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A 20-year-old puzzle solved: KAIST research team reveals the 'three-dimensional vortex' of zero-dimensional ferroelectrics
Materials that can maintain a magnetized state by themselves without an external magnetic field (i.e., permanent magnets) are called ferromagnets. Ferroelectrics can be thought of as the electric counterpart to ferromagnets, as they maintain a polarized state without an external electric field. It is well-known that ferromagnets lose their magnetic properties when reduced to nano sizes below a certain threshold. What happens when ferroelectrics are similarly made extremely small in all directions (i.e., into a zero-dimensional structure such as nanoparticles) has been a topic of controversy for a long time.
< (From left) Professor Yongsoo Yang, the corresponding author, and Chaehwa Jeong, the first author studying in the integrated master’s and doctoral program, of the KAIST Department of Physics >
The research team led by Dr. Yongsoo Yang from the Department of Physics at KAIST has, for the first time, experimentally clarified the three-dimensional, vortex-shaped polarization distribution inside ferroelectric nanoparticles through international collaborative research with POSTECH, SNU, KBSI, LBNL and University of Arkansas.
About 20 years ago, Prof. Laurent Bellaiche (currently at University of Arkansas) and his colleagues theoretically predicted that a unique form of polarization distribution, arranged in a toroidal vortex shape, could occur inside ferroelectric nanodots. They also suggested that if this vortex distribution could be properly controlled, it could be applied to ultra-high-density memory devices with capacities over 10,000 times greater than existing ones. However, experimental clarification had not been achieved due to the difficulty of measuring the three-dimensional polarization distribution within ferroelectric nanostructures.
The research team at KAIST successfully solved this 20-year-old challenge by implementing a technique called atomic electron tomography. This technique works by acquiring atomic-resolution transmission electron microscope images of the nanomaterials from multiple tilt angles, and then reconstructing them back into three-dimensional structures using advanced reconstruction algorithms. Electron tomography can be understood as essentially the same method with the CT scans used in hospitals to view internal organs in three dimensions; the KAIST team adapted it uniquely for nanomaterials, utilizing an electron microscope at the single-atom level.
< Figure 1. Three-dimensional polarization distribution of BaTiO3 nanoparticles revealed by atomic electron tomography. >(Left) Schematic of the electron tomography technique, which involves acquiring transmission electron microscope images at multiple tilt angles and reconstructing them into 3D atomic structures.(Center) Experimentally determined three-dimensional polarization distribution inside a BaTiO3 nanoparticle via atomic electron tomography. A vortex-like structure is clearly visible near the bottom (blue dot).(Right) A two-dimensional cross-section of the polarization distribution, thinly sliced at the center of the vortex, with the color and arrows together indicating the direction of the polarization. A distinct vortex structure can be observed.
Using atomic electron tomography, the team completely measured the positions of cation atoms inside barium titanate (BaTiO3) nanoparticles, a well-known ferroelectric material, in three dimensions. From the precisely determined 3D atomic arrangements, they were able to further calculate the internal three-dimensional polarization distribution at the single-atom level. The analysis of the polarization distribution revealed, for the first time experimentally, that topological polarization orderings including vortices, anti-vortices, skyrmions, and a Bloch point occur inside the 0-dimensional ferroelectrics, as theoretically predicted 20 years ago. Furthermore, it was also found that the number of internal vortices can be controlled depending on their sizes.
Prof. Sergey Prosandeev and Prof. Bellaiche (who proposed with other co-workers the polar vortex ordering theoretically 20 years ago), joined this collaboration and further proved that the vortex distribution results obtained from experiments are consistent with theoretical calculations.
By controlling the number and orientation of these polarization distributions, it is expected that this can be utilized into next-generation high-density memory device that can store more than 10,000 times the amount of information in the same-sized device compared to existing ones.
Dr. Yang, who led the research, explained the significance of the results: “This result suggests that controlling the size and shape of ferroelectrics alone, without needing to tune the substrate or surrounding environmental effects such as epitaxial strain, can manipulate ferroelectric vortices or other topological orderings at the nano-scale. Further research could then be applied to the development of next-generation ultra-high-density memory.”
This research, with Chaehwa Jeong from the Department of Physics at KAIST as the first author, was published online in Nature Communications on May 8th (Title: Revealing the Three-Dimensional Arrangement of Polar Topology in Nanoparticles).
The study was mainly supported by the National Research Foundation of Korea (NRF) Grants funded by the Korean Government (MSIT).
2024.05.31 View 3573 -
Novel High-performance and Sustainable Paper Coating Material created by KAIST-Yonsei University Research Team to reduce microplastic pollution
What if there is a biodegradable packaging material with high performance without leaving microplastics?
Plastic pollution presents a global challenge that must be solved. In particular, packaging accounts for 30-50% of the total plastic consumption. While paper packaging is eco-friendly, it lacks crucial functionalities like moisture resistance and strength. Traditional coating materials exacerbate plastic pollution, prompting the need for sustainable alternatives.
Polyethylene (PE) and ethylene vinyl alcohol (EVOH) are typically used as coating materials to improve the low barrier properties of paper packaging, but these substances do not decompose and worsen microplastic pollution when disposed of in the natural environment. In response to this problem, packaging materials made from bio-based substances and biodegradable plastics have been developed, but in most cases, as the packaging performance improves, the biodegradability diminishes rapidly.
KAIST announced that a joint research team led by Professor Jaewook Myung of the Department of Civil and Environmental Engineering, Professor Hanseul Yang of the Department of Life Sciences, and Professor Jongcheol Seo of the Department of Packaging and Logistics <Figure 4. Back cover art of Green Chemistry journal of the latest volume, describing the boric acid cross-linked poly(vinyl alcohol) coated paper featuring marine biodegradability, biocompatibility, high barrier properties, and robustness developed through this study.>
at Yonsei University tackled the challenge of balancing packaging performance and sustainability. They successfully developed a sustainable, marine biodegradable, high-performance paper coating material.
* Biodegradable plastic: A plastic that can be decomposed by microorganisms in natural environments such as soil and ocean or artificial conditions such as industrial composting and anaerobic digestion by microorganisms.
*Microplastics: Tiny pieces of plastic less than 5 mm, produced during the decomposition of bulk plastic materials. Microplastics can persist in the sea for more than decades, causing severe marine pollution.
