifying the cause of the drop in efficiency, which was an obstacle to miniaturization of μLED, and solving it with the design of the epitaxial structure.“ He added, ”We are looking forward to it being used in manufacturing of ultrahigh-resolution displays in the future."
This research was carried out with the support of the Samsung Future Technology Incubation Center.
Figure 1. Image of electroluminescence distribution of μLEDs fabricated from epitaxial structures with quantum barriers of different thicknesses while the current is running
Figure 2. Thermal distribution images of devices fabricated with different epitaxial structures under the same amount of light.
Figure 3. Normalized external quantum efficiency of the device fabricated with the optimized epitaxial structure by sizes.
2023.03.23 View 4372 -
KAIST research team develops clathrin assembly for targeted protein delivery to cancer cells
In order to effectively treat cancer without additional side effects, we need a way to deliver drugs specifically to tumor cells. Protein assemblies have been widely used for drug delivery in the field of cancer treatment, but to use them for drug delivery they must first be functionalized, meaning they must be bound to the protein that recognizes the target tumor cell and deliver a drug that kills it. However, the functionalization process of protein assemblies is very complex, inefficient, and limited to small-sized chemical drugs, which limits their real-life applicability.
On March 14, a KAIST research team led by Professor Hak-Sung Kim from the KAIST Department of Biological Sciences reported the development of a clathrin assembly that can specifically deliver drugs to cancer cells.
Clathrin assemblies transport materials efficiently through endocytosis in living organisms. They are formed by the self-assembly of triskelion units, which are composed of three heavy chains bonded with three light chains. Inspired by this mechanism, the research team designed a clathrin chain to facilitate the functionalization of tumor cell recognition proteins and toxin proteins in order to deliver drugs specifically to tumor cells. From this, the team created a new type of clathrin assembly.
Figure 1. (Upper) Schematic diagram of the development of a new clathrin assembly that simultaneously functionalizes two types of proteins (cancer cell recognition protein and toxin protein) on heavy and light chains of clathrin in a one-pot reaction (bottom, left) Electron microscopy image of clathrin assembly: formation of an assembly with a diameter of about 28 nanometers (bottom, right) Cancer cell killing effect of CLA: CLA functionalized with epidermal growth factor receptor (EGFR) recognition protein and toxin protein kills only the cancer cells that overexpress EGFR.
The newly developed clathrin assembly requires a one-pot reaction, meaning both the toxin and tumor-recognition proteins can be functionalized simultaneously and show high efficiency. As a result, this technique is expected to be used in a wide variety of applications in the fields of biology and medicine including drug delivery, vaccine development, and diagnosing illnesses.
In this research, an epidermal growth factor receptor (EGFR), a common tumor marker, was used as the recognition protein, allowing drug delivery only to tumor cells. The clathrin assemblies that were functionalized to recognize EGFR showed a bonding strength 900-times stronger than it normally would due to the avidity effect. Based on this finding, the research team confirmed that treatment with toxin-functionalized clathrin assembly led to effective cell death for tumor cells, while it showed no such effect on healthy cells.
This research by Dr. Hong-Sik Kim and his colleagues was published in Small volume 19, issue 8 on February 22 under the title, "Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery", and it was selected as the cover paper.
Figure 2. Cover Paper: This study was published in the international journal 'Small' on February 22nd, Volume 19, No. 8, and was selected as the cover paper.
First author Dr. Hong-Sik Kim said, “Clathrin is difficult to functionalize, and since it is extracted from mammals, realistic applications have been limited.” He added, “But the new clathrin assembly we designed for this research can be functionalized with two different types of proteins through a single-step reaction, and can be produced from E. coli, meaning it can become an applicable protein assembly technology for a wide range of biomedical fields.”
This research was funded by the Global Ph.D. Fellowship and the Mid-career Researcher Grant of the National Research Foundation.
2023.03.22 View 4035 -
KAIST leads AI-based analysis on drug-drug interactions involving Paxlovid
KAIST (President Kwang Hyung Lee) announced on the 16th that an advanced AI-based drug interaction prediction technology developed by the Distinguished Professor Sang Yup Lee's research team in the Department of Biochemical Engineering that analyzed the interaction between the PaxlovidTM ingredients that are used as COVID-19 treatment and other prescription drugs was published as a thesis. This paper was published in the online edition of 「Proceedings of the National Academy of Sciences of America」 (PNAS), an internationally renowned academic journal, on the 13th of March.
