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Centrifugal Multispun Nanofibers Put a New Spin on COVID-19 Masks
KAIST researchers have developed a novel nanofiber production technique called ‘centrifugal multispinning’ that will open the door for the safe and cost-effective mass production of high-performance polymer nanofibers. This new technique, which has shown up to a 300 times higher nanofiber production rate per hour than that of the conventional electrospinning method, has many potential applications including the development of face mask filters for coronavirus protection. Nanofibers make good face mask filters because their mechanical interactions with aerosol particles give them a greater ability to capture more than 90% of harmful particles such as fine dust and virus-containing droplets. The impact of the COVID-19 pandemic has further accelerated the growing demand in recent years for a better kind of face mask. A polymer nanofiber-based mask filter that can more effectively block harmful particles has also been in higher demand as the pandemic continues. ‘Electrospinning’ has been a common process used to prepare fine and uniform polymer nanofibers, but in terms of safety, cost-effectiveness, and mass production, it has several drawbacks. The electrospinning method requires a high-voltage electric field and electrically conductive target, and this hinders the safe and cost-effective mass production of polymer nanofibers. In response to this shortcoming, ‘centrifugal spinning’ that utilizes centrifugal force instead of high voltage to produce polymer nanofibers has been suggested as a safer and more cost-effective alternative to the electrospinning. Easy scalability is another advantage, as this technology only requires a rotating spinneret and a collector. However, since the existing centrifugal force-based spinning technology employs only a single rotating spinneret, productivity is limited and not much higher than that of some advanced electrospinning technologies such as ‘multi-nozzle electrospinning’ and ‘nozzleless electrospinning.’ This problem persists even when the size of the spinneret is increased. Inspired by these limitations, a research team led by Professor Do Hyun Kim from the Department of Chemical and Biomolecular Engineering at KAIST developed a centrifugal multispinning spinneret with mass-producibility, by sectioning a rotating spinneret into three sub-disks. This study was published as a front cover article of ACS Macro Letters, Volume 10, Issue 3 in March 2021. Using this new centrifugal multispinning spinneret with three sub-disks, the lead author of the paper PhD candidate Byeong Eun Kwak and his fellow researchers Hyo Jeong Yoo and Eungjun Lee demonstrated the gram-scale production of various polymer nanofibers with a maximum production rate of up to 25 grams per hour, which is approximately 300 times higher than that of the conventional electrospinning system. The production rate of up to 25 grams of polymer nanofibers per hour corresponds to the production rate of about 30 face mask filters per day in a lab-scale manufacturing system. By integrating the mass-produced polymer nanofibers into the form of a mask filter, the researchers were able to fabricate face masks that have comparable filtration performance with the KF80 and KF94 face masks that are currently available in the Korean market. The KF80 and KF94 masks have been approved by the Ministry of Food and Drug Safety of Korea to filter out at least 80% and 94% of harmful particles respectively. “When our system is scaled up from the lab scale to an industrial scale, the large-scale production of centrifugal multispun polymer nanofibers will be made possible, and the cost of polymer nanofiber-based face mask filters will also be lowered dramatically,” Kwak explained. This work was supported by the KAIST-funded Global Singularity Research Program for 2020. Publication: Byeong Eun Kwak, Hyo Jeong Yoo, Eungjun Lee, and Do Hyun Kim. (2021) Large-Scale Centrifugal Multispinning Production of Polymer Micro- and Nanofibers for Mask Filter Application with a Potential of Cospinning Mixed Multicomponent Fibers. ACS Macro Letters, Volume No. 10, Issue No. 3, pp. 382-388. Available online at https://doi.org/10.1021/acsmacrolett.0c00829 Profile: Do Hyun Kim, Sc.D. Professor dohyun.kim@kaist.edu http://procal.kaist.ac.kr/ Process Analysis Laboratory Department of Chemical and Biomolecular Engineering https:/kaist.ac.kr/en/ Korea Advanced Institute of Science and Technology (KAIST)Daejeon 34141, Korea (END)
2021.04.12
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Microbial Production of a Natural Red Colorant Carminic Acid
Metabolic engineering and computer-simulated enzyme engineering led to the production of carminic acid, a natural red colorant, from bacteria for the first time A research group at KAIST has engineered a bacterium capable of producing a natural red colorant, carminic acid, which is widely used for food and cosmetics. The research team reported the complete biosynthesis of carminic acid from glucose in engineered Escherichia coli. The strategies will be useful for the design and construction of biosynthetic pathways involving unknown enzymes and consequently the production of diverse industrially important natural products for the food, pharmaceutical, and cosmetic industries. Carminic acid is a natural red colorant widely being used for products such as strawberry milk and lipstick. However, carminic acid has been produced by farming cochineals, a scale insect which only grows in the region around Peru and Canary Islands, followed by complicated multi-step purification processes. Moreover, carminic acid often contains protein contaminants that cause allergies so many people are unwilling to consume products made of insect-driven colorants. On that account, manufacturers around the world are using alternative red colorants despite the fact that carminic acid is one of the most stable natural red colorants. These challenges inspired the metabolic engineering research group at KAIST to address this issue. Its members include postdoctoral researchers Dongsoo Yang and Woo Dae Jang, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering. This study entitled “Production of carminic acid by metabolically engineered Escherichia coli” was published online in the Journal of the American Chemical Society (JACS) on April 2. This research reports for the first time the development of a bacterial strain capable of producing carminic acid from glucose via metabolic engineering and computer simulation-assisted enzyme engineering. The research group optimized the type II polyketide synthase machinery to efficiently produce the precursor of carminic acid, flavokermesic acid. Since the enzymes responsible for the remaining two reactions were neither discovered nor functional, biochemical reaction analysis was performed to identify enzymes that can convert flavokermesic acid into carminic acid. Then, homology modeling and docking simulations were performed to enhance the activities of the two identified enzymes. The team could confirm that the final engineered strain could produce carminic acid directly from glucose. The C-glucosyltransferase developed in this study was found to be generally applicable for other natural products as showcased by the successful production of an additional product, aloesin, which is found in aloe leaves. “The most important part of this research is that unknown enzymes for the production of target natural products were identified and improved by biochemical reaction analyses and computer simulation-assisted enzyme engineering,” says Dr. Dongsoo Yang. He explained the development of a generally applicable C-glucosyltransferase is also useful since C-glucosylation is a relatively unexplored reaction in bacteria including Escherichia coli. Using the C-glucosyltransferase developed in this study, both carminic acid and aloesin were successfully produced from glucose. “A sustainable and insect-free method of producing carminic acid was achieved for the first time in this study. Unknown or inefficient enzymes have always been a major problem in natural product biosynthesis, and here we suggest one effective solution for solving this problem. As maintaining good health in the aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” said Distinguished Professor Sang Yup Lee. