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KAIST Succeeds in the Real-time Observation of Organoids using Holotomography
Organoids, which are 3D miniature organs that mimic the structure and function of human organs, play an essential role in disease research and drug development. A Korean research team has overcome the limitations of existing imaging technologies, succeeding in the real-time, high-resolution observation of living organoids.
KAIST (represented by President Kwang Hyung Lee) announced on the 14th of October that Professor YongKeun Park’s research team from the Department of Physics, in collaboration with the Genome Editing Research Center (Director Bon-Kyoung Koo) of the Institute for Basic Science (IBS President Do-Young Noh) and Tomocube Inc., has developed an imaging technology using holotomography to observe live, small intestinal organoids in real time at a high resolution.
Existing imaging techniques have struggled to observe living organoids in high resolution over extended periods and often required additional treatments like fluorescent staining.
< Figure 1. Overview of the low-coherence HT workflow. Using holotomography, 3D morphological restoration and quantitative analysis of organoids can be performed. In order to improve the limited field of view, which is a limitation of the microscope, our research team utilized a large-area field of view combination algorithm and made a 3D restoration by acquiring multi-focus holographic images for 3D measurements. After that, the organoids were compartmentalized to divide the parts necessary for analysis and quantitatively evaluated the protein concentration measurable from the refractive index and the survival rate of the organoids. >
The research team introduced holotomography technology to address these issues, which provides high-resolution images without the need for fluorescent staining and allows for the long-term observation of dynamic changes in real time without causing cell damage.
The team validated this technology using small intestinal organoids from experimental mice and were able to observe various cell structures inside the organoids in detail. They also captured dynamic changes such as growth processes, cell division, and cell death in real time using holotomography.
Additionally, the technology allowed for the precise analysis of the organoids' responses to drug treatments, verifying the survival of the cells.
The researchers believe that this breakthrough will open new horizons in organoid research, enabling the greater utilization of organoids in drug development, personalized medicine, and regenerative medicine.
Future research is expected to more accurately replicate the in vivo environment of organoids, contributing significantly to a more detailed understanding of various life phenomena at the cellular level through more precise 3D imaging.
< Figure 2. Real-time organoid morphology analysis. Using holotomography, it is possible to observe the lumen and villus development process of intestinal organoids in real time, which was difficult to observe with a conventional microscope. In addition, various information about intestinal organoids can be obtained by quantifying the size and protein amount of intestinal organoids through image analysis. >
Dr. Mahn Jae Lee, a graduate of KAIST's Graduate School of Medical Science and Engineering, currently at Chungnam National University Hospital and the first author of the paper, commented, "This research represents a new imaging technology that surpasses previous limitations and is expected to make a major contribution to disease modeling, personalized treatments, and drug development research using organoids."
The research results were published online in the international journal Experimental & Molecular Medicine on October 1, 2024, and the technology has been recognized for its applicability in various fields of life sciences. (Paper title: “Long-term three-dimensional high-resolution imaging of live unlabeled small intestinal organoids via low-coherence holotomography”)
This research was supported by the National Research Foundation of Korea, KAIST Institutes, and the Institute for Basic Science.
2024.10.14 View 987 -
KAIST Changes the Paradigm of Drug Discovery with World's First Atomic Editing
In pioneering drug development, the new technology that enables the easy and rapid editing of key atoms responsible for drug efficacy has been regarded as a fundamental and "dream" technology, revolutionizing the process of discovering potential drug candidates. KAIST researchers have become the first in the world to successfully develop single-atom editing technology that maximizes drug efficacy.
On October 8th, KAIST (represented by President Kwang-Hyung Lee) announced that Professor Yoonsu Park’s research team from the Department of Chemistry successfully developed technology that enables the easy editing and correction of oxygen atoms in furan compounds into nitrogen atoms, directly converting them into pyrrole frameworks, which are widely used in pharmaceuticals.
< Image. Conceptual image illustrating the main idea of the research >
This research was published in the prestigious scientific journal Science on October 3rd under the title "Photocatalytic Furan-to-Pyrrole Conversion."
Many drugs have complex chemical structures, but their efficacy is often determined by a single critical atom. Atoms like oxygen and nitrogen play a central role in enhancing the pharmacological effects of these drugs, particularly against viruses.
This phenomenon, where the introduction of specific atoms into a drug molecule dramatically affects its efficacy, is known as the "Single Atom Effect." In leading-edge drug development, discovering atoms that maximize drug efficacy is key.