* Thesis Title: Computational prediction of interactions between Paxlovid and prescription drugs (Authored by Yeji Kim (KAIST, co-first author), Jae Yong Ryu (Duksung Women's University, co-first author), Hyun Uk Kim (KAIST, co-first author), and Sang Yup Lee (KAIST, corresponding author))
In this study, the research team developed DeepDDI2, an advanced version of DeepDDI, an AI-based drug interaction prediction model they developed in 2018. DeepDDI2 is able to compute for and process a total of 113 drug-drug interaction (DDI) types, more than the 86 DDI types covered by the existing DeepDDI.
The research team used DeepDDI2 to predict possible interactions between the ingredients (ritonavir, nirmatrelvir) of Paxlovid*, a COVID-19 treatment, and other prescription drugs. The research team said that while among COVID-19 patients, high-risk patients with chronic diseases such as high blood pressure and diabetes are likely to be taking other drugs, drug-drug interactions and adverse drug reactions for Paxlovid have not been sufficiently analyzed, yet. This study was pursued in light of seeing how continued usage of the drug may lead to serious and unwanted complications.
* Paxlovid: Paxlovid is a COVID-19 treatment developed by Pfizer, an American pharmaceutical company, and received emergency use approval (EUA) from the US Food and Drug Administration (FDA) in December 2021.
The research team used DeepDDI2 to predict how Paxrovid's components, ritonavir and nirmatrelvir, would interact with 2,248 prescription drugs. As a result of the prediction, ritonavir was predicted to interact with 1,403 prescription drugs and nirmatrelvir with 673 drugs.
Using the prediction results, the research team proposed alternative drugs with the same mechanism but low drug interaction potential for prescription drugs with high adverse drug events (ADEs). Accordingly, 124 alternative drugs that could reduce the possible adverse DDI with ritonavir and 239 alternative drugs for nirmatrelvir were identified.
Through this research achievement, it became possible to use an deep learning technology to accurately predict drug-drug interactions (DDIs), and this is expected to play an important role in the digital healthcare, precision medicine and pharmaceutical industries by providing useful information in the process of developing new drugs and making prescriptions.
Distinguished Professor Sang Yup Lee said, "The results of this study are meaningful at times like when we would have to resort to using drugs that are developed in a hurry in the face of an urgent situations like the COVID-19 pandemic, that it is now possible to identify and take necessary actions against adverse drug reactions caused by drug-drug interactions very quickly.”
This research was carried out with the support of the KAIST New-Deal Project for COVID-19 Science and Technology and the Bio·Medical Technology Development Project supported by the Ministry of Science and ICT.
Figure 1. Results of drug interaction prediction between Paxlovid ingredients and representative approved drugs using DeepDDI2
2023.03.16 View 5146 -
The cause of disability in aged brain meningeal membranes identified
Due to the increase in average age, studies on changes in the brain following general aging process without serious brain diseases have also become an issue that requires in-depth studies. Regarding aging research, as aging progresses, ‘sugar’ accumulates in the body, and the accumulated sugar becomes a causative agent for various diseases such as aging-related inflammation and vascular disease. In the end, “surplus” sugar molecules attach to various proteins in the body and interfere with their functions.
KAIST (President Kwang Hyung Lee), a joint research team of Professor Pilnam Kim and Professor Yong Jeong of the Department of Bio and Brain Engineering, revealed on the 15th that it was confirmed that the function of being the “front line of defense” for the cerebrocortex of the brain meninges, the layers of membranes that surrounds the brain, is hindered when 'sugar' begins to build up on them as aging progresses.
Professor Kim's research team confirmed excessive accumulation of sugar molecules in the meninges of the elderly and also confirmed that sugar accumulation occurs mouse models in accordance with certain age levels. The meninges are thin membranes that surround the brain and exist at the boundary between the cerebrospinal fluid and the cortex and play an important role in protecting the brain. In this study, it was revealed that the dysfunction of these brain membranes caused by aging is induced by 'excess' sugar in the brain. In particular, as the meningeal membrane becomes thinner and stickier due to aging, a new paradigm has been provided for the discovery of the principle of the decrease in material exchange between the cerebrospinal fluid and the cerebral cortex.
This research was conducted by the Ph.D. candidate Hyo Min Kim and Dr. Shinheun Kim as the co-first authors to be published online on February 28th in the international journal, Aging Cell. (Paper Title: Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging)
The meninges, which are in direct contact with the cerebrospinal fluid, are mainly composed of collagen, an extracellular matrix (ECM) protein, and are composed of fibroblasts, which are cells that produce this protein. The cells that come in contact with collagen proteins that are attached with sugar have a low collagen production function, while the meningeal membrane continuously thins and collapses as the expression of collagen degrading enzymes increases.