The team utilized boric acid-crosslinked poly(vinyl alcohol) (PVA), a biodegradable plastic, to coat the paper, thereby enhancing its biodegradability, barrier properties, and strength. The resulting coated paper exhibited superior performance compared to conventional plastics, with excellent barrier properties and physical strength, even in humid conditions.
<Figure 1. (a) Chemical structure of boric acid-crosslinked poly(vinyl alcohol) coating on paper, (b-c) Oxygen and water vapor barrier properties, (d-f) Tensile strength in dry and moist conditions. OTR: Oxygen transmission rate, WVTR: Water vapor transmission rate.>
The team also conducted an in-depth examination of biodegradation and biocompatibility to systematically evaluate the sustainability of the newly developed coated paper. Biodegradation was assessed by simulating the marine environment, known for its challenging biodegradability conditions. The team employed a respiratory system-based bioreactor to measure the degree of carbon mineralization into carbon dioxide. After 111 days of biodegradation, it was found that the coated papers achieved 59-82% biodegradation depending on the coating component. The phenomenon in which marine bacteria are decomposing the coating material was captured through a scanning electron microscope. In addition, in vitro biocompatibility was confirmed through human embryonic kidney and mouse embryonic fibroblast cells, as well as high in-vivo biocompatibility of the coated paper was verified through mouse experiments.
Through this study, the joint research team proposed a coating strategy that can improve packaging performance while upholding sustainability to address the drawbacks of paper packaging. The boric acid-crosslinked PVA-coated paper eliminates the need for artificial composting conditions or sewage treatment facilities. Being biodegradable in natural environments and characterized by low toxicity, this newly coated paper does not exacerbate environmental pollution when accidentally discarded. Thus, it presents a sustainable substitute for plastic packaging materials.
<Figure 2. (a) Normal paper and boric acid-crosslinked poly(vinyl alcohol) coated paper, (b) Biodegradation of the coated paper by marine bacteria, (c) Result of cytotoxicity test using human embryonic kidney and mouse embryonic fibroblast cells. (d) Vital organs after one-month exposure of the coated papers to mice.>
Professor Jaewook Myung at KAIST, who led the sustainability study of coated paper, said, "The development of a marine biodegradable high-performance paper coating is the result of combining the innovative technologies of three leading research teams in each field." He said, “We will continue to develop sustainable materials with excellent performance.” Meanwhile, Professor Jongchul Seo of Yonsei University, who led the research on the development of high-performance paper coating, mentioned, “Through this research, we have developed a sustainable paper packaging technology that can replace non-degradable plastic packaging, and we expect the research outcome will be applied in industry,”.
<Figure 3. End-of-life scenario of papers coated by BA-crosslinked PVA in the marine environment. The coated papers potentially be disintegrated by marine microorganisms and ocean waves and tides. The depolymerization of PVA coating and paper is then mediated by extracellular depolymerases such as oxidases and cellulases, after which the small subunits (oligomers and monomers) are assimilated by microbial cells. The carbon components in the coated papers are ultimately mineralized into CO2, posing no harm in the ocean.>
The work was published in Green Chemistry and Food Chemistry journals. This study was conducted with the support of the Korea Research Foundation and the Korea Institute for Agriculture, Food and Rural Affairs Technology Planning and Evaluation, etc.
*Title of paper published in Green Chemistry: Boric acid-crosslinked poly(vinyl alcohol): biodegradable, biocompatible, robust, and high-barrier paper coating
※ Selected as the article for the back cover of the journal .
- Authors: Shinhyeong Choe, Seulki You, Kitae Park, Youngju Kim, Jehee Park, Yongjun Cho, Jongchul Seo, Hanseul Yang, and Jaewook Myung)
- Date: April 17, 2024
- DOI: 10.1039/D4GC00618F
*Title of paper published in Food Chemistry: Effect of epichlorohydrin treatment on the coating process and performance of high-barrier paper packaging
- Authors: Kitae Park, Shinhyeong Choe, Kambiz Sadeghi, Pradeep Kumar Panda, Jaewook Myung, Dowan Kim, and Jongchul Seo
- Date: February 19, 2024
- DOI: 10.1016/j.foodchem.2024.138772
<Figure 4. Back cover art of Green Chemistry journal of the latest volume, describing the boric acid cross-linked poly(vinyl alcohol) coated paper featuring marine biodegradability, biocompatibility, high barrier properties, and robustness developed through this study.>
2024.05.22 View 3860 -
KAIST begins full-scale cooperation with Taiwan’s Formosa Group
< (From left) Senior Vice President for Planning and Budget Kyung-Soo Kim, and Professor Minee Choi of the Department of Brain and Cognitive Sciences of KAIST along with Chairman of Formosa Group Sandy Wang and KAIST President Kwang-Hyung Lee, and Dean Daesoo Kim of KAIST College of Life Science and Bioengineering >
KAIST is pursuing cooperation in the fields of advanced biotechnology and eco-friendly energy with Formosa Plastics Group, one of Taiwan's three largest companies.
To this end, Chairman Sandy Wang, a member of Formosa Group's standing committee and leader of the group's bio and eco-friendly energy sector, will visit KAIST on the 13th of this month. This is the first time that the owner of Formosa Group has made an official visit to KAIST.
Cooperation between the two institutions began last March when our university signed a memorandum of understanding on comprehensive exchange and cooperation with Ming Chi University of Science and Technology (明志科技大學), Chang Gung University(長庚大學), and Chang Gung Memorial Hospital(長庚記念醫院), three of many institutions established and supported by Formosa Group.
Based on this, Chairman Sandy Wang, who visits our university to promote more exchanges and cooperation, talked about ‘the education of children and corporate social return and practice of his father, Chairman Yung-Ching Wang,’ through a special lecture for the school leadership as a part of the Monthly Lecture on KAIST’s Leadership Innovation Day.