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries of the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF) of Korea and the KAIST Cross-Generation Collaborative Lab project; Sang Yup Lee and Dongsoo Yang were also supported by Novo Nordisk Foundation in Denmark. Publication: Dongsoo Yang, Woo Dae Jang, and Sang Yup Lee. Production of carminic acid by metabolically engineered Escherichia coli. at the Journal of the American Chemical Society. https://doi.org.10.1021/jacs.0c12406 Profile: Sang Yup Lee, PhD Distinguished Professor leesy@kaist.ac.kr http://mbel.kaist.ac.kr Metabolic &Biomolecular Engineering National Research Laboratory Department of Chemical and Biomolecular Engineering KAIST
2021.04.06
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Streamlining the Process of Materials Discovery
The materials platform M3I3 reduces the time for materials discovery by reverse engineering future materials using multiscale/multimodal imaging and machine learning of the processing-structure-properties relationship Developing new materials and novel processes has continued to change the world. The M3I3 Initiative at KAIST has led to new insights into advancing materials development by implementing breakthroughs in materials imaging that have created a paradigm shift in the discovery of materials. The Initiative features the multiscale modeling and imaging of structure and property relationships and materials hierarchies combined with the latest material-processing data. The research team led by Professor Seungbum Hong analyzed the materials research projects reported by leading global institutes and research groups, and derived a quantitative model using machine learning with a scientific interpretation. This process embodies the research goal of the M3I3: Materials and Molecular Modeling, Imaging, Informatics and Integration. The researchers discussed the role of multiscale materials and molecular imaging combined with machine learning and also presented a future outlook for developments and the major challenges of M3I3. By building this model, the research team envisions creating desired sets of properties for materials and obtaining the optimum processing recipes to synthesize them. “The development of various microscopy and diffraction tools with the ability to map the structure, property, and performance of materials at multiscale levels and in real time enabled us to think that materials imaging could radically accelerate materials discovery and development,” says Professor Hong. “We plan to build an M3I3 repository of searchable structural and property maps using FAIR (Findable, Accessible, Interoperable, and Reusable) principles to standardize best practices as well as streamline the training of early career researchers.” One of the examples that shows the power of structure-property imaging at the nanoscale is the development of future materials for emerging nonvolatile memory devices. Specifically, the research team focused on microscopy using photons, electrons, and physical probes on the multiscale structural hierarchy, as well as structure-property relationships to enhance the performance of memory devices. “M3I3 is an algorithm for performing the reverse engineering of future materials. Reverse engineering starts by analyzing the structure and composition of cutting-edge materials or products. Once the research team determines the performance of our targeted future materials, we need to know the candidate structures and compositions for producing the future materials.” The research team has built a data-driven experimental design based on traditional NCM (nickel, cobalt, and manganese) cathode materials. With this, the research team expanded their future direction for achieving even higher discharge capacity, which can be realized via Li-rich cathodes. However, one of the major challenges was the limitation of available data that describes the Li-rich cathode properties. To mitigate this problem, the researchers proposed two solutions: First, they should build a machine-learning-guided data generator for data augmentation. Second, they would use a machine-learning method based on ‘transfer learning.’ Since the NCM cathode database shares a common feature with a Li-rich cathode, one could consider repurposing the NCM trained model for assisting the Li-rich prediction. With the pretrained model and transfer learning, the team expects to achieve outstanding predictions for Li-rich cathodes even with the small data set. With advances in experimental imaging and the availability of well-resolved information and big data, along with significant advances in high-performance computing and a worldwide thrust toward a general, collaborative, integrative, and on-demand research platform, there is a clear confluence in the required capabilities of advancing the M3I3 Initiative. Professor Hong said, “Once we succeed in using the inverse “property−structure−processing” solver to develop cathode, anode, electrolyte, and membrane materials for high energy density Li-ion batteries, we will expand our scope of materials to battery/fuel cells, aerospace, automobiles, food, medicine, and cosmetic materials.” The review was published in ACS Nano in March. This study was conducted through collaborations with Dr. Chi Hao Liow, Professor Jong Min Yuk, Professor Hye Ryung Byon, Professor Yongsoo Yang, Professor EunAe Cho, Professor Pyuck-Pa Choi, and Professor Hyuck Mo Lee at KAIST, Professor Joshua C. Agar at Lehigh University, Dr. Sergei V. Kalinin at Oak Ridge National Laboratory, Professor Peter W. Voorhees at Northwestern University, and Professor Peter Littlewood at the University of Chicago (Article title: Reducing Time to Discovery: Materials and Molecular Modeling, Imaging, Informatics, and Integration).This work was supported by the KAIST Global Singularity Research Program for 2019 and 2020. Publication: “Reducing Time to Discovery: Materials and Molecular Modeling, Imaging, Informatics and Integration,” S. Hong, C. H. Liow, J. M. Yuk, H. R. Byon, Y. Yang, E. Cho, J. Yeom, G. Park, H. Kang, S. Kim, Y. Shim, M. Na, C. Jeong, G. Hwang, H. Kim, H. Kim, S. Eom, S. Cho, H. Jun, Y. Lee, A. Baucour, K. Bang, M. Kim, S. Yun, J. Ryu, Y. Han, A. Jetybayeva, P.-P. Choi, J. C. Agar, S. V. Kalinin, P. W. Voorhees, P. Littlewood, and H. M. Lee, ACS Nano 15, 3, 3971–3995 (2021) https://doi.org/10.1021/acsnano.1c00211 Profile: Seungbum Hong, PhD Associate Professor seungbum@kaist.ac.kr http://mii.kaist.ac.kr Department of Materials Science and Engineering KAIST (END)