Studies on the relationship between excess sugar molecules accumulation in the brain due to continued sugar intake and the degeneration of neurons and brain diseases have been continuously conducted. However, this study was the first to identify meningeal degeneration and dysfunction caused by glucose accumulation with the focus on the meninges itself, and the results are expected to present new ideas for research into approach towards discoveries of new treatments for brain disease.
Researcher Hyomin Kim, the first author, introduced the research results as “an interesting study that identified changes in the barriers of the brain due to aging through a convergent approach, starting from the human brain and utilizing an animal model with a biomimetic meningeal model”.
Professor Pilnam Kim's research team is conducting research and development to remove sugar that accumulated throughout the human body, including the meninges. Advanced glycation end products, which are waste products formed when proteins and sugars meet in the human body, are partially removed by macrophages. However, glycated products bound to extracellular matrix proteins such as collagen are difficult to remove naturally. Through the KAIST-Ceragem Research Center, this research team is developing a healthcare medical device to remove 'sugar residue' in the body.
This study was carried out with the National Research Foundation of Korea's collective research support.
Figure 1. Schematic diagram of proposed mechanism showing aging‐related ECM remodeling through meningeal fibroblasts on the brain leptomeninges. Meningeal fibroblasts in the young brain showed dynamic COL1A1 synthetic and COL1‐interactive function on the collagen membrane. They showed ITGB1‐mediated adhesion on the COL1‐composed leptomeningeal membrane and induction of COL1A1 synthesis for maintaining the collagen membrane. With aging, meningeal fibroblasts showed depletion of COL1A1 synthetic function and altered cell–matrix interaction.
Figure 2. Representative rat meningeal images observed in the study. Compared to young rats, it was confirmed that type 1 collagen (COL1) decreased along with the accumulation of glycated end products (AGE) in the brain membrane of aged rats, and the activity of integrin beta 1 (ITGB1), a representative receptor corresponding to cell-collagen interaction. Instead, it was observed that the activity of discoidin domain receptor 2 (DDR2), one of the tyrosine kinases, increased.
Figure 3. Substance flux through the brain membrane decreases with aging. It was confirmed that the degree of adsorption of fluorescent substances contained in cerebrospinal fluid (CSF) to the brain membrane increased and the degree of entry into the periphery of the cerebral blood vessels decreased in the aged rats. In this study, only the influx into the brain was confirmed during the entry and exit of substances, but the degree of outflow will also be confirmed through future studies.
2023.03.15 View 4584 -
KAIST team develops smart immune system that can pin down on malignant tumors
A joint research team led by Professor Jung Kyoon Choi of the KAIST Department of Bio and Brain Engineering and Professor Jong-Eun Park of the KAIST Graduate School of Medical Science and Engineering (GSMSE) announced the development of the key technologies to treat cancers using smart immune cells designed based on AI and big data analysis. This technology is expected to be a next-generation immunotherapy that allows precision targeting of tumor cells by having the chimeric antigen receptors (CARs) operate through a logical circuit. Professor Hee Jung An of CHA Bundang Medical Center and Professor Hae-Ock Lee of the Catholic University of Korea also participated in this research to contribute joint effort.
Professor Jung Kyoon Choi’s team built a gene expression database from millions of cells, and used this to successfully develop and verify a deep-learning algorithm that could detect the differences in gene expression patterns between tumor cells and normal cells through a logical circuit. CAR immune cells that were fitted with the logic circuits discovered through this methodology could distinguish between tumorous and normal cells as a computer would, and therefore showed potentials to strike only on tumor cells accurately without causing unwanted side effects.
This research, conducted by co-first authors Dr. Joonha Kwon of the KAIST Department of Bio and Brain Engineering and Ph.D. candidate Junho Kang of KAIST GSMSE, was published by Nature Biotechnology on February 16, under the title Single-cell mapping of combinatorial target antigens for CAR switches using logic gates.
An area in cancer research where the most attempts and advances have been made in recent years is immunotherapy. This field of treatment, which utilizes the patient’s own immune system in order to overcome cancer, has several methods including immune checkpoint inhibitors, cancer vaccines and cellular treatments. Immune cells like CAR-T or CAR-NK equipped with chimera antigen receptors, in particular, can recognize cancer antigens and directly destroy cancer cells.
Starting with its success in blood cancer treatment, scientists have been trying to expand the application of CAR cell therapy to treat solid cancer. But there have been difficulties to develop CAR cells with effective killing abilities against solid cancer cells with minimized side effects. Accordingly, in recent years, the development of smarter CAR engineering technologies, i.e., computational logic gates such as AND, OR, and NOT, to effectively target cancer cells has been underway.
