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KAIST Develops Virtual Staining Technology for 3D Histopathology
Moving beyond traditional methods of observing thinly sliced and stained cancer tissues, a collaborative international research team led by KAIST has successfully developed a groundbreaking technology. This innovation uses advanced optical techniques combined with an artificial intelligence-based deep learning algorithm to create realistic, virtually stained 3D images of cancer tissue without the need for serial sectioning nor staining. This breakthrough is anticipated to pave the way for next-generation non-invasive pathological diagnosis.
< Photo 1. (From left) Juyeon Park (Ph.D. Candidate, Department of Physics), Professor YongKeun Park (Department of Physics) (Top left) Professor Su-Jin Shin (Gangnam Severance Hospital), Professor Tae Hyun Hwang (Vanderbilt University School of Medicine) >
KAIST (President Kwang Hyung Lee) announced on the 26th that a research team led by Professor YongKeun Park of the Department of Physics, in collaboration with Professor Su-Jin Shin's team at Yonsei University Gangnam Severance Hospital, Professor Tae Hyun Hwang's team at Mayo Clinic, and Tomocube's AI research team, has developed an innovative technology capable of vividly displaying the 3D structure of cancer tissues without separate staining.
For over 200 years, conventional pathology has relied on observing cancer tissues under a microscope, a method that only shows specific cross-sections of the 3D cancer tissue. This has limited the ability to understand the three-dimensional connections and spatial arrangements between cells.
To overcome this, the research team utilized holotomography (HT), an advanced optical technology, to measure the 3D refractive index information of tissues. They then integrated an AI-based deep learning algorithm to successfully generate virtual H&E* images.* H&E (Hematoxylin & Eosin): The most widely used staining method for observing pathological tissues. Hematoxylin stains cell nuclei blue, and eosin stains cytoplasm pink.
The research team quantitatively demonstrated that the images generated by this technology are highly similar to actual stained tissue images. Furthermore, the technology exhibited consistent performance across various organs and tissues, proving its versatility and reliability as a next-generation pathological analysis tool.
< Figure 1. Comparison of conventional 3D tissue pathology procedure and the 3D virtual H&E staining technology proposed in this study. The traditional method requires preparing and staining dozens of tissue slides, while the proposed technology can reduce the number of slides by up to 10 times and quickly generate H&E images without the staining process. >
Moreover, by validating the feasibility of this technology through joint research with hospitals and research institutions in Korea and the United States, utilizing Tomocube's holotomography equipment, the team demonstrated its potential for full-scale adoption in real-world pathological research settings.
Professor YongKeun Park stated, "This research marks a major advancement by transitioning pathological analysis from conventional 2D methods to comprehensive 3D imaging. It will greatly enhance biomedical research and clinical diagnostics, particularly in understanding cancer tumor boundaries and the intricate spatial arrangements of cells within tumor microenvironments."
< Figure 2. Results of AI-based 3D virtual H&E staining and quantitative analysis of pathological tissue. The virtually stained images enabled 3D reconstruction of key pathological features such as cell nuclei and glandular lumens. Based on this, various quantitative indicators, including cell nuclear distribution, volume, and surface area, could be extracted. >
This research, with Juyeon Park, a student of the Integrated Master’s and Ph.D. Program at KAIST, as the first author, was published online in the prestigious journal Nature Communications on May 22.
(Paper title: Revealing 3D microanatomical structures of unlabeled thick cancer tissues using holotomography and virtual H&E staining.
[https://doi.org/10.1038/s41467-025-59820-0]
This study was supported by the Leader Researcher Program of the National Research Foundation of Korea, the Global Industry Technology Cooperation Center Project of the Korea Institute for Advancement of Technology, and the Korea Health Industry Development Institute.
2025.05.26 View 212 -
<Big Coins> Exhibition: Where Coins and Imagination Collide - Held at SUPEX Hall, KAIST Seoul Campus
KAIST (President Kwang-Hyung Lee) announced on May 19th the opening of the solo exhibition, “Big Coins,” by photographer and media artist Hojun Ji (Adjunct Professor, Department of Industrial Design) at the SUPEX Hall in the Business School of the Seoul Campus. The exhibition will run from May 19th to the end of February of the following year.
This exhibition at the KAIST Seoul Campus Business School presents artworks with an insightful perspective, inviting diverse interpretations from the audience. Notable pieces include ‘Priced,’ which juxtaposes Leonardo da Vinci's ‘Salvator Mundi,’ sold for approximately 450 million US dollars at a 2017 auction, with a Vatican coin bearing the image of Pope John XXIII. Another work, ‘Ciphered,’ superimposes a code used by the German army during World War II onto a Swiss coin featuring Helvetia.
< Priced, 150x150cm, 2025 >
Currently, Hojun Ji, an Adjunct Professor in KAIST’s Department of Industrial Design (and a student at the KAIST Graduate School of Culture Technology), creates his art using images captured by observing everyday objects through optical or electron microscopes.
He has garnered particular attention for his unique artistic world, which combines enlarged microscopic photographs of coins from across the globe with significant news articles from modern and contemporary history.
Yeo-sun Yoon, Dean of the College of Business Administration, commented, “While the KAIST Art Museum is located at the main campus in Daejeon, the College of Business Administration here on the Seoul Campus also regularly hosts exhibitions curated by the museum. I am delighted to encounter a new realm of art through this solo exhibition by Artist Hojun Ji.”
< Ciphered, 150x150cm, 2025 >
Hyeon-Jeong Suk, Director of the Art Museum and a Full Professor in KAIST’s Department of Industrial Design, remarked, “Professor Hojun Ji's experimental imagination is remarkably unique and eccentric. As a graduate student, he connected data from his observations of his lab dog’s droppings with Jeong Seon's <Geumgang Jeondo>. Such imaginative thinking exemplifies the direction KAIST is pursuing.”
Artist Hojun Ji stated, “The coins I examined through optical and electron microscopes were not merely a form of payment but rather portraits of humanity etched with time and power. The history and memories embedded in their fine cracks and textures resonated with me as a singular sculpture. I aim to unlock the vast world of imagination concealed within these small pieces of metal.”