2021.04.05
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Plasma Jets Stabilize Water to Splash Less
< High-speed shadowgraph movie of water surface deformations induced by plasma impingement. > A study by KAIST researchers revealed that an ionized gas jet blowing onto water, also known as a ‘plasma jet’, produces a more stable interaction with the water’s surface compared to a neutral gas jet. This finding reported in the April 1 issue of Nature will help improve the scientific understanding of plasma-liquid interactions and their practical applications in a wide range of industrial fields in which fluid control technology is used, including biomedical engineering, chemical production, and agriculture and food engineering. Gas jets can create dimple-like depressions in liquid surfaces, and this phenomenon is familiar to anyone who has seen the cavity produced by blowing air through a straw directly above a cup of juice. As the speed of the gas jet increases, the cavity becomes unstable and starts bubbling and splashing. “Understanding the physical properties of interactions between gases and liquids is crucial for many natural and industrial processes, such as the wind blowing over the surface of the ocean, or steelmaking methods that involve blowing oxygen over the top of molten iron,” explained Professor Wonho Choe, a physicist from KAIST and the corresponding author of the study. However, despite its scientific and practical importance, little is known about how gas-blown liquid cavities become deformed and destabilized. In this study, a group of KAIST physicists led by Professor Choe and the team’s collaborators from Chonbuk National University in Korea and the Jožef Stefan Institute in Slovenia investigated what happens when an ionized gas jet, also known as a ‘plasma jet’, is blown over water. A plasma jet is created by applying high voltage to a nozzle as gas flows through it, which causes the gas to be weakly ionized and acquire freely-moving charged particles. The research team used an optical technique combined with high-speed imaging to observe the profiles of the water surface cavities created by both neutral helium gas jets and weakly ionized helium gas jets. They also developed a computational model to mathematically explain the mechanisms behind their experimental discovery. The researchers demonstrated for the first time that an ionized gas jet has a stabilizing effect on the water’s surface. They found that certain forces exerted by the plasma jet make the water surface cavity more stable, meaning there is less bubbling and splashing compared to the cavity created by a neutral gas jet. Specifically, the study showed that the plasma jet consists of pulsed waves of gas ionization propagating along the water’s surface so-called ‘plasma bullets’ that exert more force than a neutral gas jet, making the cavity deeper without becoming destabilized. “This is the first time that this phenomenon has been reported, and our group considers this as a critical step forward in our understanding of how plasma jets interact with liquid surfaces. We next plan to expand this finding through more case studies that involve diverse plasma and liquid characteristics,” said Professor Choe. This work was supported by KAIST as part of the High-Risk and High-Return Project, the National Research Foundation of Korea (NRF), and the Slovenian Research Agency (ARRS). Image Credit: Professor Wonho Choe, KAIST Usage Restrictions: News organizations may use or redistribute these materials, with proper attribution, as part of news coverage of this paper only. Publication: Park, S., et al. (2021) Stabilization of liquid instabilities with ionized gas jets. Nature, Vol. No. 592, Issue No. 7852, pp. 49-53. Available online at https://doi.org/10.1038/s41586-021-03359-9 Profile: Wonho Choe, Ph.D. Professor wchoe@kaist.ac.kr https://gdpl.kaist.ac.kr/ Gas Discharge Physics Laboratory (GDPL) Department of Nuclear and Quantum Engineering Department of Physics Impurity and Edge Plasma Research Center (IERC) http://kaist.ac.kr/en/ Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea (END)
2021.04.01
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Acoustic Graphene Plasmons Study Paves Way for Optoelectronic Applications
- The first images of mid-infrared optical waves compressed 1,000 times captured using a highly sensitive scattering-type scanning near-field optical microscope. - KAIST researchers and their collaborators at home and abroad have successfully demonstrated a new methodology for direct near-field optical imaging of acoustic graphene plasmon fields. This strategy will provide a breakthrough for the practical applications of acoustic graphene plasmon platforms in next-generation, high-performance, graphene-based optoelectronic devices with enhanced light-matter interactions and lower propagation loss. It was recently demonstrated that ‘graphene plasmons’ – collective oscillations of free electrons in graphene coupled to electromagnetic waves of light – can be used to trap and compress optical waves inside a very thin dielectric layer separating graphene from a metallic sheet. In such a configuration, graphene’s conduction electrons are “reflected” in the metal, so when the light waves “push” the electrons in graphene, their image charges in metal also start to oscillate. This new type of collective electronic oscillation mode is called ‘acoustic graphene plasmon (AGP)’. The existence of AGP could previously be observed only via indirect methods such as far-field infrared spectroscopy and photocurrent mapping. This indirect observation was the price that researchers had to pay for the strong compression of optical waves inside nanometer-thin structures. It was believed that the intensity of electromagnetic fields outside the device was insufficient for direct near-field optical imaging of AGP. Challenged by these limitations, three research groups combined their efforts to bring together a unique experimental technique using advanced nanofabrication methods. Their findings were published in Nature Communications on February 19. A KAIST research team led by Professor Min Seok Jang from the School of Electrical Engineering used a highly sensitive scattering-type scanning near-field optical microscope (s-SNOM) to directly measure the optical fields of the AGP waves propagating in a nanometer-thin waveguide, visualizing thousand-fold compression of mid-infrared light for the first time. Professor Jang and a post-doc researcher in his group, Sergey G. Menabde, successfully obtained direct images of AGP waves by taking advantage of their rapidly decaying yet always present electric field above graphene. They showed that AGPs are detectable even when most of their energy is flowing inside the dielectric below the graphene. This became possible due to the ultra-smooth surfaces inside the nano-waveguides where plasmonic waves can propagate at longer distances. The AGP mode probed by the researchers was up to 2.3 times more confined and exhibited a 1.4 times higher figure of merit in terms of the normalized propagation length compared to the graphene surface plasmon under similar conditions. These ultra-smooth nanostructures of the waveguides used in the experiment were created using a template-stripping method by Professor Sang-Hyun Oh and