At this point in time, the research team built a large-scale database for cancer and normal cells to discover the exact genes that are expressed only from cancer cells at a single-cell level. The team followed this up by developing an AI algorithm that could search for a combination of genes that best distinguishes cancer cells from normal cells. This algorithm, in particular, has been used to find a logic circuit that can specifically target cancer cells through cell-level simulations of all gene combinations. CAR-T cells equipped with logic circuits discovered through this methodology are expected to distinguish cancerous cells from normal cells like computers, thereby minimizing side effects and maximizing the effects of chemotherapy.
Dr. Joonha Kwon, who is the first author of this paper, said, “this research suggests a new method that hasn’t been tried before. What’s particularly noteworthy is the process in which we found the optimal CAR cell circuit through simulations of millions of individual tumors and normal cells.” He added, “This is an innovative technology that can apply AI and computer logic circuits to immune cell engineering. It would contribute greatly to expanding CAR therapy, which is being successfully used for blood cancer, to solid cancers as well.”
This research was funded by the Original Technology Development Project and Research Program for Next Generation Applied Omic of the Korea Research Foundation.
Figure 1. A schematic diagram of manufacturing and administration process of CAR therapy and of cancer cell-specific dual targeting using CAR.
Figure 2. Deep learning (convolutional neural networks, CNNs) algorithm for selection of dual targets based on gene combination (left) and algorithm for calculating expressing cell fractions by gene combination according to logical circuit (right).
2023.03.09 View 6057 -
KAIST researchers develops a tech to enable production of ultrahigh-resolution LED with sub-micrometer scale pixels
Ultrahigh-resolution displays are an essential element for developing next-generation electronic products such as virtual reality (VR), augmented reality (AR), and smart watches, and can be applied not only to head-mounted displays, but also to smart glasses and smart lenses. The technology developed through this research is expected to be used to make such next-generation ultrahigh-resolution displays and other various sub-micro optoelectronic devices.
KAIST (President Kwang Hyung Lee) announced on the 22nd that Professor Yong-Hoon Cho's research team of KAIST Department of Physics developed the core technology for an ultrahigh resolution light-emitting diode (LED) display that can realize 0.5 micron-scale pixels smaller than 1/100 of the average hair thickness (about 100 microns) using focused ion beams.
Commonly, pixelation of ultrahigh-resolution LED displays usually relies on the etching method that physically cuts the area around the pixel, but as the pixel becomes smaller due to the occurrence of various defects around it, leading to side-effects of having leakage of current increased and light-emission efficiency decreased. In addition, various complex processes such as patterning for pixelation and post-processing for prevention of leakage current are required.
Professor Yong-Hoon Cho's research team developed a technology that can create pixels down to the size of a microscale without the complicated pre- and post-processing using a focused ion beam. This method has the advantage of being able to freely set the shape of the emitting pixel without causing any structural deformation on the material surface by controlling the intensity of the focused ion beam.
The focused ion beam technology has been widely used for ultrahigh-magnification imaging and nanostructure fabrication in fields such as materials engineering and biology. However, when a focused ion beam is used on a light emitting body such as an LED, light emission of a portion hit by the beam and a surrounding area rapidly decreases, which has been a barrier to fabricating a nano-scale light emitting structure. Upon facing this issue, Professor Cho's research team began the research on the idea that if they turned things around to use these problematic phenomena, they can be used in ultra-fine pixelation method on a sub-micron scale.
The research team used a focused ion beam whose intensity was softened to the extent that the surface was not shaved, and found that not only the light-emission rapidly decreased in the area hit by the focused ion beam, but also the local resistance greatly increased. As a result, while the surface of the LED is kept flat, the portion hit by the focused ion beam is optically and electrically isolated, enabling pixelation for independent operation.
Professor Yong-Hoon Cho, who led the research, said, “We have newly developed a technology that can create sub-micron-scale pixels without complicated processes using a focused ion beam, which will be a base technology that can be applied to next-generation ultrahigh-resolution displays and nano-photoelectronic devices.”
This research in which the Master's student Ji-Hwan Moon and the Ph.D. student Baul Kim of KAIST Department of Physics participated as co-first authors, was carried out with the support of the National Research Foundation of Korea's Support Program for Mid-Career Researchers and the Institute of Information and Communications Technology Planning and Evaluation. It was published online in 'Advanced Materials' on February 13, and was also selected as the internal cover of the next offline edition. (Title: Electrically Driven Sub-Micron Light-Emitting Diode Arrays Using Maskless and Etching-Free Pixelation)
Figure 1. Schematic diagram of the technology for ultrahigh density sub-micron-sized pixels through He focused ion beam (FIB) irradiation on an LED device
Figure 2. Ultra-high-density pixelation technology of micro light-emitting diodes (μLED) through He focused ion beam (FIB) irradiation
Figure 3. Rectangular pixels of different sizes (surface structure picture and luminescence picture) realized by a focused ion beam. Luminescence pictures of pixel arrays ranging in size from 20 µm x 20 µm to 0.5 µm x 0.5 µm, with surface flatness maintained.