She then visited KAIST's research and engineering facilities related to Taiwan's future industries, such as advanced biotechnology and eco-friendly energy, and discussed global industry-academic cooperation plans. In the future, the two organizations plan to appoint adjunct professors and promote practical global cooperation, including joint student guidance and research cooperation. We plan to pursue effective mid- to long-term cooperation, such as conducting battery application research with the KAIST Next-Generation ESS Research Center and opening a graduate program specialized in stem cell and gene editing technology in connection with Chang Gung University and Chang Gung Memorial Hospital. The newly established cooperative relationship will also promote Formosa Group's investment and cooperation with KAIST's outstanding venture companies related to bio and eco-friendly energy to lay the foundation for innovative industrial cooperation between Taiwan and Korea.
President Kwang-Hyung Lee said, “The Formosa Group has a global network, so we regard it to be a key partner that will position KAIST’s bio and engineering technology in the global stages.” He also said, “With Chairman Sandy Wang’s visit, Taiwan is emerging as a global economic powerhouse,” and added, “We expect to continue our close cooperative relationship with the company.”
Formosa Group is a company founded by the late Chairman Yung-Ching Wang, the father of Chairman Sandy Wang. As the world's No. 1 plastic PVC producer, it is leading the core industries of Taiwan's economy, including semiconductors, steel, heavy industry, bio, and batteries. Chairman Yung-Ching Wang was respected by the Taiwanese people by setting an example of returning his wealth to society under the belief that the companies and assets he built ‘belonged to the people.’ Chang Gung University, Chang Gung Memorial Hospital, and Ming Chi University of Technology, which are pursuing cooperation with our university, were also established as part of the social contribution promoted by Chairman Yung-Ching Wang and are receiving financial support from Formosa Group.
2024.05.09 View 1488 -
Revolutionary 'scLENS' Unveiled to Decode Complex Single-Cell Genomic Data
Unlocking biological information from complex single-cell genomic data has just become easier and more precise, thanks to the innovative 'scLENS' tool developed by the Biomedical Mathematics Group within the IBS Center for Mathematical and Computational Sciences led by Chief Investigator Jae Kyoung Kim, who is also a professor at KAIST. This new finding represents a significant leap forward in the field of single-cell transcriptomics.
Single-cell genomic analysis is an advanced technique that measures gene expression at the individual cell level, revealing cellular changes and interactions that are not observable with traditional genomic analysis methods. When applied to cancer tissues, this analysis can delineate the composition of diverse cell types within a tumor, providing insights into how cancer progresses and identifying key genes involved during each stage of progression.
Despite the immense potential of single-cell genomic analysis, handling the vast amount of data that it generates has always been challenging. The amount of data covers the expression of tens of thousands of genes across hundreds to thousands of individual cells. This not only results in large datasets but also introduces noise-related distortions, which arise in part due to current measurement limitations.
< Figure 1. Overview of scLENS (single-cell Low-dimensional embedding using the effective Noise Subtract) >
(Left) Current dimensionality reduction methods for scRNA-seq data involve conventional data preprocessing steps, such as log normalization, followed by manual selection of signals from the scaled data. However, this study reveals that the high levels of sparsity and variability in scRNA-seq data can lead to signal distortion during the data preprocessing, compromising the accuracy of downstream analyses.
(Right) To address this issue, the researchers integrated L2 normalization into the conventional preprocessing pipeline, effectively mitigating signal distortion. Moreover, they developed a novel signal detection algorithm that eliminates the need for user intervention by leveraging random matrix theory-based noise filtering and signal robustness testing. By incorporating these techniques, scLENS enables accurate and automated analysis of scRNA-seq data, overcoming the limitations of existing dimensionality reduction methods.
Corresponding author Jae Kyoung Kim highlighted, “There has been a remarkable advancement in experimental technologies for analyzing single-cell transcriptomes over the past decade. However, due to limitations in data analysis methods, there has been a struggle to fully utilize valuable data obtained through extensive cost and time."
Researchers have developed numerous analysis methods over the years to discern biological signals from this noise. However, the accuracy of these methods has been less than satisfactory. A critical issue is that determining signal and noise thresholds often depends on subjective decisions from the users.
The newly developed scLENS tool harnesses Random Matrix Theory and Signal robustness test to automatically differentiate signals from noise without relying on subjective user input.
First author Hyun Kim stated, "Previously, users had to arbitrarily decide the threshold for signal and noise, which compromised the reproducibility of analysis results and introduced subjectivity. scLENS eliminates this problem by automatically detecting signals using only the inherent structure of the data."
During the development of scLENS, researchers identified the fundamental reasons for inaccuracies in existing analysis methods. They found that commonly used data preprocessing methods distort both biological signals and noise. The new preprocessing approach that scLENS offers is free from such distortions.
By resolving issues related to noise threshold determined by subjective user choice and signal distortion in conventional data preprocessing, scLENS significantly outperforms existing methods in accuracy. Additionally, scLENS automates the laborious process of signal dimension selection, allowing researchers to extract biological signals conveniently and automatically.
CI Kim added, "scLENS solves major issues in single-cell transcriptome data analysis, substantially improving the accuracy and efficiency throughout the analysis process. This is a prime example of how fundamental mathematical theories can drive innovation in life sciences research, allowing researchers to more quickly and accurately answer biological questions and uncover secrets of life that were previously hidden."
This research was published in the international journal 'Nature Communications' on April 27.
Terminology
* Single-cell RNA sequencing (scRNA-seq): A technique used to measure gene expression levels in individual cells, providing insights into cell heterogeneity and rare cell types.
* Dimensionality reduction: A method to reduce the number of features or variables in a dataset while preserving the most important information, making data analysis more manageable and interpretable.
* Random matrix theory: A mathematical framework used to model and analyze the properties of large, random matrices, which can be applied to filter out noise in high-dimensional data.
* Signal robustness test: Among the signals, this test selects signals that are robust to the slight perturbation in data because real biological signals should be invariant for such slight modification in the data.
2024.05.09 View 2634 -
KAIST researchers developed a novel ultra-low power memory for neuromorphic computing
A team of Korean researchers is making headlines by developing a new memory device that can be used to replace existing memory or used in implementing neuromorphic computing for next-generation artificial intelligence hardware for its low processing costs and its ultra-low power consumption.
KAIST (President Kwang-Hyung Lee) announced on April 4th that Professor Shinhyun Choi's research team in the School of Electrical Engineering has developed a next-generation phase change memory* device featuring ultra-low-power consumption that can replace DRAM and NAND flash memory.