a post-doc researcher, In-Ho Lee, from the Department of Electrical and Computer Engineering at the University of Minnesota. Professor Young Hee Lee and his researchers at the Center for Integrated Nanostructure Physics (CINAP) of the Institute of Basic Science (IBS) at Sungkyunkwan University synthesized the graphene with a monocrystalline structure, and this high-quality, large-area graphene enabled low-loss plasmonic propagation. The chemical and physical properties of many important organic molecules can be detected and evaluated by their absorption signatures in the mid-infrared spectrum. However, conventional detection methods require a large number of molecules for successful detection, whereas the ultra-compressed AGP fields can provide strong light-matter interactions at the microscopic level, thus significantly improving the detection sensitivity down to a single molecule. Furthermore, the study conducted by Professor Jang and the team demonstrated that the mid-infrared AGPs are inherently less sensitive to losses in graphene due to their fields being mostly confined within the dielectric. The research team’s reported results suggest that AGPs could become a promising platform for electrically tunable graphene-based optoelectronic devices that typically suffer from higher absorption rates in graphene such as metasurfaces, optical switches, photovoltaics, and other optoelectronic applications operating at infrared frequencies. Professor Jang said, “Our research revealed that the ultra-compressed electromagnetic fields of acoustic graphene plasmons can be directly accessed through near-field optical microscopy methods. I hope this realization will motivate other researchers to apply AGPs to various problems where strong light-matter interactions and lower propagation loss are needed.” This research was primarily funded by the Samsung Research Funding & Incubation Center of Samsung Electronics. The National Research Foundation of Korea (NRF), the U.S. National Science Foundation (NSF), Samsung Global Research Outreach (GRO) Program, and Institute for Basic Science of Korea (IBS) also supported the work. Publication: Menabde, S. G., et al. (2021) Real-space imaging of acoustic plasmons in large-area graphene grown by chemical vapor deposition. Nature Communications 12, Article No. 938. Available online at https://doi.org/10.1038/s41467-021-21193-5 Profile: Min Seok Jang, MS, PhD Associate Professorjang.minseok@kaist.ac.krhttp://jlab.kaist.ac.kr/ Min Seok Jang Research GroupSchool of Electrical Engineering http://kaist.ac.kr/en/Korea Advanced Institute of Science and Technology (KAIST)Daejeon, Republic of Korea (END)
2021.03.16
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Rare Mutations May Have Big Impact on Schizophrenia Pathology
- Somatic mutations found only in brain cells disrupt synaptic function. - Schizophrenia is a neurodevelopmental disorder that disrupts brain activity, producing hallucinations, delusions, and other cognitive disturbances. Researchers have long searched for genetic influences in the disease, but genetic mutations have been identified in only a small fraction—fewer than a quarter—of sequenced patients. Now a study shows that “somatic” gene mutations in brain cells could account for some of the disease’s neuropathology. The results of the study, led by Professor Jeong Ho Lee at the Graduate School of Medical Science and Engineering in collaboration with the Stanley Medical Research Institute in the US, appeared in Biological Psychiatry. Traditional genetic mutations, called germline mutations, occur in sperm or egg cells and are passed on to offspring by their parents. Somatic mutations, in contrast, occur in an embryo after fertilization, and they can show up throughout the body or in isolated pockets of tissues, making them much harder to detect from blood or saliva samples, which are typically used for such sequencing studies. Recently, more-advanced genetic sequencing techniques have allowed researchers to detect somatic mutations and studies have shown that even mutations present at very low levels can have functional consequences. A previous study hinted that brain somatic mutations were associated with schizophrenia, but it was not powerful enough to cement an association between brain somatic mutations and schizophrenia. In the current study, the researchers used deep whole-exome sequencing to determine the genetic code of all exomes, the parts of genes that encode proteins. The scientists sequenced postmortem samples from brain, liver, spleen, or heart tissue of 27 people with schizophrenia and 31 control participants allowing them to compare the sequences in the two tissues. Using a powerful analytic technique, the team identified an average of 4.9 somatic single-nucleotide variants, or mutations, in brain samples from people with schizophrenia, and 5.6 somatic single-nucleotide variants in brain samples from control subjects. Although there were no significant quantitative differences in somatic single-nucleotide variants between schizophrenia and control tissue samples, the researchers found that the mutations in schizophrenia patients were found in genes already associated with schizophrenia. Of the germline mutations that had previously been associated with schizophrenia, the genes affected encode proteins associated with synaptic neural communication, particularly in a brain region called the dorsolateral prefrontal cortex. In the new analysis, the researchers determined which proteins might be affected by the newly identified somatic mutations. Remarkably, a protein called GRIN2B emerged as highly affected and two patients with schizophrenia carried somatic mutations on the GRIN2B gene itself. GRIN2B is a protein component of NMDA-type glutamate receptors, which are critical for neural signaling. Faulty glutamate receptors have long been suspected of contributing to schizophrenia pathology; GRIN2B ranks among the most-studied genes in schizophrenia. The somatic mutations identified in the study had a variant allele frequency of only ~1%, indicating that the mutations were rare among brain cells as a whole. Nevertheless, they have the potential to create widespread cortical dysfunction. Professor Lee said, “Besides the comprehensive genetic analysis of brain-only mutations in postmortem tissues from schizophrenia patients, this study experimentally showed the biological consequence of identified somatic mutations, which led to neuronal abnormalities associated with schizophrenia. Thus, this study suggests that brain somatic mutations can be a hidden major contributor to schizophrenia and provides new insights into the molecular genetic architecture of schizophrenia. John Krystal, MD, editor of Biological Psychiatry, said of the work, "The genetics of schizophrenia has received intensive study for several decades. Now a new possibility emerges, that in some cases, mutations in the DNA of brain cells contributes to the biology of schizophrenia. Remarkably this new biology points to an old schizophrenia story: NMDA glutamate receptor dysfunction. Perhaps the path through which somatic mutations contribute to schizophrenia converges with other sources of abnormalities in glutamate signaling in this disorder." Professor Lee and the team next want to assess the functional consequences of the somatic mutations. Because of the location of the GRIN2B mutations found in schizophrenia patients, the researchers hypothesized that they might interfere with the receptors’ localization on neurons. Experiments on the cortical neurons of mice showed that the mutations indeed disrupted the receptors’ usual localization to dendrites, the “listening” ends of neurons, which in turn prevented the formation of normal synapses in the neurons. This finding suggests that the somatic mutations could disrupt neural communication, contributing to schizophrenia pathology. - Profile: Professor Jeong Ho Lee Translational Neurogenetics Laboratory ( https://tnl.kaist.ac.kr/) The Graduate School of Medical Science and Engineering KAIST (END)
