Park
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KAIST Succeeds in the Real-time Observation of Organoids using Holotomography
Organoids, which are 3D miniature organs that mimic the structure and function of human organs, play an essential role in disease research and drug development. A Korean research team has overcome the limitations of existing imaging technologies, succeeding in the real-time, high-resolution observation of living organoids.
KAIST (represented by President Kwang Hyung Lee) announced on the 14th of October that Professor YongKeun Park’s research team from the Department of Physics, in collaboration with the Genome Editing Research Center (Director Bon-Kyoung Koo) of the Institute for Basic Science (IBS President Do-Young Noh) and Tomocube Inc., has developed an imaging technology using holotomography to observe live, small intestinal organoids in real time at a high resolution.
Existing imaging techniques have struggled to observe living organoids in high resolution over extended periods and often required additional treatments like fluorescent staining.
< Figure 1. Overview of the low-coherence HT workflow. Using holotomography, 3D morphological restoration and quantitative analysis of organoids can be performed. In order to improve the limited field of view, which is a limitation of the microscope, our research team utilized a large-area field of view combination algorithm and made a 3D restoration by acquiring multi-focus holographic images for 3D measurements. After that, the organoids were compartmentalized to divide the parts necessary for analysis and quantitatively evaluated the protein concentration measurable from the refractive index and the survival rate of the organoids. >
The research team introduced holotomography technology to address these issues, which provides high-resolution images without the need for fluorescent staining and allows for the long-term observation of dynamic changes in real time without causing cell damage.
The team validated this technology using small intestinal organoids from experimental mice and were able to observe various cell structures inside the organoids in detail. They also captured dynamic changes such as growth processes, cell division, and cell death in real time using holotomography.
Additionally, the technology allowed for the precise analysis of the organoids' responses to drug treatments, verifying the survival of the cells.
The researchers believe that this breakthrough will open new horizons in organoid research, enabling the greater utilization of organoids in drug development, personalized medicine, and regenerative medicine.
Future research is expected to more accurately replicate the in vivo environment of organoids, contributing significantly to a more detailed understanding of various life phenomena at the cellular level through more precise 3D imaging.
< Figure 2. Real-time organoid morphology analysis. Using holotomography, it is possible to observe the lumen and villus development process of intestinal organoids in real time, which was difficult to observe with a conventional microscope. In addition, various information about intestinal organoids can be obtained by quantifying the size and protein amount of intestinal organoids through image analysis. >
Dr. Mahn Jae Lee, a graduate of KAIST's Graduate School of Medical Science and Engineering, currently at Chungnam National University Hospital and the first author of the paper, commented, "This research represents a new imaging technology that surpasses previous limitations and is expected to make a major contribution to disease modeling, personalized treatments, and drug development research using organoids."
The research results were published online in the international journal Experimental & Molecular Medicine on October 1, 2024, and the technology has been recognized for its applicability in various fields of life sciences. (Paper title: “Long-term three-dimensional high-resolution imaging of live unlabeled small intestinal organoids via low-coherence holotomography”)
This research was supported by the National Research Foundation of Korea, KAIST Institutes, and the Institute for Basic Science.
2024.10.14 View 881 -
KAIST Changes the Paradigm of Drug Discovery with World's First Atomic Editing
In pioneering drug development, the new technology that enables the easy and rapid editing of key atoms responsible for drug efficacy has been regarded as a fundamental and "dream" technology, revolutionizing the process of discovering potential drug candidates. KAIST researchers have become the first in the world to successfully develop single-atom editing technology that maximizes drug efficacy.
On October 8th, KAIST (represented by President Kwang-Hyung Lee) announced that Professor Yoonsu Park’s research team from the Department of Chemistry successfully developed technology that enables the easy editing and correction of oxygen atoms in furan compounds into nitrogen atoms, directly converting them into pyrrole frameworks, which are widely used in pharmaceuticals.
< Image. Conceptual image illustrating the main idea of the research >
This research was published in the prestigious scientific journal Science on October 3rd under the title "Photocatalytic Furan-to-Pyrrole Conversion."
Many drugs have complex chemical structures, but their efficacy is often determined by a single critical atom. Atoms like oxygen and nitrogen play a central role in enhancing the pharmacological effects of these drugs, particularly against viruses.
This phenomenon, where the introduction of specific atoms into a drug molecule dramatically affects its efficacy, is known as the "Single Atom Effect." In leading-edge drug development, discovering atoms that maximize drug efficacy is key.
However, evaluating the Single Atom Effect has traditionally required multi-step, costly synthesis processes, as it has been difficult to selectively edit single atoms within stable ring structures containing oxygen or nitrogen.