☞ Phase change memory: A memory device that stores and/or processes information by changing the crystalline states of materials to be amorphous or crystalline using heat, thereby changing its resistance state.
Existing phase change memory has the problems such as expensive fabrication process for making highly scaled device and requiring substantial amount of power for operation. To solve these problems, Professor Choi’s research team developed an ultra-low power phase change memory device by electrically forming a very small nanometer (nm) scale phase changeable filament without expensive fabrication processes. This new development has the groundbreaking advantage of not only having a very low processing cost but also of enabling operating with ultra-low power consumption.
DRAM, one of the most popularly used memory, is very fast, but has volatile characteristics in which data disappears when the power is turned off. NAND flash memory, a storage device, has relatively slow read/write speeds, but it has non-volatile characteristic that enables it to preserve the data even when the power is cut off.
Phase change memory, on the other hand, combines the advantages of both DRAM and NAND flash memory, offering high speed and non-volatile characteristics. For this reason, phase change memory is being highlighted as the next-generation memory that can replace existing memory, and is being actively researched as a memory technology or neuromorphic computing technology that mimics the human brain.
However, conventional phase change memory devices require a substantial amount of power to operate, making it difficult to make practical large-capacity memory products or realize a neuromorphic computing system. In order to maximize the thermal efficiency for memory device operation, previous research efforts focused on reducing the power consumption by shrinking the physical size of the device through the use of the state-of-the-art lithography technologies, but they were met with limitations in terms of practicality as the degree of improvement in power consumption was minimal whereas the cost and the difficulty of fabrication increased with each improvement.
In order to solve the power consumption problem of phase change memory, Professor Shinhyun Choi’s research team created a method to electrically form phase change materials in extremely small area, successfully implementing an ultra-low-power phase change memory device that consumes 15 times less power than a conventional phase change memory device fabricated with the expensive lithography tool.
< Figure 1. Illustrations of the ultra-low power phase change memory device developed through this study and the comparison of power consumption by the newly developed phase change memory device compared to conventional phase change memory devices. >
Professor Shinhyun Choi expressed strong confidence in how this research will span out in the future in the new field of research saying, "The phase change memory device we have developed is significant as it offers a novel approach to solve the lingering problems in producing a memory device at a greatly improved manufacturing cost and energy efficiency. We expect the results of our study to become the foundation of future electronic engineering, enabling various applications including high-density three-dimensional vertical memory and neuromorphic computing systems as it opened up the possibilities to choose from a variety of materials.” He went on to add, “I would like to thank the National Research Foundation of Korea and the National NanoFab Center for supporting this research.”
This study, in which See-On Park, a student of MS-PhD Integrated Program, and Seokman Hong, a doctoral student of the School of Electrical Engineering at KAIST, participated as first authors, was published on April 4 in the April issue of the renowned international academic journal Nature. (Paper title: Phase-Change Memory via a Phase-Changeable Self-Confined Nano-Filament)
This research was conducted with support from the Next-Generation Intelligent Semiconductor Technology Development Project, PIM AI Semiconductor Core Technology Development (Device) Project, Excellent Emerging Research Program of the National Research Foundation of Korea, and the Semiconductor Process-based Nanomedical Devices Development Project of the National NanoFab Center.
2024.04.04 View 4395 -
KAIST Research Team Creates the Scent of Jasmine from Microorganisms
The fragrance of jasmine and ylang-ylang, used widely in the manufacturing of cosmetics, foods, and beverages, can be produced by direct extraction from their respective flowers. In reality, this makes it difficult for production to meet demand, so companies use benzyl acetate, a major aromatic component of the two fragrances that is chemically synthesized from raw materials derived from petroleum.
On February 26, a KAIST research team led by Research Professor Kyeong Rok Choi from the BioProcess Engineering Research Center and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering revealed the development of the first microbial process to effectively produce benzyl acetate, an industrially useful compound, from renewable carbon sources such as glucose. The results were published in their paper titled “A microbial process for the production of benzyl acetate”.
< Figure 1. Production of benzyl acetate through co-culture of upstream and downstream strains harboring the benzoic acid-dependent pathway. >
The team, led by Distinguished Professor Lee, aimed to produce benzyl acetate through an environmentally friendly and sustainable method, and developed an Escherichia coli strand to convert glucose into benzyl acetate through system metabolic engineering*.
*System metabolic engineering: a field of research founded by Distinguished Professor Lee to effectively develop microbial cell plants, a core component of the bio-industry that will replace the existing chemical industry, which is highly dependent on petroleum.
The research team developed a metabolic pathway that biosynthesizes benzyl acetate from benzoic acid derived from glucose, and successfully produced benzyl acetate by co-culturing** the strain.
**co-culture: simultaneously synthesizing two or more types of microorganisms in a mixture
However, it has been confirmed that the enzyme used to convert benzoic acid into benzyl acetate in this co-culturing technique acts non-specifically on an intermediate product during benzoic acid biosynthesis, producing a by-product called cinnamyl acetate. This process consumes the intermediate product needed for benzoic acid biosynthesis, thereby reducing the production efficiency of the target compound, benzyl acetate.
To overcome this problem, Distinguished Professor Lee and his team devised a delayed co-culture method, where they first produced benzoic acid in the earlier stages of fermentation by only culturing the top strain that produces benzoic acid from glucose, and later inoculated the bottom strain to convert the accumulated benzoic acid in the culture medium into benzyl acetate.
By applying this co-culture technique, the team suppressed the formation of by-products without further strain improvement or applying additional enzymes, and multiplied the concentration of the target compound by 10 times, producing 2.2 g/L of benzyl acetate. In addition, the team confirmed its potential for the commercial production of benzyl acetate through a technical economic analysis on this microbial process.
< Figure 2. Delayed co-culture of the Bn1 and Bn-BnAc3 strains for improved production of benzyl acetate through the benzoic acid-independent pathway.>
Research Professor Keyong Rok Choi, who was the first author of this paper, said, “This work is significant in that we have developed an effective microbial process to produce the industrially useful compound benzyl acetate, and also in that we have suggested a new approach to overcome the target chemical efficiency diminution and by-product formation issues caused commonly through non-specific enzyme activities during metabolic engineering.”