However, evaluating the Single Atom Effect has traditionally required multi-step, costly synthesis processes, as it has been difficult to selectively edit single atoms within stable ring structures containing oxygen or nitrogen.
Professor Park’s team overcame this challenge by introducing a photocatalyst that uses light energy. They developed a photocatalyst that acts as a “molecular scissor,” freely cutting and attaching five-membered rings, enabling single-atom editing at room temperature and atmospheric pressure—a world first.
The team discovered a new reaction mechanism in which the excited molecular scissor removes oxygen from furan via single-electron oxidation and then sequentially adds a nitrogen atom.
Donghyeon Kim and Jaehyun You, the study's first authors and candidates in KAIST’s integrated master's and doctoral program in the Department of Chemistry, explained that this technique offers high versatility by utilizing light energy to replace harsh conditions. They further noted that the technology enables selective editing, even when applied to complex natural products or pharmaceuticals. Professor Yoonsu Park, who led the research, remarked, "This breakthrough, which allows for the selective editing of five-membered organic ring structures, will open new doors for building libraries of drug candidates, a key challenge in pharmaceuticals. I hope this foundational technology will be used to revolutionize the drug development process."
The significance of this research was highlighted in the Perspective section of Science, a feature where a peer scientist of prominence outside of the project group provides commentary on an impactful research.
This research was supported by the National Research Foundation of Korea’s Creative Research Program, the Cross-Generation Collaborative Lab Project at KAIST, and the POSCO Science Fellowship of the POSCO TJ Park Foundation.
2024.10.11 View 1562 -
KAIST Develops Stretchable Displays Featuring 25% Expansion Without Image Distortion
Stretchable displays, praised for their spatial efficiency, design flexibility, and human-like flexibility, are seen as the next generation of display technology. A team of Korean researchers has developed a stretchable display that can expand by 25% while maintaining clear image quality without distortion. It can also stretch and contract up to 5,000 times at 15% expansion without any performance degradation, making it the first deformation-free stretchable display with a negative Poisson's ratio* developed in Korea.
*Poisson’s ratio of -1: A ratio where both width and length stretch equally, expressed as a negative value. A positive Poisson's ratio represents the ratio where horizontal stretching leads to vertical contraction, which is the case for most materials.
KAIST (represented by President Kwang-Hyung Lee) announced on the 20th of August that a research team led by Professor Byeong-Soo Bae of the Department of Materials Science and Engineering (Director of the Wearable Platform Materials Technology Center) , in collaboration with the Korea Institute of Machinery & Materials (President Seoghyeon Ryu), successfully developed a stretchable display substrate that suppresses image distortion through omnidirectional stretchability.
Currently, most stretchable displays are made with highly elastic elastomer* materials, but these materials possess a positive Poisson's ratio, causing unavoidable image distortion when the display is stretched.
*Elastomer: A polymer with elasticity similar to rubber.
To address this, the introduction of auxetic* meta-structures has been gaining attention. Unlike conventional materials, auxetic structures have a unique 'negative Poisson's ratio,' expanding in all directions when stretched in just one direction. However, traditional auxetic structures contain many empty spaces, limiting their stability and usability in display substrates.
*Auxetic structure: A special geometric structure that exhibits a negative Poisson's ratio.
To tackle the issue of image distortion, Professor Bae's research team developed a method to create a seamless surface for the auxetic meta-structure, achieving the ideal negative Poisson's ratio of -1 and overcoming the biggest challenge in auxetic meta-structures.
To overcome the second issue of elastic modulus*, the team inserted a textile made of glass fiber bundles with a diameter of just 25 micrometers (a quarter of the thickness of human hair) into the elastomer material. They then filled the empty spaces with the same elastomer, creating a flat and stable integrated film without gaps.
*Elastic Modulus: The ratio that indicates the extent of deformation when force is applied to a material. A higher elastic modulus means that the material is less likely to deform under force.
The research team theoretically identified that the difference in elasticity between the auxetic structure and the elastomer material directly influences the negative Poisson's ratio and successfully achieved an elasticity difference of over 230,000 times, producing a film with a Poisson's ratio of -1, the theoretical limit.