2023.03.08 View 4736 -
KAIST Holds 2023 Commencement Ceremony
< Photo 1. On the 17th, KAIST held the 2023 Commencement Ceremony for a total of 2,870 students, including 691 doctors. >
KAIST held its 2023 commencement ceremony at the Sports Complex of its main campus in Daejeon at 2 p.m. on February 27. It was the first commencement ceremony to invite all its graduates since the start of COVID-19 quarantine measures.
KAIST awarded a total of 2,870 degrees including 691 PhD degrees, 1,464 master’s degrees, and 715 bachelor’s degrees, which adds to the total of 74,999 degrees KAIST has conferred since its foundation in 1971, which includes 15,772 PhD, 38,360 master’s and 20,867 bachelor’s degrees.
This year’s Cum Laude, Gabin Ryu, from the Department of Mechanical Engineering received the Minister of Science and ICT Award. Seung-ju Lee from the School of Computing received the Chairman of the KAIST Board of Trustees Award, while Jantakan Nedsaengtip, an international student from Thailand received the KAIST Presidential Award, and Jaeyong Hwang from the Department of Physics and Junmo Lee from the Department of Industrial and Systems Engineering each received the President of the Alumni Association Award and the Chairman of the KAIST Development Foundation Award, respectively.
Minister Jong-ho Lee of the Ministry of Science and ICT awarded the recipients of the academic awards and delivered a congratulatory speech.
Yujin Cha from the Department of Bio and Brain Engineering, who received a PhD degree after 19 years since his entrance to KAIST as an undergraduate student in 2004 gave a speech on behalf of the graduates to move and inspire the graduates and the guests.
After Cha received a bachelor’s degree from the Department of Nuclear and Quantum Engineering, he entered a medical graduate school and became a radiation oncology specialist. But after experiencing the death of a young patient who suffered from osteosarcoma, he returned to his alma mater to become a scientist. As he believes that science and technology is the ultimate solution to the limitations of modern medicine, he started as a PhD student at the Department of Bio and Brain Engineering in 2018, hoping to find such solutions.
During his course, he identified the characteristics of the decision-making process of doctors during diagnosis, and developed a brain-inspired AI algorithm. It is an original and challenging study that attempted to develop a fundamental machine learning theory from the data he collected from 200 doctors of different specialties.
Cha said, “Humans and AI can cooperate by humans utilizing the unique learning abilities of AI to develop our expertise, while AIs can mimic us humans’ learning abilities to improve.” He added, “My ultimate goal is to develop technology to a level at which humans and machines influence each other and ‘coevolve’, and applying it not only to medicine, but in all areas.”
Cha, who is currently an assistant professor at the KAIST Biomedical Research Center, has also written Artificial Intelligence for Doctors in 2017 to help medical personnel use AI in clinical fields, and the book was selected as one of the 2018 Sejong Books in the academic category.
During his speech at this year’s commencement ceremony, he shared that “there are so many things in the world that are difficult to solve and many things to solve them with, but I believe the things that can really broaden the horizons of the world and find fundamental solutions to the problems at hand are science and technology.”
Meanwhile, singer-songwriter Sae Byul Park who studied at the KAIST Graduate School of Culture Technology will also receive her PhD degree.
Natural language processing (NLP) is a field in AI that teaches a computer to understand and analyze human language that is actively being studied. An example of NLP is ChatGTP, which recently received a lot of attention. For her research, Park analyzed music rather than language using NLP technology.
To analyze music, which is in the form of sound, using the methods for NLP, it is necessary to rebuild notes and beats into a form of words or sentences as in a language. For this, Park designed an algorithm called Mel2Word and applied it to her research.
She also suggested that by converting melodies into texts for analysis, one would be able to quantitatively express music as sentences or words with meaning and context rather than as simple sounds representing a certain note.
Park said, “music has always been considered as a product of subjective emotion, but this research provides a framework that can calculate and analyze music.”
Park’s study can later be developed into a tool to measure the similarities between musical work, as well as a piece’s originality, artistry and popularity, and it can be used as a clue to explore the fundamental principles of how humans respond to music from a cognitive science perspective.
Park began her Ph.D. program in 2014, while carrying on with her musical activities as well as public and university lectures alongside, and dealing with personally major events including marriage and childbirth during the course of years. She already met the requirements to receive her degree in 2019, but delayed her graduation in order to improve the level of completion of her research, and finally graduated with her current achievements after nine years.