Professor Park’s team overcame this challenge by introducing a photocatalyst that uses light energy. They developed a photocatalyst that acts as a “molecular scissor,” freely cutting and attaching five-membered rings, enabling single-atom editing at room temperature and atmospheric pressure—a world first.
The team discovered a new reaction mechanism in which the excited molecular scissor removes oxygen from furan via single-electron oxidation and then sequentially adds a nitrogen atom.
Donghyeon Kim and Jaehyun You, the study's first authors and candidates in KAIST’s integrated master's and doctoral program in the Department of Chemistry, explained that this technique offers high versatility by utilizing light energy to replace harsh conditions. They further noted that the technology enables selective editing, even when applied to complex natural products or pharmaceuticals. Professor Yoonsu Park, who led the research, remarked, "This breakthrough, which allows for the selective editing of five-membered organic ring structures, will open new doors for building libraries of drug candidates, a key challenge in pharmaceuticals. I hope this foundational technology will be used to revolutionize the drug development process."
The significance of this research was highlighted in the Perspective section of Science, a feature where a peer scientist of prominence outside of the project group provides commentary on an impactful research.
This research was supported by the National Research Foundation of Korea’s Creative Research Program, the Cross-Generation Collaborative Lab Project at KAIST, and the POSCO Science Fellowship of the POSCO TJ Park Foundation.
2024.10.11 View 1343 -
Professor Jimin Park and Dr. Inho Kim join the ranks of the 2024 "35 Innovators Under 35" by the MIT Technology Review
< (From left) Professor Jimin Park of the Department of Chemical and Biomolecular Engineering and Dr. Inho Kim, a graduate of the Department of Materials Science and Engineering >
KAIST (represented by President Kwang-Hyung Lee) announced on the 13th of September that Professor Jimin Park from KAIST’s Department of Chemical and Biomolecular Engineering and Dr. Inho Kim, a graduate from the Department of Materials Science and Engineering (currently a postdoctoral researcher at Caltech), were selected by the MIT Technology Review as the 2024 "35 Innovators Under 35”.
The MIT Technology Review, first published in 1899 by the Massachusetts Institute of Technology, is the world’s oldest and most influential magazine on science and technology, offering in-depth analysis across various technology fields, expanding knowledge and providing insights into cutting-edge technology trends.
Since 1999, the magazine has annually named 35 innovators under the age of 35, recognizing young talents making groundbreaking contributions in modern technology fields. The recognition is globally considered a prestigious honor and a dream for young researchers in the science and technology community.
< Image 1. Introduction for Professor Jimin Park at the Meet 35 Innovators Under 35 Summit 2024 >
Professor Jimin Park is developing next-generation bio-interfaces that link artificial materials with living organisms, and is engaged in advanced research in areas such as digital healthcare and carbon-neutral compound manufacturing technologies. In 2014, Professor Park was also recognized as one of the ‘Asia Pacific Innovators Under 35’ by the MIT Technology Review, which highlights young scientists in the Asia-Pacific region.
Professor Park responded, “It’s a great honor to be named as one of the young innovators by the MIT Technology Review, a symbol of innovation with a long history. I will continue to pursue challenging, interdisciplinary research to develop next-generation interfaces that seamlessly connect artificial materials and living organisms, from atomic to system levels.”
< Image 2. Introduction for Dr. Inho Kim as the 2024 Innovator of Materials Science for 35 Innovators Under 35 >
Dr. Inho Kim, who earned his PhD from KAIST in 2020 under the supervision of Professor Sang Ouk Kim from the Department of Materials Science and Engineering, recently succeeded in developing a new artificial muscle using composite fibers. This new material is considered the most human-like muscle ever reported in scientific literature, while also being 17 times stronger than natural human muscle.
Dr. Kim is researching the application of artificial muscle fibers in next-generation wearable assistive devices that move more naturally, like humans or animals, noting that the fibers are lightweight, flexible, and exhibit conductivity during contraction, enabling real-time feedback. Recognized for this potential, Dr. Inho Kim was named one of the '35 Innovators Under 35' this year, making him the first researcher to win the honor with the research conducted at KAIST and a PhD earned from Korea.
Dr. Kim stated, “I aim to develop robots using these new materials that can replace today’s expensive and heavy exoskeleton suits by eliminating motors and rigid frames. This will significantly reduce costs and allow for better customization, making cutting-edge technology more accessible to those who need it most, like children with cerebral palsy.”
2024.09.13 View 1654 -
KAIST presents strategies for Holotomography in advanced bio research
Measuring and analyzing three-dimensional (3D) images of live cells and tissues is considered crucial in advanced fields of biology and medicine. Organoids, which are 3D structures that mimic organs, are particular examples that significantly benefits 3D live imaging. Organoids provide effective alternatives to animal testing in the drug development processes, and can rapidly determine personalized medicine. On the other hand, active researches are ongoing to utilize organoids for organ replacement.