2021.03.11
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ACS Nano Special Edition Highlights Innovations at KAIST
- The collective intelligence and technological innovation of KAIST was highlighted with case studies including the Post-COVID-19 New Deal R&D Initiative Project. - KAIST’s innovative academic achievements and R&D efforts for addressing the world’s greatest challenges such as the COVID-19 pandemic were featured in ACS Nano as part of its special virtual issue commemorating the 50th anniversary of KAIST. The issue consisted of 14 review articles contributed by KAIST faculty from five departments, including two from Professor Il-Doo Kim from the Department of Materials Science and Engineering, who serves as an associate editor of the ACS Nano. ACS Nano, the leading international journal in nanoscience and nanotechnology, published a special virtual issue last month, titled ‘Celebrating 50 Years of KAIST: Collective Intelligence and Innovation for Confronting Contemporary Issues.’ This special virtual issue introduced KAIST’s vision of becoming a ‘global value-creative leading university’ and its progress toward this vision over the last 50 years. The issue explained how KAIST has served as the main hub for advanced scientific research and technological innovation in South Korea since its establishment in 1971, and how its faculty and over 69,000 graduates played a key role in propelling the nation’s rapid industrialization and economic development. The issue also emphasized the need for KAIST to enhance global cooperation and the exchange of ideas in the years to come, especially during the post-COVID era intertwined with the Fourth Industrial Revolution (4IR). In this regard, the issue cited the first ‘KAIST Emerging Materials e-Symposium (EMS)’, which was held online for five days in September of last year with a global audience of over 10,000 participating live via Zoom and YouTube, as a successful example of what academic collaboration could look like in the post-COVID and 4IR eras. In addition, the “Science & Technology New Deal Project for COVID-19 Response,” a project conducted by KAIST with support from the Ministry of Science and ICT (MSIT) of South Korea, was also introduced as another excellent case of KAIST’s collective intelligence and technological innovation. The issue highlighted some key achievements from this project for overcoming the pandemic-driven crisis, such as: reusable anti-virus filters, negative-pressure ambulances for integrated patient transport and hospitalization, and movable and expandable negative-pressure ward modules. “We hold our expectations high for the outstanding achievements and progress KAIST will have made by its centennial,” said Professor Kim on the background of curating the 14 review articles contributed by KAIST faculty from the fields of Materials Science and Engineering (MSE), Chemical and Biomolecular Engineering (CBE), Nuclear and Quantum Engineering (NQE), Electrical Engineering (EE), and Chemistry (Chem). Review articles discussing emerging materials and their properties covered photonic carbon dots (Professor Chan Beum Park, MSE), single-atom and ensemble catalysts (Professor Hyunjoo Lee, CBE), and metal/metal oxide electrocatalysts (Professor Sung-Yoon Chung, MSE). Review articles discussing materials processing covered 2D layered materials synthesis based on interlayer engineering (Professor Kibum Kang, MSE), eco-friendly methods for solar cell production (Professor Bumjoon J. Kim, CBE), an ex-solution process for the synthesis of highly stable catalysts (Professor WooChul Jung, MSE), and 3D light-patterning synthesis of ordered nanostructures (Professor Seokwoo Jeon, MSE, and Professor Dongchan Jang, NQE). Review articles discussing advanced analysis techniques covered operando materials analyses (Professor Jeong Yeong Park, Chem), graphene liquid cell transmission electron microscopy (Professor Jong Min Yuk, MSE), and multiscale modeling and visualization of materials systems (Professor Seungbum Hong, MSE). Review articles discussing practical state-of-the-art devices covered chemiresistive hydrogen sensors (Professor Il-Doo Kim, MSE), patient-friendly diagnostics and implantable treatment devices (Professor Steve Park, MSE), triboelectric nanogenerators (Professor Yang-Kyu Choi, EE), and next-generation lithium-air batteries (Professor Hye Ryung Byon, Chem, and Professor Il-Doo Kim, MSE). In addition to Professor Il-Doo Kim, post-doctoral researcher Dr. Jaewan Ahn from the KAIST Applied Science Research Institute, Dean of the College of Engineering at KAIST Professor Choongsik Bae, and ACS Nano Editor-in-Chief Professor Paul S. Weiss from the University of California, Los Angeles also contributed to the publication of this ACS Nano special virtual issue. The issue can be viewed and downloaded from the ACS Nano website at https://doi.org/10.1021/acsnano.1c01101. Image credit: KAIST Image usage restrictions: News organizations may use or redistribute this image,with proper attribution, as part of news coverage of this paper only. Publication: Ahn, J., et al. (2021) Celebrating 50 Years of KAIST: Collective Intelligence and Innovation for Confronting Contemporary Issues. ACS Nano 15(3): 1895-1907. Available online at https://doi.org/10.1021/acsnano.1c01101 Profile: Il-Doo Kim, Ph.D Chair Professor idkim@kaist.ac.kr http://advnano.kaist.ac.kr Advanced Nanomaterials and Energy Lab. Department of Materials Science and Engineering Membrane Innovation Center for Anti-Virus and Air-Quality Control https://kaist.ac.kr/ Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea (END)
2021.03.05
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Deep-Learning and 3D Holographic Microscopy Beats Scientists at Analyzing Cancer Immunotherapy