Professor Juhan Nam, who supervised Park’s research, said, “Park, who has a bachelor’s degree in psychology, later learned to code for graduate school, and has complete high-quality research in the field of artificial intelligence.” He added, “Though it took a long time, her attitude of not giving up until the end as a researcher is also excellent.”
Sae Byul Park is currently lecturing courses entitled Culture Technology and Music Information Retrieval at the Underwood International College of Yonsei University.
Park said, “the 10 or so years I’ve spent at KAIST as a graduate student was a time I could learn and prosper not only academically but from all angles of life.” She added, “having received a doctorate degree is not the end, but a ‘commencement’. Therefore, I will start to root deeper from the seeds I sowed and work harder as a both a scholar and an artist.”
< Photo 2. From left) Yujin Cha (Valedictorian, Medical-Scientist Program Ph.D. graduate), Saebyeol Park (a singer-songwriter, Ph.D. graduate from the Graduate School of Culture and Technology), Junseok Moon and Inah Seo (the two highlighted CEO graduates from the Department of Management Engineering's master’s program) >
Young entrepreneurs who dream of solving social problems will also be wearing their graduation caps. Two such graduates are Jun-seok Moon and Inah Seo, receiving their master’s degrees in social entrepreneurship MBA from the KAIST College of Business.
Before entrance, Moon ran a café helping African refugees stand on their own feet. Then, he entered KAIST to later expand his business and learn social entrepreneurship in order to sustainably help refugees in the blind spots of human rights and welfare.
During his master’s course, Moon realized that he could achieve active carbon reduction by changing the coffee alone, and switched his business field and founded Equal Table. The amount of carbon an individual can reduce by refraining from using a single paper cup is 10g, while changing the coffee itself can reduce it by 300g.
1kg of coffee emits 15kg of carbon over the course of its production, distribution, processing, and consumption, but Moon produces nearly carbon-neutral coffee beans by having innovated the entire process. In particular, the company-to-company ESG business solution is Moon’s new start-up area. It provides companies with carbon-reduced coffee made by roasting raw beans from carbon-neutral certified farms with 100% renewable energy, and shows how much carbon has been reduced in its making. Equal Table will launch the service this month in collaboration with SK Telecom, its first partner.
Inah Seo, who also graduated with Moon, founded Conscious Wear to start a fashion business reducing environmental pollution. In order to realize her mission, she felt the need to gain the appropriate expertise in management, and enrolled for the social entrepreneurship MBA.
Out of the various fashion industries, Seo focused on the leather market, which is worth 80 trillion won. Due to thickness or contamination issues, only about 60% of animal skin fabric is used, and the rest is discarded. Heavy metals are used during such processes, which also directly affects the environment.
During the social entrepreneurship MBA course, Seo collaborated with SK Chemicals, which had links through the program, and launched eco-friendly leather bags. The bags used discarded leather that was recycled by grinding and reprocessing into a biomaterial called PO3G. It was the first case in which PO3G that is over 90% biodegradable was applied to regenerated leather. In other words, it can reduce environmental pollution in the processing and disposal stages, while also reducing carbon emissions and water usage by one-tenth compared to existing cowhide products.
The social entrepreneurship MBA course, from which Moon and Seo graduated, will run in integration with the Graduate School of Green Growth as an Impact MBA program starting this year. KAIST plans to steadily foster entrepreneurs who will lead meaningful changes in the environment and society as well as economic values through innovative technologies and ideas.
< Photo 3. NYU President Emeritus John Sexton (left), who received this year's honorary doctorate of science, poses with President Kwang Hyung Lee >
Meanwhile, during this day’s commencement ceremony, KAIST also presented President Emeritus John Sexton of New York University with an honorary doctorate in science. He was recognized for laying the foundation for the cooperation between KAIST and New York University, such as promoting joint campuses.
< Photo 4. At the commencement ceremony of KAIST held on the 17th, President Kwang Hyung Lee is encouraging the graduates with his commencement address. >
President Kwang Hyung Lee emphasized in his commencement speech that, “if you can draw up the future and work hard toward your goal, the future can become a work of art that you create with your own hands,” and added, “Never stop on the journey toward your dreams, and do not give up even when you are met with failure. Failure happens to everyone, all the time. The important thing is to know 'why you failed', and to use those elements of failure as the driving force for the next try.”
2023.02.20 View 12890 -
Prof. Austin Givens of KAIST Language Center receives Ministerial Commendation
< Professor Austin Givens posing with the Letter of Commendation by the Miniser Hwang-Keun Chung of the Ministry of Agriculture, Food and Rural Affairs at the Language Center >
Professor Austin Givens of our Language Center received a Ministerial Commendation from the Korean Ministry of Agriculture, Food and Rural Affairs dated December 21st, 2022 for his contribution for the development of the Korean Foodservices Industry through his active and prominent media presence.