Distinguished Professor Lee said, “If we can increase the variety and number of microbial processes that produce useful chemicals through sustainable methods and at the same time develop effective strategies to solve chronic and inevitable problems that arise during microbial strain development, we will be able to accelerate the transition from the petrochemical industry into the eco-friendly and sustainable bio-industry.
This work was published online in Nature Chemical Engineering, issued by Nature.
This research was supported by the ‘Implementation of Intelligent Cell Factory Technology (PI: Distinguished Professor Sang Yup Lee) Project by the Ministry of Science and ICT, and the ‘Development of Protein Production Technology from Inorganic Substances through Microbiological Metabolic System Control’ (PI: Research Professor Kyeong Rok Choi) by the Agricultural Microbiological Project Group at the Rural Development Administration.
2024.03.05 View 3448 -
A Korean research team develops a new clinical candidate for fatty liver disease
A team of Korean researchers have succeeded in developing a new drug candidate for the treatment of non-alcoholic fatty liver disease (NAFLD) acting on peripheral tissues. To date, there has not been an optimal treatment for non-alcoholic steatohepatitis (NASH), and this discovery is expected to set the grounds for the development of new drugs that can safely suppress both liver fat accumulation and liver fibrosis at the same time.
A joint research team led by Professor Jin Hee Ahn from Gwangju Institute of Science and Technology (GIST) and Professor Hail Kim from the KAIST Graduate School of Medical Science and Engineering developed a new chemical that can suppress disease-specific protein (HTR2A) through years of basic research. The team also revealed to have verified its efficacy and safety through preclinical tests (animal tests) at JD Bioscience Inc., a start-up company founded by Professor Ahn.
Although NAFLD has a prevalence rate as high as 20-30%, and about 5% of the global adult population suffers from NASH, there are no commercial drugs targeting them to date. NAFLD is a chronic disease that starts from the fatty liver and progresses into steatohepatitis, fibrosis, cirrhosis, and liver cancer. The mortality rate of patients increases with accompanied cardiovascular diseases and liver-related complications, and appropriate treatment in the early stage is hence necessary.
< Figure 1. Strategy and history of 5HT2A antagonists. Library and rational design for the development of compound 11c as a potent 5HT2A antagonist. Previous research efforts were discontinued due to limited oral absorption and safety. A therapeutic candidate to overcome this problem was identified and phase 1 clinical trials are currently in progress. >
The new synthetic chemical developed by the joint GIST-KAIST research is an innovative drug candidate that shows therapeutic effects on NASH based on a dual action mechanism that inhibits the accumulation of fat in the liver and liver fibrosis by suppressing the serotonin receptor protein 5HT2A.
The research team confirmed its therapeutic effects in animal models for NAFLD and NASH, in which hepatic steatosis and liver fibrosis* caused by fat accumulation in the liver were suppressed simultaneously by 50-70%.
*fibrosis: stiffening of parts of the liver, also used as a major indicator to track the prognosis of steatosis
The research team explained that the material was designed with optimal polarity and lipid affinity to minimize its permeability across the blood-brain barrier. It therefore does not affect the brain, and causes little side effects in the central nervous system (CNS) such as depression and suicidal ideations, while demonstrating excellent inhibition on its target protein present in tissues outside brain (IC50* = 14 nM). The team also demonstrated its superior efficacy in improving liver fibrosis when compared to similar drugs in the phase 3 clinical trial.
*IC50 (half maximal inhibitory concentration): the concentration at which a chemical suppresses 50% of a particular biological function
< Figure 2. GM-60106 (11c)'s effect on obesity: When GM-60106 was administered to an obese animal model (mice) for 2 months, body weight, body fat mass, and blood sugar were significantly reduced (a-d). In addition, the steatohepatitis level (NAFLD Activity Score) and the expression of genes of the treated mice involved in adipogenesis along with blood/liver fat decreased (e-h) >
Based on the pharmacological data obtained through preclinical trials, the team evaluated the effects of the drug on 88 healthy adults as part of their phase 1 clinical trial, where the side effects and the safe dosage of a drug are tested against healthy adults. Results showed no serious side effects and a good level of drug safety.
In addition, a preliminary efficacy evaluation on eight adults with steatohepatitis is currently underway.
Professor Jin Hee Ahn said, “The aim of this research is to develop a treatment for NASH with little side effects and guaranteed safety by developing a new target. The developed chemical is currently going through phase 1 of the global clinical trial in Australia through JD Bioscience Inc., a bio venture company for innovative drug development.” he added, “The candidate material the research team is currently developing shows not only a high level of safety and preventative effects by suppressing fat accumulation in the liver, but also a direct therapeutic effect on liver fibrosis. This is a strength that distinguishes our material from other competing drugs.”
< Figure 3. Efficacy of GM-60106 (11c) on liver fibrosis: When GM-60106 was administered to a steatohepatitis model (mice) for 3 months, the expression of genes associated with tissue fibrosis was significantly reduced (b-c). As a result of a detailed analysis of the tissues of the animal model, it was confirmed that the rate of tissue fibrosis was reduced and the expression rate of genes related to tissue fibrosis and inflammation was also significantly reduced (e-h). >
Professor Hail Kim from KAIST said, “Until now, this disease did not have a method of treatment other than weight control, and there has been no attempt to develop a drug that can be used for non-obese patients.” He added, “Through this research, we look forward to the development of various treatment techniques targeting a range of metabolic diseases including NASH that do not affect the weight of the patient.”
This study, conducted together by the research teams led by Professor Ahn from GIST and Professor Kim from KAIST, as well as the research team from JD Bioscience Inc., was supported by the Ministry of Science and ICT, and the National New Drug Development Project. The results of this research were published by Nature Communications on January 20.
The team also presented the results of their clinical study on the candidate material coded GM-60106 targeting metabolic abnormality-related MASH* at NASH-TAG Conference 2024, which was held in Utah for three days starting on January 4, which was selected as an excellent abstract.
*MASH (Metabolic Dysfunction-Associated Steatohepatitis): new replacement term for NASH
2024.02.21 View 4555 -
Genome Sequencing Unveils Mutational Impacts of Radiation on Mammalian Cells
Recent release of the waste water from Japan's Fukushima nuclear disaster stirred apprehension regarding the health implications of radiation exposure. Classified as a Group 1 carcinogen, ionizing radiation has long been associated with various cancers and genetic disorders, as evidenced by survivors and descendants of atomic bombings and the Chernobyl disaster. Despite much smaller amount, we remain consistently exposed to low levels of radiation in everyday life and medical procedures.