< Figure 1. Schematic illustration of holotomography compared to X-ray CT. Similar to CT, they share the commonality of measuring the optical properties of an unlabeled specimen in three dimensions. Instead of X-rays, holotomography irradiates light in the visible range, and provides refractive index measurements of transparent specimens rather than absorptivity. While CT obtains three-dimensional information only through mechanical rotation of the irradiating light, holotomography can replace this by applying wavefront control technology in the visible range. >
Organelle-level observation of 3D biological specimens such as organoids and stem cell colonies without staining or preprocessing holds significant implications for both innovating basic research and bioindustrial applications related to regenerative medicine and bioindustrial applications.
Holotomography (HT) is a 3D optical microscopy that implements 3D reconstruction analogous to that of X-ray computed tomography (CT). Although HT and CT share a similar theoretical background, HT facilitates high-resolution examination inside cells and tissues, instead of the human body. HT obtains 3D images of cells and tissues at the organelle level without chemical or genetic labeling, thus overcomes various challenges of existing methods in bio research and industry. Its potential is highlighted in research fields where sample physiology must not be disrupted, such as regenerative medicine, personalized medicine, and infertility treatment.
< Figure 2. Label-free 3D imaging of diverse live cells. Time-lapse image of Hep3B cells illustrating subcellular morphology changes upon H2O2 treatment, followed by cellular recovery after returning to the regular cell culture medium. >
This paper introduces the advantages and broad applicability of HT to biomedical researchers, while presenting an overview of principles and future technical challenges to optical researchers. It showcases various cases of applying HT in studies such as 3D biology, regenerative medicine, and cancer research, as well as suggesting future optical development. Also, it categorizes HT based on the light source, to describe the principles, limitations, and improvements of each category in detail. Particularly, the paper addresses strategies for deepening cell and organoid studies by introducing artificial intelligence (AI) to HT.
Due to its potential to drive advanced bioindustry, HT is attracting interest and investment from universities and corporates worldwide. The KAIST research team has been leading this international field by developing core technologies and carrying out key application researches throughout the last decade.
< Figure 3. Various types of cells and organelles that make up the imaging barrier of a living intestinal organoid can be observed using holotomography. >
This paper, co-authored by Dr. Geon Kim from KAIST Research Center for Natural Sciences, Professor Ki-Jun Yoon's team from the Department of Biological Sciences, Director Bon-Kyoung Koo's team from the Institute for Basic Science (IBS) Center for Genome Engineering, and Dr. Seongsoo Lee's team from the Korea Basic Science Institute (KBSI), was published in 'Nature Reviews Methods Primers' on the 25th of July. This research was supported by the Leader Grant and Basic Science Research Program of the National Research Foundation, the Hologram Core Technology Development Grant of the Ministry of Science and ICT, the Nano and Material Technology Development Project, and the Health and Medical R&D Project of the Ministry of Health and Welfare.
2024.07.30 View 1525 -
KAIST builds a high-resolution 3D holographic sensor using a single mask
Holographic cameras can provide more realistic images than ordinary cameras thanks to their ability to acquire 3D information about objects. However, existing holographic cameras use interferometers that measure the wavelength and refraction of light through the interference of light waves, which makes them complex and sensitive to their surrounding environment.
On August 23, a KAIST research team led by Professor YongKeun Park from the Department of Physics announced a new leap forward in 3D holographic imaging sensor technology.
The team proposed an innovative holographic camera technology that does not use complex interferometry. Instead, it uses a mask to precisely measure the phase information of light and reconstruct the 3D information of an object with higher accuracy.
< Figure 1. Structure and principle of the proposed holographic camera. The amplitude and phase information of light scattered from a holographic camera can be measured. >
The team used a mask that fulfills certain mathematical conditions and incorporated it into an ordinary camera, and the light scattered from a laser is measured through the mask and analyzed using a computer. This does not require a complex interferometer and allows the phase information of light to be collected through a simplified optical system. With this technique, the mask that is placed between the two lenses and behind an object plays an important role. The mask selectively filters specific parts of light,, and the intensity of the light passing through the lens can be measured using an ordinary commercial camera. This technique combines the image data received from the camera with the unique pattern received from the mask and reconstructs an object’s precise 3D information using an algorithm.
This method allows a high-resolution 3D image of an object to be captured in any position. In practical situations, one can construct a laser-based holographic 3D image sensor by adding a mask with a simple design to a general image sensor. This makes the design and construction of the optical system much easier. In particular, this novel technology can capture high-resolution holographic images of objects moving at high speeds, which widens its potential field of application.