< Geumgang Byeondo: a Variation of the View of Mt. Geumgang (a twist of Geumgang Jeondo - a Complete View of Geumgangsan Mountain, 1734), 80x120cm, 2009 >
Ji has presented experimental works that transcend the boundaries of science and art through numerous exhibitions both domestically and internationally. His work has also been featured on the cover of the international academic journal Digital Creativity and is increasingly recognized for its artistic merit, with pieces housed in the Embassy of the Republic of Korea in Turkey, the Seoul Museum of Art, and the 9/11 Memorial Center in the United States.
This solo exhibition, which will continue until the end of February of next year, is open to KAIST members and external visitors free of charge.
2025.05.20 View 321 -
Decoding Fear: KAIST Identifies An Affective Brain Circuit Crucial for Fear Memory Formation by Non-nociceptive Threat Stimulus
Fear memories can form in the brain following exposure to threatening situations such as natural disasters, accidents, or violence. When these memories become excessive or distorted, they can lead to severe mental health disorders, including post-traumatic stress disorder (PTSD), anxiety disorders, and depression. However, the mechanisms underlying fear memory formation triggered by affective pain rather than direct physical pain have remained largely unexplored – until now.
A KAIST research team has identified, for the first time, a brain circuit specifically responsible for forming fear memories in the absence of physical pain, marking a significant advance in understanding how psychological distress is processed and drives fear memory formation in the brain. This discovery opens the door to the development of targeted treatments for trauma-related conditions by addressing the underlying neural pathways.
< Photo 1. (from left) Professor Jin-Hee Han, Dr. Junho Han and Ph.D. Candidate Boin Suh of the Department of Biological Sciences >
KAIST (President Kwang-Hyung Lee) announced on May 15th that the research team led by Professor Jin-Hee Han in the Department of Biological Sciences has identified the pIC-PBN circuit*, a key neural pathway involved in forming fear memories triggered by psychological threats in the absence of sensory pain. This groundbreaking work was conducted through experiments with mice.*pIC–PBN circuit: A newly identified descending neural pathway from the posterior insular cortex (pIC) to the parabrachial nucleus (PBN), specialized for transmitting psychological threat information.
Traditionally, the lateral parabrachial nucleus (PBN) has been recognized as a critical part of the ascending pain pathway, receiving pain signals from the spinal cord. However, this study reveals a previously unknown role for the PBN in processing fear induced by non-painful psychological stimuli, fundamentally changing our understanding of its function in the brain.
This work is considered the first experimental evidence that 'emotional distress' and 'physical pain' are processed through different neural circuits to form fear memories, making it a significant contribution to the field of neuroscience. It clearly demonstrates the existence of a dedicated pathway (pIC-PBN) for transmitting emotional distress.
The study's first author, Dr. Junho Han, shared the personal motivation behind this research: “Our dog, Lego, is afraid of motorcycles. He never actually crashed into one, but ever since having a traumatizing event of having a motorbike almost run into him, just hearing the sound now triggers a fearful response. Humans react similarly – even if you didn’t have a personal experience of being involved in an accident, a near-miss or exposure to alarming media can create lasting fear memories, which may eventually lead to PTSD.”
He continued, “Until now, fear memory research has mainly relied on experimental models involving physical pain. However, much of real-world human fears arise from psychological threats, rather than from direct physical harm. Despite this, little was known about the brain circuits responsible for processing these psychological threats that can drive fear memory formation.”
To investigate this, the research team developed a novel fear conditioning model that utilizes visual threat stimuli instead of electrical shocks. In this model, mice were exposed to a rapidly expanding visual disk on a ceiling screen, simulating the threat of an approaching predator. This approach allowed the team to demonstrate that fear memories can form in response to a non-nociceptive, psychological threat alone, without the need for physical pain.
< Figure 1. Artificial activation of the posterior insular cortex (pIC) to lateral parabrachial nucleus (PBN) neural circuit induces anxiety-like behaviors and fear memory formation in mice. >
Using advanced chemogenetic and optogenetic techniques, the team precisely controlled neuronal activity, revealing that the lateral parabrachial nucleus (PBN) is essential to form fear memories in response to visual threats. They further traced the origin of these signals to the posterior insular cortex (pIC), a region known to process negative emotions and pain, confirming a direct connection between the two areas.
The study also showed that inhibiting the pIC–PBN circuit significantly reduced fear memory formation in response to visual threats, without affecting innate fear responses or physical pain-based learning. Conversely, artificially activating this circuit alone was sufficient to drive fear memory formation, confirming its role as a key pathway for processing psychological threat information.
< Figure 2. Schematic diagram of brain neural circuits transmitting emotional & physical pain threat signals. Visual threat stimuli do not involve physical pain but can create an anxious state and form fear memory through the affective pain signaling pathway. >
Professor Jin-Hee Han commented, “This study lays an important foundation for understanding how emotional distress-based mental disorders, such as PTSD, panic disorder, and anxiety disorder, develop, and opens new possibilities for targeted treatment approaches.”
The findings, authored by Dr. Junho Han (first author), Ph.D. candidate Boin Suh (second author), and Dr. Jin-Hee Han (corresponding author) of the Department of Biological Sciences, were published online in the international journal Science Advances on May 9, 2025.※ Paper Title: A top-down insular cortex circuit crucial for non-nociceptive fear learning. Science Advances (https://doi.org/10.1101/2024.10.14.618356)※ Author Information: Junho Han (first author), Boin Suh (second author), and Jin-Hee Han (corresponding author)
This research was supported by grants from the National Research Foundation of Korea (NRF-2022M3E5E8081183 and NRF-2017M3C7A1031322).
2025.05.15 View 747 -
KAIST Discovers Protein Switch that Turns Anti-Viral Immune Response On and Off
Even after the COVID-19 pandemic, various new infectious diseases continue to emerge, posing ongoing viral threats that demand robust and sustained immune defenses. However, excessive immune reactions can also harm body tissues, causing significant health issues. KAIST and an international research team have discovered a critical protein that acts as a 'switch' regulating immune responses to viruses. This breakthrough is expected to lay the groundwork for future infectious disease responses and autoimmune disease treatment strategies.