Live tracking and analyzing of the dynamics of chimeric antigen receptor (CAR) T-cells targeting cancer cells can open new avenues for the development of cancer immunotherapy. However, imaging via conventional microscopy approaches can result in cellular damage, and assessments of cell-to-cell interactions are extremely difficult and labor-intensive. When researchers applied deep learning and 3D holographic microscopy to the task, however, they not only avoided these difficultues but found that AI was better at it than humans were. Artificial intelligence (AI) is helping researchers decipher images from a new holographic microscopy technique needed to investigate a key process in cancer immunotherapy “live” as it takes place. The AI transformed work that, if performed manually by scientists, would otherwise be incredibly labor-intensive and time-consuming into one that is not only effortless but done better than they could have done it themselves. The research, conducted by the team of Professor YongKeun Park from the Department of Physics, appeared in the journal eLife last December. A critical stage in the development of the human immune system’s ability to respond not just generally to any invader (such as pathogens or cancer cells) but specifically to that particular type of invader and remember it should it attempt to invade again is the formation of a junction between an immune cell called a T-cell and a cell that presents the antigen, or part of the invader that is causing the problem, to it. This process is like when a picture of a suspect is sent to a police car so that the officers can recognize the criminal they are trying to track down. The junction between the two cells, called the immunological synapse, or IS, is the key process in teaching the immune system how to recognize a specific type of invader. Since the formation of the IS junction is such a critical step for the initiation of an antigen-specific immune response, various techniques allowing researchers to observe the process as it happens have been used to study its dynamics. Most of these live imaging techniques rely on fluorescence microscopy, where genetic tweaking causes part of a protein from a cell to fluoresce, in turn allowing the subject to be tracked via fluorescence rather than via the reflected light used in many conventional microscopy techniques. However, fluorescence-based imaging can suffer from effects such as photo-bleaching and photo-toxicity, preventing the assessment of dynamic changes in the IS junction process over the long term. Fluorescence-based imaging still involves illumination, whereupon the fluorophores (chemical compounds that cause the fluorescence) emit light of a different color. Photo-bleaching or photo-toxicity occur when the subject is exposed to too much illumination, resulting in chemical alteration or cellular damage. One recent option that does away with fluorescent labelling and thereby avoids such problems is 3D holographic microscopy or holotomography (HT). In this technique, the refractive index (the way that light changes direction when encountering a substance with a different density—why a straw looks like it bends in a glass of water) is recorded in 3D as a hologram. Until now, HT has been used to study single cells, but never cell-cell interactions involved in immune responses. One of the main reasons is the difficulty of “segmentation,” or distinguishing the different parts of a cell and thus distinguishing between the interacting cells; in other words, deciphering which part belongs to which cell. Manual segmentation, or marking out the different parts manually, is one option, but it is difficult and time-consuming, especially in three dimensions. To overcome this problem, automatic segmentation has been developed in which simple computer algorithms perform the identification. “But these basic algorithms often make mistakes,” explained Professor YongKeun Park, “particularly with respect to adjoining segmentation, which of course is exactly what is occurring here in the immune response we’re most interested in.” So, the researchers applied a deep learning framework to the HT segmentation problem. Deep learning is a type of machine learning in which artificial neural networks based on the human brain recognize patterns in a way that is similar to how humans do this. Regular machine learning requires data as an input that has already been labelled. The AI “learns” by understanding the labeled data and then recognizes the concept that has been labelled when it is fed novel data. For example, AI trained on a thousand images of cats labelled “cat” should be able to recognize a cat the next time it encounters an image with a cat in it. Deep learning involves multiple layers of artificial neural networks attacking much larger, but unlabeled datasets, in which the AI develops its own ‘labels’ for concepts it encounters. In essence, the deep learning framework that KAIST researchers developed, called DeepIS, came up with its own concepts by which it distinguishes the different parts of the IS junction process. To validate this method, the research team applied it to the dynamics of a particular IS junction formed between chimeric antigen receptor (CAR) T-cells and target cancer cells. They then compared the results to what they would normally have done: the laborious process of performing the segmentation manually. They found not only that DeepIS was able to define areas within the IS with high accuracy, but that the technique was even able to capture information about the total distribution of proteins within the IS that may not have been easily measured using conventional techniques. “In addition to allowing us to avoid the drudgery of manual segmentation and the problems of photo-bleaching and photo-toxicity, we found that the AI actually did a better job,” Professor Park added. The next step will be to combine the technique with methods of measuring how much physical force is applied by different parts of the IS junction, such as holographic optical tweezers or traction force microscopy. -Profile Professor YongKeun Park Department of Physics Biomedical Optics Laboratory http://bmol.kaist.ac.kr KAIST
2021.02.24
View 10435
Attachable Skin Monitors that Wick the Sweat Away
- A silicone membrane for wearable devices is more comfortable and breathable thanks to better-sized pores made with the help of citric acid crystals. - A new preparation technique fabricates thin, silicone-based patches that rapidly wick water away from the skin. The technique could reduce the redness and itching caused by wearable biosensors that trap sweat beneath them. The technique was developed by bioengineer and professor Young-Ho Cho and his colleagues at KAIST and reported in the journal Scientific Reports last month. “Wearable bioelectronics are becoming more attractive for the day-to-day monitoring of biological compounds found in sweat, like hormones or glucose, as well as body temperature, heart rate, and energy expenditure,” Professor Cho explained. “But currently available materials can cause skin irritation, so scientists are looking for ways to improve them,” he added. Attachable biosensors often use a silicone-based compound called polydimethylsiloxane (PDMS), as it has a relatively high water vapour transmission rate compared to other materials. Still, this rate is only two-thirds that of skin’s water evaporation rate, meaning sweat still gets trapped underneath it. Current fabrication approaches mix PDMS with beads or solutes, such as sugars or salts, and then remove them to leave pores in their place. Another technique uses gas to form pores in the material. Each technique has its disadvantages, from being expensive and complex to leaving pores of different sizes. A team of researchers led by Professor Cho from the KAIST Department of Bio and Brain Engineering was able to form small, uniform pores by crystallizing citric acid in PDMS and then removing the crystals using ethanol. The approach is significantly cheaper than using beads, and leads to 93.2% smaller and 425% more uniformly-sized pores compared to using sugar. Importantly, the membrane transmits water vapour 2.2 times faster than human skin. The team tested their membrane on human skin for seven days and found that it caused only minor redness and no itching, whereas a non-porous PDMS membrane did. Professor Cho said, “Our method could be used to fabricate