< Figure 2. Deformation of S-AUX film. a) Configurations and visualized principal strain distribution of the optimized S-AUX film at various strain rates. b) Biaxial stretching image. While pristine elastomer shrinks in the directions that were not stretched, S-AUX film developed in this study expands in all directions simultaneously while maintaining its original shape. >
Professor Byeong-Soo Bae, who led the study, explained, "Preventing image distortion using auxetic structures in stretchable displays is a core technology, but it has faced challenges due to the many empty spaces in the surface, making it difficult to use as a substrate. This research outcome is expected to significantly accelerate commercialization through high-resolution, distortion-free stretchable display applications that utilize the entire surface."
This study, co-authored by Dr. Yung Lee from KAIST’s Department of Materials Science and Engineering and Dr. Bongkyun Jang from the Korea Institute of Machinery & Materials, was published on August 20th in the international journal Nature Communications under the title "A seamless auxetic substrate with a negative Poisson's ratio of –1".
The research was supported by the Wearable Platform Materials Technology Center at KAIST, the Korea Institute of Machinery & Materials, and LG Display.
< Figure 3. Structural configuration of the distortion-free display components on the S-AUX film and a contour image of a micro-LED chip transferred onto the S-AUX film. >
< Figure 4. Schematic illustrations and photographic images of the S-AUX film-based image: distortion-free display in its stretched state and released state. >
2024.09.20 View 2224 -
KAIST finds ways for Bacteria to produce PET-like materials
Among various eco-friendly polymers, polyhydroxyalkanoates (PHA) stand out for their excellent biodegradability and biocompatibility. They decompose naturally in soil and marine environments and are used in applications such as food packaging and medical products. However, natural PHA produced to date has faced challenges meeting various physical property requirements, such as durability and thermal stability, and has been limited in its commercial application due to low production concentrations. In light of this, KAIST researchers have recently developed a technology that could play a crucial role in solving the environmental pollution problem caused by plastics.
KAIST (represented by President Kwang-Hyung Lee) announced on August 26th that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering, including Dr. Youngjoon Lee and master's student Minju Kang, has successfully developed a microbial strain that efficiently produces aromatic polyester* using systems metabolic engineering.
※ Aromatic polyester: A polymer containing aromatic compounds (specific carbon ring structures like benzene) and ester bonds.
In this study, the research team used metabolic engineering to enhance the metabolic flux of the biosynthetic pathway for the aromatic monomer phenyllactate (PhLA) in E. coli. They manipulated the metabolic pathway to increase the polymer fraction accumulated within the cells and employed computer simulations to predict the structure of PHA synthase and improve the enzyme based on the structure-function relationship.
Through subsequent fermentation optimization, the team achieved the world’s highest concentration (12.3±0.1 g/L) for the efficient production of poly (PhLA) and successfully produced polyester through a 30L scale fed-batch fermentation, demonstrating the possibility of industrial-level production. The produced aromatic polyesters showed enhanced thermal properties, improved mechanical properties, and potential for use as drug delivery carriers.
< Figure 1. Development schematics of aromatic polyester producing microorganisms >
The research team also demonstrated that an exogenous phasin protein* plays a crucial role in increasing the intracellular polymer accumulation fraction, which is directly related to the economic feasibility and efficiency of non-natural PHA production. They improved PHA synthase using a rational enzyme design approach, predicting the three-dimensional structure of the enzyme through homology modeling (a method of predicting the three-dimensional structure of a new protein based on the structure of similar proteins) followed by molecular docking simulations (simulations that predict how well a monomer can bind to an enzyme) and molecular dynamics simulations (simulations that predict how molecules move and interact over time) to upgrade the enzyme into a mutant enzyme with enhanced monomer polymerization efficiency.
※ Exogenous phasin protein: Phasin is a protein related to PHA production, interacting with the cytoplasmic environment on the surface of granules of PHA, and playing a role in polymer accumulation and controlling the number and size of granules. In this study, genes encoding phasin proteins derived from various natural PHA-producing microorganisms were selected and introduced.
Dr. Youngjoon Lee, co-first author of the paper, explained, "The significance of this study lies in the fact that we have achieved the world's highest concentration of microbial-based aromatic polyester production using eco-friendly materials and methods. This technology is expected to play a crucial role in addressing the environmental pollution caused by plastics." Distinguished Professor Sang Yup Lee added, "This study, which presents various strategies for the high-efficiency production of useful polymers via systems metabolic engineering, is expected to make a significant contribution to solving climate change issues, particularly the recent plastic problem."