KAIST (President Kwang-Hyung Lee) announced on May 14 that a joint research team led by Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering at KAIST and Professor Seunghee Cha from University of Florida has discovered the mechanism by which double-stranded RNA derived from mitochondria amplifies immune responses. They identified the protein SLIRP as an 'immune switch' that regulates this process, playing a crucial role in both viral infections and autoimmune diseases.
< (From left) Master's candidate Yewon Yang, Professor Yoosik Kim and Ph.D. candidate Doyeong Ku of the Department of Chemical and Biomolecular Engineering >
Autoimmune diseases arise when the immune system fails to differentiate between external pathogens and the body's own molecules, leading to self-directed attacks. Despite extensive research, the precise causes of excessive inflammatory conditions like Sjögren’s syndrome and systemic lupus erythematosus remain unclear, and effective treatments are still limited.
To uncover the molecular mechanisms driving immune hyperactivation and to identify potential regulatory factors, the research team led by Professor Yoosik Kim focused on mitochondrial double-stranded RNA (mt-dsRNA), a genetic immunogenic material produced within cellular organelles. Since mt-dsRNA structurally resembles viral RNA, it can mistakenly trigger immune responses even in the absence of an actual viral infection.
The team discovered that SLIRP, a key regulator of mt-dsRNA, amplifies immune responses by stabilizing the RNA. They confirmed that SLIRP expression increases in experimental models simulating the tissues of autoimmune disease patients and viral infections. Conversely, suppressing SLIRP significantly reduced the immune response, underscoring its role as a critical factor in immune amplification.
This study also demonstrated the dual function of SLIRP in different contexts. In cells infected with human beta coronavirus OC43 and encephalomyocarditis virus (EMCV), SLIRP suppression led to reduced antiviral responses and increased viral replication. Meanwhile, in the blood and salivary gland cells of Sjögren’s syndrome patients, where both SLIRP and mt-dsRNA levels were elevated, suppressing SLIRP alleviated the abnormal immune response.
These findings highlight SLIRP as a key molecular switch that regulates immune responses in both infections and autoimmune diseases.
< Figure 1. Schematic diagram of antiviral signal amplification by SLIRP: SLIRP-based mt-dsRNA induction, cytoplasmic accumulation, and strong interferon response induction by positive feedback of immune response activation. Confirmation of the immune regulatory function of SLIRP in defense against autoimmune diseases Sjögren's syndrome, coronavirus, and encephalomyocarditis virus infection. >
Professor Yoosik Kim remarked, "Through this study, we have identified SLIRP as a crucial protein that drives immune amplification via mt-dsRNAs. Given its dual role in autoimmune diseases and viral infections, SLIRP presents a promising target for immune regulation therapies across various inflammatory disease contexts."
The study, with Ph.D. student Do-Young Ku (first author) and M.S. student Ye-Won Yang (second author) from the Department of Chemical and Biomolecular Engineering at KAIST as primary contributors, was published online in the journal Cell Reports on April 19, 2025.
※ Paper title: SLIRP amplifies antiviral signaling via positive feedback regulation and contributes to autoimmune diseases※ Main authors: Do-Young Ku (KAIST, first author), Ye-Won Yang (KAIST, second author), Seunghee Cha (University of Florida, corresponding author), Yoosik Kim (KAIST, corresponding author)
This study was supported by the Ministry of Health and Welfare's Public Health Technology Research Program and the National Institutes of Health (NIH) through Research Project (R01) funding.
2025.05.14 View 690 -
KAIST Identifies Master Regulator Blocking Immunotherapy, Paving the Way for a New Lung Cancer Treatment
Immune checkpoint inhibitors, a class of immunotherapies that help immune cells attack cancer more effectively, have revolutionized cancer treatment. However, fewer than 20% of patients respond to these treatments, highlighting the urgent need for new strategies tailored to both responders and non-responders.
KAIST researchers have discovered that 'DEAD-box helicases 54 (DDX54)', a type of RNA-binding protein, is the master regulator that hinders the effectiveness of immunotherapy—opening a new path for lung cancer treatment. This breakthrough technology has been transferred to faculty startup BioRevert Inc., where it is currently being developed as a companion therapeutic and is expected to enter clinical trials by 2028.
< Photo 1. (From left) Researcher Jungeun Lee, Professor Kwang-Hyun Cho and Postdoctoral Researcher Jeong-Ryeol Gong of the Department of Bio and Brain Engineering at KAIST >
KAIST (represented by President Kwang-Hyung Lee) announced on April 8 that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering had identified DDX54 as a critical factor that determines the immune evasion capacity of lung cancer cells. They demonstrated that suppressing DDX54 enhances immune cell infiltration into tumors and significantly improves the efficacy of immunotherapy.
Immunotherapy using anti-PD-1 or anti-PD-L1 antibodies is considered a powerful approach in cancer treatment. However, its low response rate limits the number of patients who actually benefit.
To identify likely responders, tumor mutational burden (TMB) has recently been approved by the FDA as a key biomarker for immunotherapy. Cancers with high mutation rates are thought to be more responsive to immune checkpoint inhibitors. However, even tumors with high TMB can display an “immune-desert” phenotype—where immune cell infiltration is severely limited—resulting in poor treatment responses.
< Figure 1. DDX54 was identified as the master regulator that induces resistance to immunotherapy by orchestrating suppression of immune cell infiltration through cancer tissues as lung cancer cells become immune-evasive >
Professor Kwang-Hyun Cho's research team compared transcriptome and genome data of lung cancer patients with immune evasion capabilities through gene regulatory network analysis (A) and discovered DDX54, a master regulator that induces resistance to immunotherapy (B-F).
This study is especially significant in that it successfully demonstrated that suppressing DDX54 in immune-desert lung tumors can overcome immunotherapy resistance and improve treatment outcomes.
The team used transcriptomic and genomic data from immune-evasive lung cancer patients and employed systems biology techniques to infer gene regulatory networks. Through this analysis, they identified DDX54 as a central regulator in the immune evasion of lung cancer cells.
In a syngeneic mouse model, the suppression of DDX54 led to significant increases in the infiltration of anti-cancer immune cells such as T cells and NK cells, and greatly improved the response to immunotherapy.