Professor Austin Givens has been working with the KAIST Language Center since 2017, and has shown his passion for Korean food through his YouTube channel "Austin! Eating What is Given", introducing not only the food but also the culture of Korea and KAIST to his international viewers through the videos he shares of his candid reviews of the food and restaurants around town on the popular video streaming platform.
< Thumbnail introductions of Professor Givens' videos on his YouTube channel, "Austin! Eating What is Given" >
- KAIST Language Center
2023.02.09 View 5866 -
KAIST presents a fundamental technology to remove metastatic traits from lung cancer cells
KAIST (President Kwang Hyung Lee) announced on January 30th that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering succeeded in using systems biology research to change the properties of carcinogenic cells in the lungs and eliminate both drug resistance and their ability to proliferate out to other areas of the body.
As the incidences of cancer increase within aging populations, cancer has become the most lethal disease threatening healthy life. Fatality rates are especially high when early detection does not happen in time and metastasis has occurred in various organs. In order to resolve this problem, a series of attempts were made to remove or lower the ability of cancer cells to spread, but they resulted in cancer cells in the intermediate state becoming more unstable and even more malignant, which created serious treatment challenges.
Professor Kwang-Hyun Cho's research team simulated various cancer cell states in the Epithelial-to-Mesenchymal Transition (EMT) of lung cancer cells, between epithelial cells without metastatic ability and mesenchymal cells with metastatic ability. A mathematical model of molecular network was established, and key regulators that could reverse the state of invasive and drug resistant mesenchymal cells back to the epithelial state were discovered through computer simulation analysis and molecular cell experiments. In particular, this process succeeded in properly reverting the mesenchymal lung cancer cells to a state where they were sensitive to chemotherapy treatment while avoiding the unstable EMT hybrid cell state in the middle process, which had remained a difficult problem.
The results of this research, in which KAIST Ph.D. student Namhee Kim, Dr. Chae Young Hwang, Researcher Taeyoung Kim, and Ph.D. student Hyunjin Kim participated, were published as an online paper in the international journal “Cancer Research” published by the American Association for Cancer Research (AACR) on January 30th. (Paper title: A cell fate reprogramming strategy reverses epithelial-to-mesenchymal transition of lung cancer cells while avoiding hybrid states)
Cells in an EMT hybrid state, which are caused by incomplete transitions during the EMT process in cancer cells, have the characteristics of both epithelial cells and mesenchymal cells, and are known to have high drug resistance and metastatic potential by acquiring high stem cell capacity. In particular, EMT is further enhanced through factors such as transforming growth factor-beta (TGF-β) secreted from the tumor microenvironment (TME) and, as a result, various cell states with high plasticity appear. Due to the complexity of EMT, it has been very difficult to completely reverse the transitional process of the mesenchymal cancer cells to an epithelial cell state in which metastatic ability and drug resistance are eliminated while avoiding the EMT hybrid cell state with high metastatic ability and drug resistance.
Professor Kwang-Hyun Cho's research team established a mathematical model of the gene regulation network that governs the complex process of EMT, and then applied large-scale computer simulation analysis and complex system network control technology to identify and verify 'p53', 'SMAD4', and 'ERK1' and 'ERK 2' (collectively ERKs) through molecular cell experiments as the three key molecular targets that can transform lung cancer cells in the mesenchymal cell state, reversed back to an epithelial cell state that no longer demonstrates the ability to metastasize, while avoiding the EMT hybrid cell state.
In particular, by analyzing the molecular regulatory mechanism of the complex EMT process at the system level, the key pathways were identified that were linked to the positive feedback that plays an important role in completely returning cancer cells to an epithelial cell state in which metastatic ability and drug resistance are removed.
This discovery is significant in that it proved that mesenchymal cells can be reverted to the state of epithelial cells under conditions where TGF-β stimulation are present, like they are in the actual environment where cancer tissue forms in the human body.
Abnormal EMT in cancer cells leads to various malignant traits such as the migration and invasion of cancer cells, changes in responsiveness to chemotherapy treatment, enhanced stem cell function, and the dissemination of cancer. In particular, the acquisition of the metastatic ability of cancer cells is a key determinant factor for the prognosis of cancer patients. The EMT reversal technology in lung cancer cells developed in this research is a new anti-cancer treatment strategy that reprograms cancer cells to eliminate their high plasticity and metastatic potential and increase their responsiveness to chemotherapy.