< Figure 2. Detailed development strategy for aromatic polyester producing microorganisms >
The research findings were published on August 21st in Trends in Biotechnology, published by Cell, an international academic journal.
※ Paper Title: “Microbial production of an aromatic homopolyester”
※ Author Information: Youngjoon Lee (KAIST, co-first author), Minju Kang (KAIST, co-first author), Woo Dae Jang (KAIST, second author), So Young Choi (KAIST, third author), Jung Eun Yang (KAIST, fourth author), Sang Yup Lee (KAIST, corresponding author), totaling six authors.
This research was supported by the "Development of Next-Generation Biorefinery Platform Technologies for Leading the Bio-based Chemicals Industry" project led by Distinguished Professor Sang Yup Lee at KAIST, under the eco-friendly chemical technology development project aimed at substituting petroleum, funded by the Ministry of Science and ICT. It was also supported by the "Development of Platform Technology for the Production of Novel Aromatic Bioplastic Using Microbial Cell Factories" project (Project Leader: Si Jae Park, Ewha Woman’s University).
2024.08.28 View 2025 -
KAIST presents strategies for Holotomography in advanced bio research
Measuring and analyzing three-dimensional (3D) images of live cells and tissues is considered crucial in advanced fields of biology and medicine. Organoids, which are 3D structures that mimic organs, are particular examples that significantly benefits 3D live imaging. Organoids provide effective alternatives to animal testing in the drug development processes, and can rapidly determine personalized medicine. On the other hand, active researches are ongoing to utilize organoids for organ replacement.
< Figure 1. Schematic illustration of holotomography compared to X-ray CT. Similar to CT, they share the commonality of measuring the optical properties of an unlabeled specimen in three dimensions. Instead of X-rays, holotomography irradiates light in the visible range, and provides refractive index measurements of transparent specimens rather than absorptivity. While CT obtains three-dimensional information only through mechanical rotation of the irradiating light, holotomography can replace this by applying wavefront control technology in the visible range. >
Organelle-level observation of 3D biological specimens such as organoids and stem cell colonies without staining or preprocessing holds significant implications for both innovating basic research and bioindustrial applications related to regenerative medicine and bioindustrial applications.
Holotomography (HT) is a 3D optical microscopy that implements 3D reconstruction analogous to that of X-ray computed tomography (CT). Although HT and CT share a similar theoretical background, HT facilitates high-resolution examination inside cells and tissues, instead of the human body. HT obtains 3D images of cells and tissues at the organelle level without chemical or genetic labeling, thus overcomes various challenges of existing methods in bio research and industry. Its potential is highlighted in research fields where sample physiology must not be disrupted, such as regenerative medicine, personalized medicine, and infertility treatment.
< Figure 2. Label-free 3D imaging of diverse live cells. Time-lapse image of Hep3B cells illustrating subcellular morphology changes upon H2O2 treatment, followed by cellular recovery after returning to the regular cell culture medium. >
This paper introduces the advantages and broad applicability of HT to biomedical researchers, while presenting an overview of principles and future technical challenges to optical researchers. It showcases various cases of applying HT in studies such as 3D biology, regenerative medicine, and cancer research, as well as suggesting future optical development. Also, it categorizes HT based on the light source, to describe the principles, limitations, and improvements of each category in detail. Particularly, the paper addresses strategies for deepening cell and organoid studies by introducing artificial intelligence (AI) to HT.
Due to its potential to drive advanced bioindustry, HT is attracting interest and investment from universities and corporates worldwide. The KAIST research team has been leading this international field by developing core technologies and carrying out key application researches throughout the last decade.
< Figure 3. Various types of cells and organelles that make up the imaging barrier of a living intestinal organoid can be observed using holotomography. >
This paper, co-authored by Dr. Geon Kim from KAIST Research Center for Natural Sciences, Professor Ki-Jun Yoon's team from the Department of Biological Sciences, Director Bon-Kyoung Koo's team from the Institute for Basic Science (IBS) Center for Genome Engineering, and Dr. Seongsoo Lee's team from the Korea Basic Science Institute (KBSI), was published in 'Nature Reviews Methods Primers' on the 25th of July. This research was supported by the Leader Grant and Basic Science Research Program of the National Research Foundation, the Hologram Core Technology Development Grant of the Ministry of Science and ICT, the Nano and Material Technology Development Project, and the Health and Medical R&D Project of the Ministry of Health and Welfare.