Single-cell transcriptomic and spatial transcriptomic analyses further showed that combination therapy targeting DDX54 promoted the differentiation of T cells and memory T cells that suppress tumors, while reducing the infiltration of regulatory T cells and exhausted T cells that support tumor growth.
< Figure 2. In the syngeneic mouse model made of lung cancer cells, it was confirmed that inhibiting DDX54 reversed the immune-evasion ability of cancer cells and enhanced the sensitivity to anti-PD-1 therapy >
In a syngeneic mouse model made of lung cancer cells exhibiting immunotherapy resistance, the treatment applied after DDX54 inhibition resulted in statistically significant inhibition of lung cancer growth (B-D) and a significant increase in immune cell infiltration into the tumor tissue (E, F).
The mechanism is believed to involve DDX54 suppression inactivating signaling pathways such as JAK-STAT, MYC, and NF-κB, thereby downregulating immune-evasive proteins CD38 and CD47. This also reduced the infiltration of circulating monocytes—which promote tumor development—and promoted the differentiation of M1 macrophages that play anti-tumor roles.
Professor Kwang-Hyun Cho stated, “We have, for the first time, identified a master regulatory factor that enables immune evasion in lung cancer cells. By targeting this factor, we developed a new therapeutic strategy that can induce responsiveness to immunotherapy in previously resistant cancers.”
He added, “The discovery of DDX54—hidden within the complex molecular networks of cancer cells—was made possible through the systematic integration of systems biology, combining IT and BT.”
The study, led by Professor Kwang-Hyun Cho, was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 2, 2025, with Jeong-Ryeol Gong being the first author, Jungeun Lee, a co-first author, and Younghyun Han, a co-author of the article.
< Figure 3. Single-cell transcriptome and spatial transcriptome analysis confirmed that knockdown of DDX54 increased immune cell infiltration into cancer tissues >
In a syngeneic mouse model made of lung cancer cells that underwent immunotherapy in combination with DDX54 inhibition, single-cell transcriptome (H-L) and spatial transcriptome (A-G) analysis of immune cells infiltrating inside cancer tissues were performed. As a result, it was confirmed that anticancer immune cells such as T cells, B cells, and NK cells actively infiltrated the core of lung cancer tissues when DDX54 inhibition and immunotherapy were concurrently administered.
(Paper title: “DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden,” DOI: https://doi.org/10.1073/pnas.2412310122)
This work was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-Career Research Program and Basic Research Laboratory Program.
< Figure 4. The identified master regulator DDX54 was confirmed to induce CD38 and CD47 expression through Jak-Stat3, MYC, and NF-κB activation. >
DDX54 activates the Jak-Stat3, MYC, and NF-κB pathways in lung cancer cells to increase CD38 and CD47 expression (A-G). This creates a cancer microenvironment that contributes to cancer development (H) and ultimately induces immune anticancer treatment resistance.
< Figure 5. It was confirmed that an immune-inflamed environment can be created by combining DDX54 inhibition and immune checkpoint inhibitor (ICI) therapy. >
When DDX54 inhibition and ICI therapy are simultaneously administered, the cancer cell characteristics change, the immune evasion ability is restored, and the environment is transformed into an ‘immune-activated’ environment in which immune cells easily infiltrate cancer tissues. This strengthens the anticancer immune response, thereby increasing the sensitivity of immunotherapy even in lung cancer tissues that previously had low responsiveness to immunotherapy.
2025.04.08 View 2493 -
KAIST Accelerates Synthetic Microbe Design by Discovering Novel Enzymes Using AI
< (From left) Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering (top), Hongkeun Ji, PhD candidate of the Department of Chemical and Biomolecular Engineering (top), Ha Rim Kim, PhD candidate of the Department of Chemical and Biomolecular Engineering, and Dr. Gi Bae Kim of the BioProcess Engineering Research Center >
Enzymes are proteins that catalyze biochemical reactions within cells and play a pivotal role in metabolic processes. Accordingly, identifying the functions of novel enzymes is a critical task in the construction of microbial cell factories.
A KAIST research team has leveraged artificial intelligence (AI) to design novel enzymes that do not exist in nature, significantly accelerating microbial cell factory development and boosting the potential for next-generation biotechnological applications such as drug development and biofuel production.
KAIST (represented by President Kwang-Hyung Lee) announced on the 21st of April that Distinguished Professor Sang Yup Lee and his team from the Department of Chemical and Biomolecular Engineering have published a review titled “Enzyme Functional Classification Using Artificial Intelligence,” which outlines the advancement of AI-based enzyme function prediction technologies and analyzes how AI has contributed to the discovery and design of new enzymes.
Professor Lee’s team systematically reviewed the development of enzyme function prediction technologies utilizing machine learning and deep learning, offering a comprehensive analysis.
From sequence similarity-based prediction methods to the integration of convolutional neural networks (CNNs), recurrent neural networks (RNNs), graph neural networks (GNNs), and transformer-based large language models, the paper covers a broad range of AI applications. It analyzes how these technologies extract meaningful information from protein sequences and enhance prediction accuracy.
In particular, enzyme function prediction using deep learning goes beyond simple sequence similarity analysis. By automatically extracting structural and evolutionary features embedded in amino acid sequences, deep learning enables more precise predictions of catalytic functions.
This highlights the unique advantages of AI models compared to traditional bioinformatics approaches.
Moreover, the review suggests that the advancement of generative AI will move future research beyond predicting existing functions to generating entirely new enzymes with functions not found in nature. This shift is expected to profoundly impact the trajectory of biotechnology and synthetic biology.
< Figure 1. Extraction of enzyme characteristics and function prediction using various deep learning structures >
Ha Rim Kim, a Ph.D. candidate and co-first author from the Department of Chemical and Biomolecular Engineering, stated, “AI-based enzyme function prediction and enzyme design are highly important across various fields including metabolic engineering, synthetic biology, and healthcare.”
Distinguished Professor Sang Yup Lee added, “AI-powered enzyme function prediction shows the potential to solve diverse biological problems and will significantly contribute to accelerating research across the entire field.”
The review was published on March 28 in Trends in Biotechnology, a leading biotechnology journal issued by Cell Press.