porous PDMS membranes for skin-attachable devices used for daily monitoring of physiological signals.” “We next plan to modify our membrane so it can be more readily attached to and removed from skin,” he added. This work was supported by the Ministry of Trade, Industry and Energy (MOTIE) of Korea under the Alchemist Project. Image description: Smaller, more uniformly-sized pores are made in the PDMS membrane by mixing PDMS, toluene, citric acid, and ethanol. Toluene dilutes PDMS so it can easily mix with the other two constituents. Toluene and ethanol are then evaporated, which causes the citric acid to crystallize within the PDMS material. The mixture is placed in a mould where it solidifies into a thin film. The crystals are then removed using ethanol, leaving pores in their place. Image credit: Professor Young-Ho Cho, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Yoon, S, et al. (2021) Wearable porous PDMS layer of high moisture permeability for skin trouble reduction. Scientific Reports 11, Article No. 938. Available online at https://doi.org/10.1038/s41598-020-78580-z Profile: Young-Ho Cho, Ph.D Professor mems@kaist.ac.kr https://mems.kaist.ac.kr NanoSentuating Systems Laboratory Department of Bio and Brain Engineering https://kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea (END)
2021.02.22
View 11018
Highly Deformable Piezoelectric Nanotruss for Tactile Electronics
With the importance of non-contact environments growing due to COVID-19, tactile electronic devices using haptic technology are gaining traction as new mediums of communication. Haptic technology is being applied in a wide array of fields such as robotics or interactive displays. haptic gloves are being used for augmented information communication technology. Efficient piezoelectric materials that can convert various mechanical stimuli into electrical signals and vice versa are a prerequisite for advancing high-performing haptic technology. A research team led by Professor Seungbum Hong confirmed the potential of tactile devices by developing ceramic piezoelectric materials that are three times more deformable. For the fabrication of highly deformable nanomaterials, the research team built a zinc oxide hollow nanostructure using proximity field nanopatterning and atomic layered deposition. The piezoelectric coefficient was measured to be approximately 9.2 pm/V and the nanopillar compression test showed an elastic strain limit of approximately 10%, which is more than three times greater than that of the bulk zinc oxide one. Piezoelectric ceramics have a high piezoelectric coefficient with a low elastic strain limit, whereas the opposite is true for piezoelectric polymers. Therefore, it has been very challenging to obtain good performance in both high piezoelectric coefficients as well as high elastic strain limits. To break the elastic limit of piezoelectric ceramics, the research team introduced a 3D truss-like hollow nanostructure with nanometer-scale thin walls. According to the Griffith criterion, the fracture strength of a material is inversely proportional to the square root of the preexisting flaw size. However, a large flaw is less likely to occur in a small structure, which, in turn, enhances the strength of the material. Therefore, implementing the form of a 3D truss-like hollow nanostructure with nanometer-scale thin walls can extend the elastic limit of the material. Furthermore, a monolithic 3D structure can withstand large strains in all directions while simultaneously preventing the loss from the bottleneck. Previously, the fracture property of piezoelectric ceramic materials was difficult to control, owing to the large variance in crack sizes. However, the research team structurally limited the crack sizes to manage the fracture properties. Professor Hong’s results demonstrate the potential for the development of highly deformable ceramic piezoelectric materials by improving the elastic limit using a 3D hollow nanostructure. Since zinc oxide has a relatively low piezoelectric coefficient compared to other piezoelectric ceramic materials, applying the proposed structure to such components promised better results in terms of the piezoelectric activity. “With the advent of the non-contact era, the importance of emotional communication is increasing. Through the development of novel tactile interaction technologies, in addition to the current visual and auditory communication, mankind will enter a new era where they can communicate with anyone using all five senses regardless of location as if they are with them in person,” Professor Hong said. “While additional research must be conducted to realize the application of the proposed designs for haptic enhancement devices, this study holds high value in that it resolves one of the most challenging issues in the use of piezoelectric ceramics, specifically opening new possibilities for their application by overcoming their mechanical constraints. The research was reported in Nano Energy and supported by the Ministry of Science and ICT, the Korea Research Foundation, and the KAIST Global Singularity Research Project. -Profile: Professor Seungbum Hong seungbum@kaist.ac.kr http://mii.kaist.ac.kr/ Department of Materials Science and Engineering KAIST
2021.02.02
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Wirelessly Rechargeable Soft Brain Implant Controls Brain Cells
Researchers have invented a smartphone-controlled soft brain implant that can be recharged wirelessly from outside the body. It enables long-term neural circuit manipulation without the need for periodic disruptive surgeries to replace the battery of the implant. Scientists believe this technology can help uncover and treat psychiatric disorders and neurodegenerative diseases such as addiction, depression, and Parkinson’s. A group of KAIST researchers and collaborators have engineered a tiny brain implant that can be wirelessly recharged from outside the body to control brain circuits for long periods of time without battery replacement. The device is constructed of ultra-soft and bio-compliant polymers to help provide long-term compatibility with tissue. Geared with micrometer-sized LEDs (equivalent to the size of a grain of salt) mounted on ultrathin probes (the thickness of a human hair), it can wirelessly manipulate target neurons in the deep brain using light. This study, led by Professor Jae-Woong Jeong, is a step forward from the wireless head-mounted implant neural device he developed in 2019. That previous version could indefinitely deliver multiple drugs and light stimulation treatment wirelessly by using a smartphone. For more, Manipulating Brain Cells by Smartphone. For the new upgraded version, the research team came up with a fully implantable, soft optoelectronic system that can be remotely and selectively controlled by a smartphone. This research was published on January 22, 2021 in Nature Communications. The new wireless charging technology addresses the limitations of current brain implants. Wireless implantable device technologies have recently become popular as alternatives to conventional tethered implants, because they help minimize stress and inflammation in freely-moving animals during brain studies, which in turn enhance the lifetime of the devices. However, such devices require either intermittent surgeries to replace discharged batteries, or special and bulky wireless power setups, which limit