2024.07.30 View 1634 -
Unraveling Mitochondrial DNA Mutations in Human Cells
Throughout our lifetime, cells accumulate DNA mutations, which contribute to genetic diversity, or “mosaicism”, among cells. These genomic mutations are pivotal for the aging process and the onset of various diseases, including cancer. Mitochondria, essential cellular organelles involved in energy metabolism and apoptosis, possess their own DNA, which are susceptible to mutations. However, studies on mtDNA mutations and mosaicism have been limited due to a variety of technical challenges.
Genomic scientists from KAIST have revealed the genetic mosaicism characterized by variations in mitochondrial DNA (mtDNA) across normal human cells. This study provides fundamental insights into understanding human aging and disease onset mechanisms.
The study, “Mitochondrial DNA mosaicism in normal human somatic cells,” was published in Nature Genetics on July 22. It was led by graduate student Jisong An under the supervision of Professor Young Seok Ju from the Graduate School of Medical Science and Engineering.
Researchers from Seoul National University College of Medicine, Yonsei University College of Medicine, Korea University College of Medicine, Washington University School of Medicine National Cancer Center, Seoul National University Hospital, Gangnam Severance Hospital and KAIST faculty startup company Inocras Inc. also participated in this study.
< Figure 1. a. Flow of experiment. b. Schematic diagram illustrating the origin and dynamics of mtDNA alterations across a lifetime. >
The study involved a bioinformatic analysis of whole-genome sequences from 2,096 single cells obtained from normal human colorectal epithelial tissue, fibroblasts, and blood collected from 31 individuals. The study highlights an average of three significant mtDNA differences between cells, with approximately 6% of these variations confirmed to be inherited as heteroplasmy from the mother.
Moreover, mutations significantly increased during tumorigenesis, with some mutations contributing to instability in mitochondrial RNA. Based on these findings, the study illustrates a computational model that comprehensively elucidates the evolution of mitochondria from embryonic development to aging and tumorigenesis.
This study systematically reveals the mechanisms behind mitochondrial DNA mosaicism in normal human cells, establishing a crucial foundation for understanding the impact of mtDNA on aging and disease onset.
Professor Ju remarked, “By systematically utilizing whole-genome big data, we can illuminate previously unknown phenomena in life sciences.” He emphasized the significance of the study, adding, “For the first time, we have established a method to systematically understand mitochondrial DNA changes occurring during human embryonic development, aging, and cancer development.”
This work was supported by the National Research Foundation of Korea and the Suh Kyungbae Foundation.
2024.07.24 View 1965 -
KAIST Develops Microbial Liquid Egg Substitute
A team of researchers published a paper on developing a substitute for eggs using microorganisms, grabbing international attention. It is expected that the development of egg substitutes using non-animal raw materials will solve the problems of factory farming, which causes problems like increased emission of greenhouse gas and waste, and contribute to building a sustainable food system that allows easy protein intake.
KAIST (President Kwang-Hyung Lee) announced that Research Professor Kyeong Rok Choi from the Biological Process Research Center and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering have published a paper on the development of an "Eco-Friendly Liquid Egg Substitute Derived from Microorganisms."
Eggs play a crucial role in various culinary applications due to their unique physicochemical properties such as gelling, foaming, and emulsifying, while also providing essential nutrients. However, traditional egg production is not only unethical and resource-intensive but also has significant environmental impacts such as greenhouse gas emissions and waste issues. Additionally, factors such as wars and trade regulations have led to significant increases in egg prices, highlighting food security concerns. In response to these issues, there has been growing interest in egg substitutes made from non-animal sources to establish a sustainable food system.
Although there has been progress in developing non-animal protein-based egg substitutes, no substitute has been able to fully replicate the essential functional properties of liquid eggs, such as gelling and foaming, while also providing complete nutrition. In this context, the research team aimed to develop a liquid egg substitute using microbial biomass, which has a protein content comparable to that of meat per unit dry mass. Various microorganisms, such as yeast, Bacillus, lactic acid bacteria, and other probiotics, have been proven safe through long-term human consumption. Microbial biomass requires fewer resources like water and land during production, and possesses high-quality nutrients, making it a promising sustainable food resource.