※ Title: Enzyme Functional Classification Using Artificial Intelligence
※DOI: https://doi.org/10.1016/j.tibtech.2025.03.003
※ Author Information: Ha Rim Kim (KAIST, Co-first author), Hongkeun Ji (KAIST, Co-first author), Gi Bae Kim (KAIST, Third author), Sang Yup Lee (KAIST, Corresponding author)
This research was supported by the Ministry of Science and ICT under the project Development of Core Technologies for Advanced Synthetic Biology to Lead the Bio-Manufacturing Industry (aimed at replacing petroleum-based chemicals), and also by joint support from the Ministry of Science and ICT and the Ministry of Health and Welfare for the project Development of Novel Antibiotic Structures Using Deep Learning-Based Synthetic Biology.
2025.04.07 View 1382 -
KAIST Innovates Mid-Infrared Photodetectors for Exoplanet Detection, Expanding Applications to Environmental and Medical Fields
NASA’s James Webb Space Telescope (JWST) utilizes mid-infrared spectroscopy to precisely analyze molecular components such as water vapor and sulfur dioxide in exoplanet atmospheres. The key to this analysis, where each molecule exhibits a unique spectral "fingerprint," lies in highly sensitive photodetector technology capable of measuring extremely weak light intensities. Recently, KAIST researchers have developed an innovative photodetector capable of detecting a broad range of mid-infrared spectra, garnering significant attention.
< Photo 1. (from the left) Ph.D. candidate Inki Kim (co-author), Professor SangHyeon Kim (corresponding author), Dr. Joonsup Shim (first author), and Dr. Jinha Lim (co-author) of KAIST School of Electrical Engineering. >
KAIST (represented by President Kwang-Hyung Lee) announced on the 27th of March that a research team led by Professor SangHyeon Kim from the School of Electrical Engineering has developed a mid-infrared photodetector that operates stably at room temperature, marking a major turning point for the commercialization of ultra-compact optical sensors.
The newly developed photodetector utilizes conventional silicon-based CMOS processes, enabling low-cost mass production while maintaining stable operation at room temperature. Notably, the research team successfully demonstrated the real-time detection of carbon dioxide (CO₂) gas using ultra-compact and ultra-thin optical sensors equipped with this photodetector, proving its potential for environmental monitoring and hazardous gas analysis.
Existing mid-infrared photodetectors generally require cooling systems due to high thermal noise at room temperature. These cooling systems increase the size and cost of equipment, making miniaturization and integration into portable devices challenging. Furthermore, conventional mid-infrared photodetectors are incompatible with silicon-based CMOS processes, limiting large-scale production and commercialization.
To address these limitations, the research team developed a waveguide-integrated photodetector using germanium (Ge), a Group IV element like silicon. This approach enables broad-spectrum mid-infrared detection while ensuring stable operation at room temperature.
< Figure 1. Schematic diagram of a room-temperature mid-infrared waveguide-integrated photodetector based on the Ge-on-insulator optical platform proposed in this study (top). Optical microscope image of the integrated photodetector connected with the sensing unit (bottom). >
A waveguide is a structure designed to efficiently guide light along a specific path with minimal loss. To implement various optical functions on a chip (on-chip), the development of waveguide-integrated photodetectors and waveguide-based optical components is essential.
Unlike conventional photodetectors that primarily rely on bandgap absorption principles, this new technology leverages the bolometric effect*, allowing it to detect the entire mid-infrared spectral range. As a result, it can be widely applied to the real-time sensing of various molecular species.
*Bolometric effect: A principle in which light absorption leads to an increase in temperature, causing electrical signals to change accordingly.
The waveguide-integrated mid-infrared photodetector developed by the research team is considered a groundbreaking innovation that overcomes the limitations of existing mid-infrared sensor technologies, including the need for cooling, difficulties in mass production, and high costs.
< Figure 2. Room temperature photoresponse characteristics of the mid-infrared waveguide photodetector proposed in this study (left) and real-time carbon dioxide (CO2) gas sensing results using the photodetector (right). >
This breakthrough technology is expected to be applicable across diverse fields, including environmental monitoring, medical diagnostics, industrial process management, national defense and security, and smart devices. It also paves the way for next-generation mid-infrared sensor advancements.
Professor SangHyeon Kim from KAIST stated, "This research represents a novel approach that overcomes the limitations of existing mid-infrared photodetector technologies and has great potential for practical applications in various fields." He further emphasized, "Since this sensor technology is compatible with CMOS processes, it enables low-cost mass production, making it highly suitable for next-generation environmental monitoring systems and smart manufacturing sites."
< Figure 3. Performance comparison image of a room-temperature mid-infrared waveguide photodetector fabricated with the technology proposed in this study. It achieves the world’s highest performance compared to existing technologies utilizing the Bolometric effect, and is the only solution compatible with CMOS processes. The technology proposed by our research team is characterized by its ability to respond to a wide spectrum of the mid-infrared band without limitations. >
The study, with Dr. Joonsup Shim (currently a postdoctoral researcher at Harvard University) as the first author, was published on March 19, 2025 in the internationally renowned journal Light: Science & Applications (JCR 2.9%, IF=20.6).
(Paper title: “Room-temperature waveguide-integrated photodetector using bolometric effect for mid-infrared spectroscopy applications,” https://doi.org/10.1038/s41377-025-01803-3)
2025.03.27 View 820 -
KAIST Captures Protein Reaction in Just Six Milliseconds
Understanding biomolecular processes - such as protein-protein interactions and enzyme-substrate reactions that occur on the microseconds to millisecond time scale is essential for comprehending life processes and advancing drug development. KAIST researchers have developed a method for freezing and analyzing biochemical reaction dynamics within a span of just a few milliseconds, marking a significant step forward in better understanding complex biological reactions.
< Photo. (From left) Professor Jin Young Kang and Haerang Hwang of the Integrated Master's and Doctoral Program of the Department of Chemistry, along with Professor Wonhee Lee of the Department of Physics >
KAIST (represented by President Kwang Hyung Lee) announced on the 24th of March that a joint research team led by Professor Jin Young Kang from the Department of Chemistry and Professor Wonhee Lee from the Department of Physics has developed a parylene-based thin-film microfluidic mixing-and-spraying device for ultra-fast biochemical reaction studies.