experimental options as well as the scalability of animal experiments. “This powerful device eliminates the need for additional painful surgeries to replace an exhausted battery in the implant, allowing seamless chronic neuromodulation,” said Professor Jeong. “We believe that the same basic technology can be applied to various types of implants, including deep brain stimulators, and cardiac and gastric pacemakers, to reduce the burden on patients for long-term use within the body.” To enable wireless battery charging and controls, researchers developed a tiny circuit that integrates a wireless energy harvester with a coil antenna and a Bluetooth low-energy chip. An alternating magnetic field can harmlessly penetrate through tissue, and generate electricity inside the device to charge the battery. Then the battery-powered Bluetooth implant delivers programmable patterns of light to brain cells using an “easy-to-use” smartphone app for real-time brain control. “This device can be operated anywhere and anytime to manipulate neural circuits, which makes it a highly versatile tool for investigating brain functions,” said lead author Choong Yeon Kim, a researcher at KAIST. Neuroscientists successfully tested these implants in rats and demonstrated their ability to suppress cocaine-induced behaviour after the rats were injected with cocaine. This was achieved by precise light stimulation of relevant target neurons in their brains using the smartphone-controlled LEDs. Furthermore, the battery in the implants could be repeatedly recharged while the rats were behaving freely, thus minimizing any physical interruption to the experiments. “Wireless battery re-charging makes experimental procedures much less complicated,” said the co-lead author Min Jeong Ku, a researcher at Yonsei University’s College of Medicine. “The fact that we can control a specific behaviour of animals, by delivering light stimulation into the brain just with a simple manipulation of smartphone app, watching freely moving animals nearby, is very interesting and stimulates a lot of imagination,” said Jeong-Hoon Kim, a professor of physiology at Yonsei University’s College of Medicine. “This technology will facilitate various avenues of brain research.” The researchers believe this brain implant technology may lead to new opportunities for brain research and therapeutic intervention to treat diseases in the brain and other organs. This work was supported by grants from the National Research Foundation of Korea and the KAIST Global Singularity Research Program. -Profile Professor Jae-Woong Jeong https://www.jeongresearch.org/ School of Electrical Engineering KAIST
2021.01.26
View 23379
Expanding the Biosynthetic Pathway via Retrobiosynthesis
- Researchers reports a new strategy for the microbial production of multiple short-chain primary amines via retrobiosynthesis. - KAIST metabolic engineers presented the bio-based production of multiple short-chain primary amines that have a wide range of applications in chemical industries for the first time. The research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering designed the novel biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step. The research team verified the newly designed pathways by confirming the in vivo production of 10 short-chain primary amines by supplying the precursors. Furthermore, the platform Escherichia coli strains were metabolically engineered to produce three proof-of-concept short-chain primary amines from glucose, demonstrating the possibility of the bio-based production of diverse short-chain primary amines from renewable resources. The research team said this study expands the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple short-chain primary amines as examples. Currently, most of the industrial chemicals used in our daily lives are produced with petroleum-based products. However, there are several serious issues with the petroleum industry such as the depletion of fossil fuel reserves and environmental problems including global warming. To solve these problems, the sustainable production of industrial chemicals and materials is being explored with microorganisms as cell factories and renewable non-food biomass as raw materials for alternative to petroleum-based products. The engineering of these microorganisms has increasingly become more efficient and effective with the help of systems metabolic engineering – a practice of engineering the metabolism of a living organism toward the production of a desired metabolite. In this regard, the number of chemicals produced using biomass as a raw material has substantially increased. Although the scope of chemicals that are producible using microorganisms continues to expand through advances in systems metabolic engineering, the biological production of short-chain primary amines has not yet been reported despite their industrial importance. Short-chain primary amines are the chemicals that have an alkyl or aryl group in the place of a hydrogen atom in ammonia with carbon chain lengths ranging from C1 to C7. Short-chain primary amines have a wide range of applications in chemical industries, for example, as a precursor for pharmaceuticals (e.g., antidiabetic and antihypertensive drugs), agrochemicals (e.g., herbicides, fungicides and insecticides), solvents, and vulcanization accelerators for rubber and plasticizers. The market size of short-chain primary amines was estimated to be more than 4 billion US dollars in 2014. The main reason why the bio-based production of short-chain primary amines was not yet possible was due to their unknown biosynthetic pathways. Therefore, the team designed synthetic biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step. The retrobiosynthesis allowed the systematic design of a biosynthetic pathway for short-chain primary amines by using a set of biochemical reaction rules that describe chemical transformation patterns between a substrate and product molecules at an atomic level. These multiple precursors predicted for the possible biosynthesis of each short-chain primary amine were sequentially narrowed down by using the precursor selection step for efficient metabolic engineering experiments. “Our research demonstrates the possibility of the renewable production of short-chain primary amines for the first time. We are planning to increase production efficiencies of short-chain primary amines. We believe that our study will play an important role in the development of sustainable and eco-friendly bio-based industries and the reorganization of the chemical industry, which is mandatory for solving the environmental problems threating the survival of mankind,” said Professor Lee. This paper titled “Microbial production of multiple short-chain primary amines via retrobiosynthesis” was published in Nature Communications. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea. -Publication Dong In Kim, Tong Un Chae, Hyun Uk Kim, Woo Dae Jang, and Sang Yup Lee. Microbial production of multiple short-chain primary amines via retrobiosynthesis. Nature Communications ( https://www.nature.com/articles/s41467-020-20423-6) -Profile Distinguished Professor Sang Yup Lee leesy@kaist.ac.kr Metabolic &Biomolecular Engineering National Research Laboratory http://mbel.kaist.ac.kr Department of Chemical and Biomolecular Engineering KAIST
2021.01.14
View 10325
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