Radiation, whether in the form of high-energy particles or electromagnetic waves, is conventionally known to break our cellular DNA, leading to cancer and genetic disorders. Yet, our understanding of the quantitative and qualitative mutational impacts of ionizing radiation has been incomplete.
On the 14th, Professor Young Seok Ju and his research team from KAIST, in collaboration with Dr. Tae Gen Son from the Dongnam Institute of Radiological and Medical Science, and Professors Kyung Su Kim and Ji Hyun Chang from Seoul National University, unveiled a breakthrough. Their study, led by joint first authors Drs. Jeonghwan Youk, Hyun Woo Kwon, Joonoh Lim, Eunji Kim and Tae-Woo Kim, titled "Quantitative and qualitative mutational impact of ionizing radiation on normal cells," was published in Cell Genomics.
Employing meticulous techniques, the research team comprehensively analyzed the whole-genome sequences of cells pre- and post-radiation exposure, pinpointing radiation-induced DNA mutations. Experiments involving cells from different organs of humans and mice exposed to varying radiation doses revealed mutation patterns correlating with exposure levels. (Figure 1)
Notably, exposure to 1 Gray (Gy) of radiation resulted in on average 14 mutations in every post-exposure cell. (Figure 2) Unlike other carcinogens, radiation-induced mutations primarily comprised short base deletions and a set of structural variations including inversions, translocations, and various complex genomic rearrangements. (Figure 3) Interestingly, experiments subjecting cells to low radiation dose rate over 100 days demonstrated that mutation quantities, under equivalent total radiation doses, mirrored those of high-dose exposure.
"Through this study, we have clearly elucidated the effects of radiation on cells at the molecular level," said Prof. Ju at KAIST. "Now we understand better how radiation changes the DNA of our cells," he added.
Dr. Son from the Dongnam Institute of Radiological and Medical Science stated, "Based on this study, we will continue to research the effects of very low and very high doses of radiation on the human body," and further remarked, "We will advance the development of safe and effective radiation therapy techniques."
Professors Kim and Chang from Seoul National University College of Medicine expressed their views, saying, "Through this study, we believe we now have a tool to accurately understand the impact of radiation on human DNA," and added, "We hope that many subsequent studies will emerge using the research methodologies employed in this study."
This research represents a significant leap forward in radiation studies, made possible through collaborative efforts and interdisciplinary approaches. This pioneering research engaged scholars from diverse backgrounds, spanning from the Genetic Engineering Research Institute at Seoul National University, the Cambridge Stem Cell Institute in the UK, the Institute for Molecular Biotechnology in Austria (IMBA), and the Genome Insight Inc. (a KAIST spin-off start-up). This study was supported by various institutions including the National Research Foundation of Korea, Dongnam Institute of Radiological and Medical Science (supported by Ministry of Science and ICT, the government of South Korea), the Suh Kyungbae Foundation, the Human Frontier Science Program (HFSP), and the Korea University Anam Hospital Korea Foundation for the Advancement of Science and Creativity, the Ministry of Science and ICT, and the National R&D Program.
2024.02.15 View 3851 -
Team KAIST placed among top two at MBZIRC Maritime Grand Challenge
Representing Korean Robotics at Sea: KAIST’s 26-month strife rewarded
Team KAIST placed among top two at MBZIRC Maritime Grand Challenge
- Team KAIST, composed of students from the labs of Professor Jinwhan Kim of the Department of Mechanical Engineering and Professor Hyunchul Shim of the School of Electrical and Engineering, came through the challenge as the first runner-up winning the prize money totaling up to $650,000 (KRW 860 million).
- Successfully led the autonomous collaboration of unmanned aerial and maritime vehicles using cutting-edge robotics and AI technology through to the final round of the competition held in Abu Dhabi from January 10 to February 6, 2024.
KAIST (President Kwang-Hyung Lee), reported on the 8th that Team KAIST, led by students from the labs of Professor Jinwhan Kim of the Department of Mechanical Engineering and Professor Hyunchul Shim of the School of Electrical Engineering, with Pablo Aviation as a partner, won a total prize money of $650,000 (KRW 860 million) at the Maritime Grand Challenge by the Mohamed Bin Zayed International Robotics Challenge (MBZIRC), finishing first runner-up.
This competition, which is the largest ever robotics competition held over water, is sponsored by the government of the United Arab Emirates and organized by ASPIRE, an organization under the Abu Dhabi Ministry of Science, with a total prize money of $3 million.
In the competition, which started at the end of 2021, 52 teams from around the world participated and five teams were selected to go on to the finals in February 2023 after going through the first and second stages of screening. The final round was held from January 10 to February 6, 2024, using actual unmanned ships and drones in a secluded sea area of 10 km2 off the coast of Abu Dhabi, the capital of the United Arab Emirates. A total of 18 KAIST students and Professor Jinwhan Kim and Professor Hyunchul Shim took part in this competition at the location at Abu Dhabi.
Team KAIST will receive $500,000 in prize money for taking second place in the final, and the team’s prize money totals up to $650,000 including $150,000 that was as special midterm award for finalists.
The final mission scenario is to find the target vessel on the run carrying illegal cargoes among many ships moving within the GPS-disabled marine surface, and inspect the deck for two different types of stolen cargo to recover them using the aerial vehicle to bring the small cargo and the robot manipulator topped on an unmanned ship to retrieve the larger one. The true aim of the mission is to complete it through autonomous collaboration of the unmanned ship and the aerial vehicle without human intervention throughout the entire mission process. In particular, since GPS cannot be used in this competition due to regulations, Professor Jinwhan Kim's research team developed autonomous operation techniques for unmanned ships, including searching and navigating methods using maritime radar, and Professor Hyunchul Shim's research team developed video-based navigation and a technology to combine a small autonomous robot with a drone.