*Parylene: A key material for microfluidic devices used to observe protein dynamics at ultra-high speeds. It can be fabricated into a few micrometer-thick films, which can be used in making a spray nozzle for microfluidic devices.
This research overcomes the limitations of the existing time-resolved cryo-electron microscopy (TRCEM) method by reducing sample consumption to one-third of the conventional amount while improving the minimum time resolution—down to just six milliseconds (6 ms).
TRCEM is a technique that rapidly freezes protein complexes during intermediate reaction stages under cryogenic conditions, which allows researchers to analyze their structures. This approach has gained significant attention recently for its ability to capture transient biochemical events.
< Figure 1. Time-resolved cryo-EM (TRCEM) technique using microfluidic channels. In order to capture the intermediate structure of biomolecules during a biochemical reaction over time, biomolecules and reaction substrates are mixed in a microfluidic channel, and then sprayed on a grid after a certain reaction time and frozen in liquid ethane to prepare a cryo-EM sample. This can then be analyzed by cryo-EM to observe the structural changes of proteins over time. >
Transient intermediate structures of protein complexes could not be captured by traditional cryo-electron microscopy due to their extremely short lifespans. Although several TRCEM techniques have been developed to address this issue, previous methods were hindered by large sample consumption and limited time resolution. To overcome these challenges, the KAIST team developed a new mixing-and-spraying device using ultra-thin parylene films. The integrated design of the device further enhanced the precision and reproducibility of experiments.
< Figure 2. TRCEM grid fabrication setup using a parylene-based thin-film microfluidic device and actual appearance of the device. You can see that a thin-film parylene channel is inserted into the injection nozzle. The integration of the reaction channel and the injection nozzle allowed the residence time in the device to be reduced to at least 0.5 ms. >
“This research makes TRCEM more practical and paves the way for diverse applications of the parylene thin-film device in structural biology, drug development, enzyme reaction studies, and biosensor research.” Professor Jin Young Kang explained, emphasizing the significance of the study.
Professor Wonhee Lee added, “The team aims to continue this research, focusing on improvement of the technique to achieve higher time resolution with minimal sample consumption.”
< Figure 3. Comparison of the spraying patterns of the parylene mixing-jet device and the conventional mixing-jet device and the filament length in the resulting RecA-ssDNA filament formation reaction. It was shown that the thin film spray nozzle structure affects the uniformity and accuracy of the final reaction time. >
The research findings, with Haerang Hwang (a graduate student in the integrated master's and Ph.D. program in the Department of Chemistry) as the first author, were published online on January 28, 2025, in the international journal Advanced Functional Materials. (Paper Title: “Integrated Parylene-Based Thin-Film Microfluidic Device for Time-Resolved Cryo-Electron Microscopy”, DOI: doi.org/10.1002/adfm.202418224)
This research was supported by the National Research Foundation of Korea (NRF), the Samsung Future Technology Development Program, and the CELINE consortium.
2025.03.24 View 1788 -
KAIST Captures Hot Holes: A Breakthrough in Light-to-Electricity Energy Conversion
When light interacts with metallic nanostructures, it instantaneously generates plasmonic hot carriers, which serve as key intermediates for converting optical energy into high-value energy sources such as electricity and chemical energy. Among these, hot holes play a crucial role in enhancing photoelectrochemical reactions. However, they thermally dissipate within picoseconds (trillionths of a second), making practical applications challenging. Now, a Korean research team has successfully developed a method for sustaining hot holes longer and amplifying their flow, accelerating the commercialization of next-generation, high-efficiency, light-to-energy conversion technologies.
KAIST (represented by President Kwang Hyung Lee) announced on the 12th of March that a research team led by Distinguished Professor Jeong Young Park from the Department of Chemistry, in collaboration with Professor Moonsang Lee from the Department of Materials Science and Engineering at Inha University, has successfully amplified the flow of hot holes and mapped local current distribution in real time, thereby elucidating the mechanism of photocurrent enhancement.
The team designed a nanodiode structure by placing a metallic nanomesh on a specialized semiconductor substrate (p-type gallium nitride) to facilitate hot hole extraction at the surface. As a result, in gallium nitride substrates aligned with the hot hole extraction direction, the flow of hot holes was amplified by approximately two times compared to substrates aligned in other directions.
To fabricate the Au nanomesh, a polystyrene nano-bead monolayer assembly was first placed on a gallium nitride (p-GaN) substrate, and then the polystyrene nano-beads were etched to form a nanomesh template (Figure 1A). Then, a 20 nm thick gold nano-film was deposited, and the etched polystyrene nano-beads were removed to realize the gold nano-mesh structure on the GaN substrate (Figure 1B). The fabricated Au nanomesh exhibited strong light absorption in the visible range due to the plasmonic resonance effect (Figure 1C). >
Furthermore, using a photoconductive atomic force microscopy (pc-AFM)-based photocurrent mapping system, the researchers analyzed the flow of hot holes in real time at the nanometer scale (one hundred-thousandth the thickness of a human hair). They observed that hot hole activation was strongest at "hot spots," where light was locally concentrated on the gold nanomesh. However, by modifying the growth direction of the gallium nitride substrate, hot hole activation extended beyond the hot spots to other areas as well.
Through this research, the team discovered an efficient method for converting light into electrical and chemical energy. This breakthrough is expected to significantly advance next-generation solar cells, photocatalysts, and hydrogen production technologies.
Professor Jeong Young Park stated, "For the first time, we have successfully controlled the flow of hot holes using a nanodiode technique. This innovation holds great potential for various optoelectronic devices and photocatalytic applications. For example, it could lead to groundbreaking advancements in solar energy conversion technologies, such as solar cells and hydrogen production. Additionally, the real-time analysis technology we developed can be applied to the development of ultra-miniaturized optoelectronic devices, including optical sensors and nanoscale semiconductor components."
The study was led by Hyunhwa Lee (PhD., KAIST Department of Chemistry) and Yujin Park (Postdoc Researcher, University of Texas at Austin Department of Chemical Engineering) as co-first authors and Professors Moonsang Lee (Inha University, Department of Materials Science and Engineering) and Jeong Young Park (KAIST, Department of Chemistry) serving as corresponding authors. The research findings were published online in Science Advances on March 7.