< Figure 1. Comparison of heat treatment results of microbial pellets and microbial lysates >
However, the semi-solid microbial biomass recovered through microbial cultivation was observed to turn liquid upon heating, unlike liquid egg. To address this, the research team devised a microbial lysate by breaking down the cell walls and cell membranes of microorganisms, which correspond to the eggshell. They found that the microbial lysate's proteins coagulated when heated and formed a gel similar to that of liquid egg. The gel formed from the heated microbial lysate was found to have microscopic structures and physical properties similar to those of boiled eggs. The addition of microbial-derived edible enzymes or plant-based materials allowed for the adjustment of its properties, enabling the creation of various textures.
Furthermore, the researchers demonstrated that the microbial lysate could form stable foams widely used in baking, such as meringues (made from egg whites). They successfully baked meringue cookies using this lysate, showing its potential as a functional liquid egg substitute.
Distinguished Professor Sang Yup Lee stated, "This substitute has excellent nutritional components, making it suitable for regular food consumption. It is especially promising as emergency food for long-term space travel, wartime situations, and other emergencies. More importantly, it contributes to securing a sustainable food system."
< Figure 2. Example of foaming ability of microbial lysate and meringue cookie production >
< Figure 3. Example of foaming ability of microbial lysate and meringue cookie production >
The paper was published online in the journal npj Science of Food, issued by Nature.
- Paper Title: Microbial lysates repurposed as liquid egg substitutes
- Authors: Kyeong Rok Choi (first author), Da-Hee Ahn, Seok Yeong Jung, YuHyun Lee, and Sang Yup Lee (corresponding author)
This research was supported by the Ministry of Science and ICT's project for developing eco-friendly chemical technologies to replace petroleum (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) and the Rural Development Administration's Agricultural Microorganisms Project Group (Director: Professor Pan-sik Jang, Seoul National University) for developing protein production technology from inorganic substances through microbial metabolic system control (Project Leader: Research Professor Kyeong Rok Choi, KAIST).
2024.07.05 View 3372 -
KAIST Employs Image-recognition AI to Determine Battery Composition and Conditions
An international collaborative research team has developed an image recognition technology that can accurately determine the elemental composition and the number of charge and discharge cycles of a battery by examining only its surface morphology using AI learning.
KAIST (President Kwang-Hyung Lee) announced on July 2nd that Professor Seungbum Hong from the Department of Materials Science and Engineering, in collaboration with the Electronics and Telecommunications Research Institute (ETRI) and Drexel University in the United States, has developed a method to predict the major elemental composition and charge-discharge state of NCM cathode materials with 99.6% accuracy using convolutional neural networks (CNN)*.
*Convolutional Neural Network (CNN): A type of multi-layer, feed-forward, artificial neural network used for analyzing visual images.
The research team noted that while scanning electron microscopy (SEM) is used in semiconductor manufacturing to inspect wafer defects, it is rarely used in battery inspections. SEM is used for batteries to analyze the size of particles only at research sites, and reliability is predicted from the broken particles and the shape of the breakage in the case of deteriorated battery materials.
The research team decided that it would be groundbreaking if an automated SEM can be used in the process of battery production, just like in the semiconductor manufacturing, to inspect the surface of the cathode material to determine whether it was synthesized according to the desired composition and that the lifespan would be reliable, thereby reducing the defect rate.
< Figure 1. Example images of true cases and their grad-CAM overlays from the best trained network. >
The researchers trained a CNN-based AI applicable to autonomous vehicles to learn the surface images of battery materials, enabling it to predict the major elemental composition and charge-discharge cycle states of the cathode materials. They found that while the method could accurately predict the composition of materials with additives, it had lower accuracy for predicting charge-discharge states. The team plans to further train the AI with various battery material morphologies produced through different processes and ultimately use it for inspecting the compositional uniformity and predicting the lifespan of next-generation batteries.
Professor Joshua C. Agar, one of the collaborating researchers of the project from the Department of Mechanical Engineering and Mechanics of Drexel University, said, "In the future, artificial intelligence is expected to be applied not only to battery materials but also to various dynamic processes in functional materials synthesis, clean energy generation in fusion, and understanding foundations of particles and the universe."
Professor Seungbum Hong from KAIST, who led the research, stated, "This research is significant as it is the first in the world to develop an AI-based methodology that can quickly and accurately predict the major elemental composition and the state of the battery from the structural data of micron-scale SEM images. The methodology developed in this study for identifying the composition and state of battery materials based on microscopic images is expected to play a crucial role in improving the performance and quality of battery materials in the future."