The final mission is to retrieve cargo on board a ship fleeing at sea through autonomous collaboration between unmanned ships and unmanned aerial vehicles without human intervention. The overall mission consists the first stage of conducting the inspection to find the target ship among several ships moving at sea and the second stage of conducting the intervention mission to retrieve the cargoes on the deck of the ship. Each team was given a total of three opportunities, and the team that completed the highest-level mission in the shortest time during the three attempts received the highest score.
In the first attempt, KAIST was the only team to succeed in the first stage search mission, but the competition began in earnest as the Croatian team also completed the first stage mission in the second attempt. As the competition schedule was delayed due to strong winds and high waves that continued for several days, the organizers decided to hold the finals with the three teams, including the Team KAIST and the team from Croatia’s the University of Zagreb, which completed the first stage of the mission, and Team Fly-Eagle, a team of researcher from China and UAE that partially completed the first stage. The three teams were given the chance to proceed to the finals and try for the third attempt, and in the final competition, the Croatian team won, KAIST took the second place, and the combined team of UAE-China combined team took the third place. The final prize to be given for the winning team is set at $2 million with $500,000 for the runner-up team, and $250,000 for the third-place.
Professor Jinwhan Kim of the Department of Mechanical Engineering, who served as the advisor for Team KAIST, said, “I would like to express my gratitude and congratulations to the students who put in a huge academic and physical efforts in preparing for the competition over the past two years. I feel rewarded because, regardless of the results, every bit of efforts put into this up to this point will become the base of their confidence and a valuable asset in their growth into a great researcher.” Sol Han, a doctoral student in mechanical engineering who served as the team leader, said, “I am disappointed of how narrowly we missed out on winning at the end, but I am satisfied with the significance of the output we’ve got and I am grateful to the team members who worked hard together for that.”
HD Hyundai, Rainbow Robotics, Avikus, and FIMS also participated as sponsors for Team KAIST's campaign.
2024.02.09 View 6405 -
A KAIST Research Team Develops a Novel “Bone Bandage” Material for Cracked Bones
Bone regeneration is a complex process, and existing methods to aid regeneration including transplants and growth factor transmissions face limitations such as the high cost. But recently, a piezoelectric material that can promote the growth of bone tissue has been developed.
A KAIST research team led by Professor Seungbum Hong from the Department of Materials Science and Engineering (DMSE) announced on January 25 the development of a biomimetic scaffold that generates electrical signals upon the application of pressure by utilizing the unique osteogenic ability of hydroxyapatite (HAp). This research was conducted in collaboration with a team led by Professor Jangho Kim from the Department of Convergence Biosystems Engineering at Chonnam National University.
HAp is a basic calcium phosphate material found in bones and teeth. This biocompatible mineral substance is also known to prevent tooth decay and is often used in toothpaste.
Previous studies on piezoelectric scaffolds confirmed the effects of piezoelectricity on promoting bone regeneration and improving bone fusion in various polymer-based materials, but were limited in simulating the complex cellular environment required for optimal bone tissue regeneration. However, this research suggests a new method for utilizing the unique osteogenic abilities of HAp to develop a material that mimics the environment for bone tissue in a living body.
< Figure 1. Design and characterization of piezoelectrically and topographically originated biomimetic scaffolds. (a) Schematic representation of the enhanced bone regeneration mechanism through electrical and topographical cues provided by HAp-incorporated P(VDF-TrFE) scaffolds. (b) Schematic diagram of the fabrication process. >
The research team developed a manufacturing process that fuses HAp with a polymer film. The flexible and free-standing scaffold developed through this process demonstrated its remarkable potential for promoting bone regeneration through in-vitro and in-vivo experiments in rats.
The team also identified the principles of bone regeneration that their scaffold is based on. Using atomic force microscopy (AFM), they analysed the electrical properties of the scaffold and evaluated the detailed surface properties related to cell shape and cell skeletal protein formation. They also investigated the effects of piezoelectricity and surface properties on the expression of growth factors.
Professor Hong from KAIST’s DMSE said, “We have developed a HAp-based piezoelectric composite material that can act like a ‘bone bandage’ through its ability to accelerate bone regeneration.” He added, “This research not only suggests a new direction for designing biomaterials, but is also significant in having explored the effects of piezoelectricity and surface properties on bone regeneration.”
This research, conducted by co-first authors Soyun Joo and Soyeon Kim from Professor Hong’s group, was published on ACS Applied Materials & Interfaces on January 4 under the title “Piezoelectrically and Topographically Engineered Scaffolds for Accelerating Bone Regeneration”. From Professor Kim’s group, Ph.D. candidate Yonghyun Gwon also participated as co-first author, and Professor Kim himself as a corresponding author.
< Figure 2. Analysis of piezoelectric and surface properties of the biomimetic scaffolds using atomic force microscopy. (a) PFM amplitude and phase images of box-poled composite scaffolds. The white bar represents 2 μm. (b) 3D representations of composite scaffolds paired with typical 2D line sections. (c) In vivo bone regeneration micro-CT analysis, (d) schematic representation of filler-derived electrical origins in bone regeneration. >
This research was supported by the KAIST Research and Development Team, the KUSTAR-KAIST Joint Research Center, the KAIST Global Singularity Project, and the government-funded Basic Research Project by the National Research Foundation of Korea.
2024.02.01 View 4218 -
KAIST Research Team Develops Sweat-Resistant Wearable Robot Sensor
New electromyography (EMG) sensor technology that allows the long-term stable control of wearable robots and is not affected by the wearer’s sweat and dead skin has gained attention recently. Wearable robots are devices used across a variety of rehabilitation treatments for the elderly and patients recovering from stroke or trauma.
A joint research team led by Professor Jae-Woong Jung from the KAIST School of Electrical Engineering (EE) and Professor Jung Kim from the KAIST Department of Mechanical Engineering (ME) announced on January 23rd that they have successfully developed a stretchable and adhesive microneedle sensor that can electrically sense physiological signals at a high level without being affected by the state of the user’s skin.
For wearable robots to recognize the intentions behind human movement for their use in rehabilitation treatment, they require a wearable electrophysiological sensor that gives precise EMG measurements. However, existing sensors often show deteriorating signal quality over time and are greatly affected by the user’s skin conditions. Furthermore, the sensor’s higher mechanical hardness causes noise since the contact surface is unable to keep up with the deformation of the skin. These shortcomings limit the reliable, long-term control of wearable robots.