(Paper Title: “Reconfiguring hot-hole flux via polarity modulation of p-GaN in plasmonic Schottky architectures”, DOI: https://www.science.org/doi/10.1126/sciadv.adu0086)
This research was supported by the National Research Foundation of Korea (NRF).
2025.03.17 View 2485 -
KAIST perfectly reproduces Joseon-era Irworobongdo without pigments
Typically, chemical pigments that absorb specific wavelengths of light within the visible spectrum are required to produce colors. However, KAIST researchers have successfully reproduced the Joseon-era Irworobongdo [일월오봉도] painting using ultra-precise color graphics without any chemical pigments, allowing for the permanent and eco-friendly preservation of color graphics without fading or discoloration.
< (From left) Chaerim Son, a graduate of the Department of Biochemical Engineering (lead author), Seong Kyeong Nam, a graduate of the PhD program, Jiwoo Lee, a PhD student, and Professor Shin-Hyun Kim >
KAIST (represented by President Kwang Hyung Lee) announced on the 26th of February that a research team led by Professor Shinhyun Kim from the Department of Biological and Chemical Engineering had developed a technology that enables high-resolution color graphics without using any chemical pigments by employing hemisphere-shaped microstructures.
Morpho butterflies that are brilliant blue in color or Panther chameleons that change skin color exhibit coloration without chemical pigments, as ordered nanostructures within a material reflect visible light through optical interference. Since structural colors arise from physical structures rather than chemical substances, a single material can produce a wide range of colors.
However, the artificial implementation of structural coloration is highly challenging due to the complexity of creating ordered nanostructures. Additionally, it is difficult to produce a variety of colors and to pattern them precisely into complex designs.
< Figure 1. Principle of structural color expression using micro-hemispheres (left) and method of forming micro-hemisphere patterns based on photolithography (right) >
Professor Kim’s team overcame these challenges by using smooth-surfaced hemispherical microstructures instead of ordered nanostructures, enabling the high-precision patterning of diverse structural colors.
When light enters the inverted hemispherical microstructures, the portion of light entering from the sides undergoes total internal reflection along the curved surface, creating retroreflection. When the hemisphere diameter is approximately 10 micrometers (about one-tenth the thickness of a human hair), light traveling along different reflection paths interferes within the visible spectrum, producing structural coloration.
< Figure 2. “Irworobongdo”, the Painting of the Sun, Moon, and the Five Peaks, reproduced in fingernail size without pigment using approximately 200,000 micro-hemispheres >
The structural color can be tuned by adjusting the size of the hemispheres. By arranging hemispheres of varying sizes, much like mixing paints on a palette, an infinite range of colors can be generated.
To precisely pattern microscale hemispheres of different sizes, the research team employed photolithography* using positive photoresists** commonly used in semiconductor processing. They first patterned photoresists into micropillar structures, then induced reflow*** by heating the material, forming hemispherical microstructures.
*Photolithography: A technique used in semiconductor fabrication to pattern microscale structures.
**Positive photoresist: A photosensitive polymer that dissolves more easily in a developer solution after exposure to ultraviolet light.
***Reflow: A process in which a polymer material softens and reshapes into a curved structure when heated.
This method enables the formation of hemisphere-shaped microstructures with the desired sizes and colors in a single-step fabrication process. It also allows for the reproduction of arbitrary color graphics using a single material without any pigments.
The ultra-precise color graphics created with this technique can exhibit color variations depending on the angle of incident light or the viewing perspective. The pattern appears colored from one direction while remaining transparent from the opposite side, exhibiting a Janus effect. These structural color graphics achieve resolution comparable to cutting-edge LED displays, allowing complex color images to be captured within a fingernail-sized area and projected onto large screens.
< Figure 3. “Irworobongdo” that displays different shades depending on the angle of light and viewing direction >
Professor Shinhyun Kim, who led the research, stated, “Our newly developed pigment-free color graphics technology can serve as an innovative method for artistic expression, merging art with advanced materials. Additionally, it holds broad application potential in optical devices and sensors, anti-counterfeiting materials, aesthetic photocard printing, and many other fields.”
This research, with KAIST researcher Chaerim Son as the first author, was published in the prestigious materials science journal Advanced Materials on February 5.
(Paper title: “Retroreflective Multichrome Microdome Arrays Created by Single-Step Reflow”, DOI: 10.1002/adma.202413143 )
< Figure 4. Famous paintings reproduced without pigment: “Impression, Sunrise” (left), “Girl with a Pearl Earring” (right) >
The study was supported by the National Research Foundation of Korea through the Pioneer Converging Technology R&D Program and the Mid-Career Researcher Program.
2025.02.26 View 2435 -
KAIST achieves quantum entanglement essential for quantum error correction
Quantum computing is a technology capable of solving complex problems that classical computers struggle with. To perform accurate computations, quantum computers must correct errors that arise during operations. However, generating the quantum entanglement necessary for quantum error correction has long been considered a major challenge.
< Photo 1. (From left) Students Young-Do Yoon and Chan Roh of the Master's and Doctoral Integrated Program of the Department of Physics poses with Professor Young-Sik Ra and Student Geunhee Gwak of the same program >
KAIST (represented by President Kwang Hyung Lee) announced on the 25th of February that a research team led by Professor Young-Sik Ra from the Department of Physics has successfully implemented a three-dimensional cluster quantum entangled state, a key component for quantum error correction, through experimental demonstration.
Measurement-based quantum computing is an emerging paradigm that implements quantum computations by measuring specially entangled cluster states. The core of this approach lies in the generation of these cluster quantum entangled states, with two-dimensional cluster states commonly used for universal quantum computing.
However, to advance towards fault-tolerant quantum computing, which can correct quantum errors occurring during computations, a more complex three-dimensional cluster state is required. While previous studies have reported the generation of two-dimensional cluster states, experimental implementation of the three-dimensional cluster states necessary for fault-tolerant quantum computing had remained elusive due to the extreme complexity of their entanglement structure.