Professor Kwang-Hyun Cho said, "By succeeding in reversing the state of lung cancer cells that acquired high metastatic traits and resistance to drugs and reverting them to a treatable epithelial cell state with renewed sensitivity to chemotherapy, the research findings propose a new strategy for treatments that can improve the prognosis of cancer patients.”
Professor Kwang-Hyun Cho's research team was the first to present the principle of reversal treatment to revert cancer cells to normal cells, following through with the announcement of the results of their study that reverted colon cancer cells to normal colon cells in January of 2020, and also presenting successful re-programming research where the most malignant basal type breast cancer cells turned into less-malignant luminal type breast cancer cells that were treatable with hormonal therapies in January of 2022. This latest research result is the third in the development of reversal technology where lung cancer cells that had acquired metastatic traits returned to a state in which their metastatic ability was removed and drug sensitivity was enhanced.
This research was carried out with support from the Ministry of Science and ICT and the National Research Foundation of Korea's Basic Research in Science & Engineering Program for Mid-Career Researchers.
< Figure 1. Construction of the mathematical model of the regulatory network to represent the EMT phenotype based on the interaction between various molecules related to EMT.
(A) Professor Kwang-Hyun Cho's research team investigated numerous literatures and databases related to complex EMT, and based on comparative analysis of cell line data showing epithelial and mesenchymal cell conditions, they extracted key signaling pathways related to EMT and built a mathematical model of regulatory network (B) By comparing the results of computer simulation analysis and the molecular cell experiments, it was verified how well the constructed mathematical model simulated the actual cellular phenomena. >
< Figure 2. Understanding of various EMT phenotypes through large-scale computer simulation analysis and complex system network control technology.
(A) Through computer simulation analysis and experiments, Professor Kwang-Hyun Cho's research team found that complete control of EMT is impossible with single-molecule control alone. In particular, through comparison of the relative stability of attractors, it was revealed that the cell state exhibiting EMT hybrid characteristics has unstable properties. (B), (C) Based on these results, Prof. Cho’s team identified two feedbacks (positive feedback consisting of Snail-miR-34 and ZEB1-miR-200) that play an important role in avoiding the EMT hybrid state that appeared in the TGF-β-ON state. It was found through computer simulation analysis that the two feedbacks restore relatively high stability when the excavated p53 and SMAD4 are regulated. In addition, molecular cell experiments demonstrated that the expression levels of E-cad and ZEB1, which are representative phenotypic markers of EMT, changed similarly to the expression profile in the epithelial cell state, despite the TGF-β-ON state. >
< Figure 3. Complex molecular network analysis and discovery of reprogramming molecular targets for intact elimination of EMT hybrid features.
(A) Controlling the expression of p53 and SMAD4 in lung cancer cell lines was expected to overcome drug resistance, but contrary to expectations, chemotherapy responsiveness was not restored. (B) Professor Kwang-Hyun Cho's research team additionally analyzed computer simulations, genome data, and experimental results and found that high expression levels of TWIST1 and EPCAM were related to drug resistance. (C) Prof. Cho’s team identified three key molecular targets: p53, SMAD4 and ERK1 & ERK2. (D), (E) Furthermore, they identified a key pathway that plays an important role in completely reversing into epithelial cells while avoiding EMT hybrid characteristics, and confirmed through network analysis and attractor analysis that high stability of the key pathway was restored when the proposed molecular target was controlled. >
< Figure 4. Verification through experiments with lung cancer cell lines.
When p53 was activated and SMAD4 and ERK1/2 were inhibited in lung cancer cell lines, (A), (B) E-cad protein expression increased and ZEB1 protein expression decreased, and (C) mesenchymal cell status including TWIST1 and EPCAM and gene expression of markers related to stem cell potential characteristics were completely inhibited. In addition, (D) it was confirmed that resistance to chemotherapy treatment was also overcome as the cell state was reversed by the regulated target. >
< Figure 5. A schematic representation of the research results.
Prof. Cho’s research team identified key molecular regulatory pathways to avoid high plasticity formed by abnormal EMT of cancer cells and reverse it to an epithelial cell state through systems biology research. From this analysis, a reprogramming molecular target that can reverse the state of mesenchymal cells with acquired invasiveness and drug resistance to the state of epithelial cells with restored drug responsiveness was discovered.
For lung cancer cells, when a drug that enhances the expression of p53, one of the molecular targets discovered, and inhibits the expression of SMAD4 and ERK1 & ERK2 is administered, the molecular network of genes in the state of mesenchymal cells is modified, eventually eliminating metastatic ability and it is reprogrammed to turn into epithelial cells without the resistance to chemotherapy treatments. >
2023.01.30 View 11756