< Figure 1. Design and working concept of the Stretchable microNeedle Adhesive Patch (SNAP). (A) Schematic illustration showing the overall system configuration and application of SNAP. (B) Exploded view schematic diagram of a SNAP, consisting of stretchable serpentine interconnects, Au-coated Si microneedle, and ECA made of Ag flakes–silicone composite. (C) Optical images showing high mechanical compliance of SNAP. >
However, the recently developed technology is expected to allow long-term and high-quality EMG measurements as it uses a stretchable and adhesive conducting substrate integrated with microneedle arrays that can easily penetrate the stratum corneum without causing discomfort. Through its excellent performance, the sensor is anticipated to be able to stably control wearable robots over a long period of time regardless of the wearer’s changing skin conditions and without the need for a preparation step that removes sweat and dead cells from the surface of their skin.
The research team created a stretchable and adhesive microneedle sensor by integrating microneedles into a soft silicon polymer substrate. The hard microneedles penetrate through the stratum corneum, which has high electrical resistance. As a result, the sensor can effectively lower contact resistance with the skin and obtain high-quality electrophysiological signals regardless of contamination. At the same time, the soft and adhesive conducting substrate can adapt to the skin’s surface that stretches with the wearer’s movement, providing a comfortable fit and minimizing noise caused by movement.
< Figure 2. Demonstration of the wireless Stretchable microNeedle Adhesive Patch (SNAP) system as an Human-machine interfaces (HMI) for closed-loop control of an exoskeleton robot. (A) Illustration depicting the system architecture and control strategy of an exoskeleton robot. (B) The hardware configuration of the pneumatic back support exoskeleton system. (C) Comparison of root mean square (RMS) of electromyography (EMG) with and without robotic assistance of pretreated skin and non-pretreated skin. >
To verify the usability of the new patch, the research team conducted a motion assistance experiment using a wearable robot. They attached the microneedle patch on a user’s leg, where it could sense the electrical signals generated by the muscle. The sensor then sent the detected intention to a wearable robot, allowing the robot to help the wearer lift a heavy object more easily.
Professor Jae-Woong Jung, who led the research, said, “The developed stretchable and adhesive microneedle sensor can stability detect EMG signals without being affected by the state of a user’s skin. Through this, we will be able to control wearable robots with higher precision and stability, which will help the rehabilitation of patients who use robots.”
The results of this research, written by co-first authors Heesoo Kim and Juhyun Lee, who are both Ph.D. candidates in the KAIST School of EE, were published in Science Advances on January 17th under the title “Skin-preparation-free, stretchable microneedle adhesive patches for reliable electrophysiological sensing and exoskeleton robot control”.
This research was supported by the Bio-signal Sensor Integrated Technology Development Project by the National Research Foundation of Korea, the Electronic Medicinal Technology Development Project, and the Step 4 BK21 Project.
2024.01.30 View 4082 -
KAIST Research team develops anti-icing film that only requires sunlight
A KAIST research team has developed an anti-icing and de-icing film coating technology that can apply the photothermal effect of gold nanoparticles to industrial sites without the need for heating wires, periodic spray or oil coating of anti-freeze substances, and substrate design alterations.
The group led by Professor Hyoungsoo Kim from the Department of Mechanical Engineering (Fluid & Interface Laboratory) and Professor Dong Ki Yoon from the Department of Chemistry (Soft Material Assembly Group) revealed on January 3 to have together developed an original technique that can uniformly pattern gold nanorod (GNR) particles in quadrants through simple evaporation, and have used this to develop an anti-icing and de-icing surface.
Many scientists in recent years have tried to control substrate surfaces through various coating techniques, and those involving the patterning of functional nanomaterials have gained special attention. In particular, GNR is considered a promising candidate nanomaterial for its biocompatibility, chemical stability, relatively simple synthesis, and its stable and unique property of surface plasmon resonance. To maximize the performance of GNR, it is important to achieve a high uniformity during film deposition, and a high level of rod alignment. However, achieving both criteria has thus far been a difficult challenge.
< Figure 1. Conceptual image to display Hydrodynamic mechanisms for the formation of a homogeneous quadrant cellulose nanocrystal(CNC) matrix. >
To solve this, the joint research team utilized cellulose nanocrystal (CNC), a next-generation functional nanomaterial that can easily be extracted from nature. By co-assembling GNR on CNC quadrant templates, the team could uniformly dry the film and successfully obtain a GNR film with a uniform alignment in a ring-shape. Compared to existing coffee-ring films, the highly uniform and aligned GNR film developed through this research showed enhanced plasmonic photothermal properties, and the team showed that it could carry out anti-icing and de-icing functions by simply irradiating light in the visible wavelength range.
< Figure 2. Optical and thermal performance evaluation results of gold nanorod film and demonstration of plasmonic heater for anti-icing and de-icing. >
Professor Hyoungsoo Kim said, “This technique can be applied to plastic, as well as flexible surfaces. By using it on exterior materials and films, it can generate its own heat energy, which would greatly save energy through voluntary thermal energy harvesting across various applications including cars, aircrafts, and windows in residential or commercial spaces, where frosting becomes a serious issue in the winter.” Professor Dong Ki Yoon added, “This research is significant in that we can now freely pattern the CNC-GNR composite, which was previously difficult to create into films, over a large area. We can utilize this as an anti-icing material, and if we were to take advantage of the plasmonic properties of gold, we can also use it like stained-glass to decorate glass surfaces.”
This research was conducted by Ph.D. candidate Jeongsu Pyeon from the Department of Mechanical Engineering, and his co-first author Dr. Soon Mo Park (a KAIST graduate, currently a post-doctoral associate at Cornell University), and was pushed in the online volume of Nature Communication on December 8, 2023 under the title “Plasmonic Metasurfaces of Cellulose Nanocrystal Matrices with Quadrants of Aligned Gold Nanorods for Photothermal Anti-Icing." Recognized for its achievement, the research was also selected as an editor’s highlight for the journals Materials Science and Chemistry, and Inorganic and Physical Chemistry.
This research was supported by the Individual Basic Mid-Sized Research Fund from the National Research Foundation of Korea and the Center for Multiscale Chiral Architectures.
2024.01.16 View 6291