< Figure 1. (a) Experimental schematic. A pulse laser with a wavelength of 800 nm is converted into a pulse laser with a wavelength of 400 nm through second harmonic generation, and this is incident on a nonlinear crystal (PPKTP) to generate multiple quantum entanglement sources. (b) Generation of a 3D cluster state through optical mode basis change >
The research team overcame this challenge by developing a technique to control femtosecond time-frequency modes, successfully generating a three-dimensional cluster quantum entangled state for the first time.
The team directed a femtosecond laser into a nonlinear crystal, simultaneously generating quantum light sources across multiple frequency modes. (A femtosecond laser is a device that emits ultrashort, high-intensity light pulses.) Using this approach, they successfully created a three-dimensional cluster quantum entangled state.
Professor Young-Sik Ra noted, “This study marks the first successful demonstration of a three-dimensional cluster quantum entangled state, which was previously difficult to achieve with existing technology. This breakthrough is expected to serve as a crucial stepping stone for future research in measurement-based and fault-tolerant quantum computing.”
< Figure 2. Results of 3D cluster state generation. (a) Nullifier measurement of the cluster state. (b) 3D cluster state reconstructed using quantum state tomography. (c) Confirmation of quantum entanglement characteristics of the 3D cluster state >
The study was published online in Nature Photonics on February 24, 2025. The first author is Chan Roh, a Ph.D. candidate in KAIST’s integrated master’s and doctoral program, with Geunhee Gwak and Youngdo Yoon contributing as co-authors. (Paper title: “Generation of Three-Dimensional Cluster Entangled State”, DOI: 10.1038/s41566-025-01631-2)
This research was supported by the National Research Foundation of Korea (Quantum Computing Technology Development Program, Mid-Career Researcher Support Program, and Quantum Simulator for Materials Innovation Program), the Institute for Information & Communications Technology Planning & Evaluation (Quantum Internet Core Technology Program, University ICT Research Center Support Program), and the U.S. Air Force Research Laboratory.
2025.02.25 View 1655 -
Ultralight advanced material developed by KAIST and U of Toronto
< (From left) Professor Seunghwa Ryu of KAIST Department of Mechanical Engineering, Professor Tobin Filleter of the University of Toronto, Dr. Jinwook Yeo of KAIST, and Dr. Peter Serles of the University of Toronto >
Recently, in advanced industries such as automobiles, aerospace, and mobility, there has been increasing demand for materials that achieve weight reduction while maintaining excellent mechanical properties. An international joint research team has developed an ultralight, high-strength material utilizing nanostructures, presenting the potential for various industrial applications through customized design in the future.
KAIST (represented by President Kwang Hyung Lee) announced on the 18th of February that a research team led by Professor Seunghwa Ryu from the Department of Mechanical Engineering, in collaboration with Professor Tobin Filleter from the University of Toronto, has developed a nano-lattice structure that maximizes lightweight properties while maintaining high stiffness and strength.
In this study, the research team optimized the beam shape of the lattice structure to maintain its lightweight characteristics while maximizing stiffness and strength.
Particularly, using a multi-objective Bayesian optimization algorithm*, the team conducted an optimal design process that simultaneously considers tensile and shear stiffness improvement and weight reduction. They demonstrated that the optimal lattice structure could be predicted and designed with significantly less data (about 400 data points) compared to conventional methods.
*Multi-objective Bayesian optimization algorithm: A method that finds the optimal solution while considering multiple objectives simultaneously. It efficiently collects data and predicts results even under conditions of uncertainty.
< Figure 1. Multi-objective Bayesian optimization for generative design of carbon nanolattices with high compressive stiffness and strength at low density. The upper is the illustration of process workflow. The lower part shows top four MBO CFCC geometries with their 2D Bézier curves. (The optimized structure is predicted and designed with much less data (approximately 400) than the conventional method >
Furthermore, to maximize the effect where mechanical properties improve as size decreases at the nanoscale, the research team utilized pyrolytic carbon* material to implement an ultralight, high-strength, high-stiffness nano-lattice structure.
*Pyrolytic carbon: A carbon material obtained by decomposing organic substances at high temperatures. It has excellent heat resistance and strength, making it widely used in industries such as semiconductor equipment coatings and artificial joint coatings, where it must withstand high temperatures without deformation.
For this, the team applied two-photon polymerization (2PP) technology* to precisely fabricate complex nano-lattice structures, and mechanical performance evaluations confirmed that the developed structure simultaneously possesses strength comparable to steel and the lightness of Styrofoam.
*Two-photon polymerization (2PP) technology: An advanced optical manufacturing technique based on the principle that polymerization occurs only when two photons of a specific wavelength are absorbed simultaneously.
Additionally, the research team demonstrated that multi-focus two-photon polymerization (multi-focus 2PP) technology enables the fabrication of millimeter-scale structures while maintaining nanoscale precision.
Professor Seunghwa Ryu explained, "This technology innovatively solves the stress concentration issue, which has been a limitation of conventional design methods, through three-dimensional nano-lattice structures, achieving both ultralight weight and high strength in material development."
< Figure 2. FESEM image of the fabricated nano-lattice structure and (bottom right) the macroscopic nanolattice resting on a bubble >
He further emphasized, "By integrating data-driven optimal design with precision 3D printing technology, this development not only meets the demand for lightweight materials in the aerospace and automotive industries but also opens possibilities for various industrial applications through customized design."
This study was led by Dr. Peter Serles of the Department of Mechanical & Industrial Engineering at University of Toronto and Dr. Jinwook Yeo from KAIST as co-first authors, with Professor Seunghwa Ryu and Professor Tobin Filleter as corresponding authors.
The research was published on January 23, 2025 in the international journal Advanced Materials (Paper title: “Ultrahigh Specific Strength by Bayesian Optimization of Lightweight Carbon Nanolattices”).
DOI: https://doi.org/10.1002/adma.202410651
This research was supported by the Multiphase Materials Innovation Manufacturing Research Center (an ERC program) funded by the Ministry of Science and ICT, the M3DT (Medical Device Digital Development Tool) project funded by the Ministry of Food and Drug Safety, and the KAIST International Collaboration Program.
2025.02.18 View 2929