< Figure 2. Accuracies of CNN Model predictions on SEM images of NCM cathode materials with additives under various conditions. >
This research was conducted by KAIST’s Materials Science and Engineering Department graduates Dr. Jimin Oh and Dr. Jiwon Yeom, the co-first authors, in collaboration with Professor Josh Agar and Dr. Kwang Man Kim from ETRI. It was supported by the National Research Foundation of Korea, the KAIST Global Singularity project, and international collaboration with the US research team. The results were published in the international journal npj Computational Materials on May 4. (Paper Title: “Composition and state prediction of lithium-ion cathode via convolutional neural network trained on scanning electron microscopy images”)
2024.07.02 View 2654 -
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 3670 -
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 3999 -
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 2761 -
KAIST Develops Sodium Battery Capable of Rapid Charging in Just a Few Seconds
Sodium (Na), which is over 500 times more abundant than lithium (Li), has recently garnered significant attention for its potential in sodium-ion battery technologies. However, existing sodium-ion batteries face fundamental limitations, including lower power output, constrained storage properties, and longer charging times, necessitating the development of next-generation energy storage materials.
On the 11th of April, KAIST (represented by President Kwang Hyung Lee) announced that a research team led by Professor Jeung Ku Kang from the Department of Materials Science and Engineering had developed a high-energy, high-power hybrid sodium-ion battery capable of rapid charging.
The innovative hybrid energy storage system integrates anode materials typically used in batteries with cathodes suitable for supercapacitors. This combination allows the device to achieve both high storage capacities and rapid charge-discharge rates, positioning it as a viable next-generation alternative to lithium-ion batteries.
However, the development of a hybrid battery with high energy and high power density requires an improvement to the slow energy storage rate of battery-type anodes as well as the enhancement of the relatively low capacity of supercapacitor-type cathode materials.
< Figure 1. Schematic synthetic procedures of high-capacity/high-rate anode and cathode materials for a sodium-ion hybrid energy storages (SIHES) and their proposed energy storage mechanisms. Synthetic procedures for (a) ultrafine iron sulfide-embedded S-doped carbon/graphene (FS/C/G) anode and (b) zeolitic imidazolate framework-derived porous carbon (ZDPC) cathode materials. (c) Proposed energy storage mechanisms of Na+ ions in FS/C/G anode and ClO-4 ions in ZDPC cathode for an SIHES. >
To account for this, Professor Kang's team utilized two distinct metal-organic frameworks for the optimized synthesis of hybrid batteries. This approach led to the development of an anode material with improved kinetics through the inclusion of fine active materials in porous carbon derived from metal-organic frameworks. Additionally, a high-capacity cathode material was synthesized, and the combination of the cathode and anode materials allowed for the development of a sodium-ion storage system optimizing the balance and minimizing the disparities in energy storage rates between the electrodes.
The assembled full cell, comprising the newly developed anode and cathode, forms a high-performance hybrid sodium-ion energy storage device. This device surpasses the energy density of commercial lithium-ion batteries and exhibits the characteristics of supercapacitors' power density. It is expected to be suitable for rapid charging applications ranging from electric vehicles to smart electronic devices and aerospace technologies.
< Figure 2. Electrochemical characterizations of FS/C/G-20//ZDPC SIHES full cells (left). Ragone plots for FS/C/G-20//ZDPC (this work) and other previously reported sodium-ion electrochemical energy storage devices (right). >
Professor Kang noted that the hybrid sodium-ion energy storage device, capable of rapid charging and achieving an energy density of 247 Wh/kg and a power density of 34,748 W/kg, represents a breakthrough in overcoming the current limitations of energy storage systems. He anticipates broader applications across various electronic devices, including electric vehicles.
This research, co-authored by KAIST doctoral candidates Jong Hui Choi and Dong Won Kim, was published in the international journal Energy Storage Materials on March 29 with the title "Low-crystallinity conductive multivalence iron sulfide-embedded S-doped anode and high-surface-area O-doped cathode of 3D porous N-rich graphitic carbon frameworks for high-performance sodium-ion hybrid energy storages."
The study was conducted with support from the Ministry of Science and ICT and the National Research Foundation of Korea through the Nanomaterial Technology Development Project.
2024.04.18 View 12454