< Figure 2. A moving doll captured by a conventional camera and the proposed holographic camera. When taking a picture without focusing on the object, only a blurred image of the doll can be obtained from a general camera, but the proposed holographic camera can restore the blurred image of the doll into a clear image. >
The results of this study, conducted by Dr. Jeonghun Oh from the KAIST Department of Physics as the first author, were published in Nature Communications on August 12 under the title, "Non-interferometric stand-alone single-shot holographic camera using reciprocal diffractive imaging".
Dr. Oh said, “The holographic camera module we are suggesting can be built by adding a filter to an ordinary camera, which would allow even non-experts to handle it easily in everyday life if it were to be commercialized.” He added, “In particular, it is a promising candidate with the potential to replace existing remote sensing technologies.”
This research was supported by the National Research Foundation’s Leader Research Project, the Korean Ministry of Science and ICT’s Core Hologram Technology Support Project, and the Nano and Material Technology Development Project.
2023.09.05 View 4266 -
KAIST researchers find the key to overcome the limits in X-ray microscopy
X-ray microscopes have the advantage of penetrating most substances, so internal organs and skeletons can be observed non-invasively through chest X-rays or CT scans. Recently, studies to increase the resolution of X-ray imaging technology are being actively conducted in order to precisely observe the internal structure of semiconductors and batteries at the nanoscale.
KAIST (President Kwang Hyung Lee) announced on April 12th that a joint research team led by Professor YongKeun Park of the Department of Physics and Dr. Jun Lim of the Pohang Accelerator Laboratory has succeeded in developing a core technology that can overcome the resolution limitations of existing X-ray microscopes.
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This study, in which Dr. KyeoReh Lee participated as the first author, was published on 6th of April in “Light: Science and Application”, a world-renowned academic journal in optics and photonics. (Paper title: Direct high-resolution X-ray imaging exploiting pseudorandomness).
X-ray nanomicroscopes do not have refractive lenses. In an X-ray microscope, a circular grating called a concentric zone plate is used instead of a lens. The resolution of an image obtained using the zone plate is determined by the quality of the nanostructure that comprises the plate. There are several difficulties in fabricating and maintaining these nanostructures, which set the limit to the level of resolution for X-ray microscopy.
The research team developed a new X-ray nanomicroscopy technology to overcome this problem. The X-ray lens proposed by the research team is in the form of numerous holes punched in a thin tungsten film, and generates random diffraction patterns by diffracting incident X-rays. The research team mathematically identified that, paradoxically, the high-resolution information of the sample was fully contained in these random diffraction patterns, and actually succeeded in extracting the information and imaging the internal states of the samples.
The imaging method using the mathematical properties of random diffraction was proposed and implemented in the visible light band for the first time by Dr. KyeoReh Lee and Professor YongKeun Park in 2016*. This study uses the results of previous studies to solve the difficult, lingering problem in the field of the X-ray imaging. ※ "Exploiting the speckle-correlation scattering matrix for a compact reference-free holographic image sensor." Nature communications 7.1 (2016): 13359.
The resolution of the image of the constructed sample has no direct correlation with the size of the pattern etched on the random lens used. Based on this idea, the research team succeeded in acquiring images with 14 nm resolution (approximately 1/7 the size of the coronavirus) by using random lenses made in a circular pattern with a diameter of 300 nm.
The imaging technology developed by this research team is a key fundamental technology that can enhance the resolution of X-ray nanomicroscopy, which has been blocked by limitations of the production of existing zone plates.
The first author and one of the co-corresponding author, Dr. KyeoReh Lee of KAIST Department of Physics, said, “In this study, the resolution was limited to 14 nm, but if the next-generation X-ray light source and high-performance X-ray detector are used, the resolution would exceed that of the conventional X-ray nano-imaging and approach the resolution of an electron microscope.” and added, “Unlike an electron microscope, X-rays can observe the internal structure without damaging the sample, so it will be able to present a new standard for non-invasive nanostructure observation processes such as quality inspections for semiconductors.”.
The co-corresponding author, Dr. Jun Lim of the Pohang Accelerator Laboratory, said, “In the same context, the developed image technology is expected to greatly increase the performance in the 4th generation multipurpose radiation accelerator which is set to be established in Ochang of the Northern Chungcheong Province.”
This research was conducted with the support through the Research Leader Program and the Sejong Science Fellowship of the National Research Foundation of Korea.
Fig. 1. Designed diffuser as X-ray imaging lens. a, Schematic of full-field transmission X-ray microscopy. The attenuation (amplitude) map of a sample is measured. The image resolution (dx) is limited by the outermost zone width of the zone plate (D). b, Schematic of the proposed method. A designed diffuser is used instead of a zone plate. The image resolution is finer than the hole size of the diffuser (dx << D).
Fig. 2. The left panel is a surface electron microscopy (SEM) image of the X-ray diffuser used in the experiment. The middle panel shows the design of the X-ray diffuser, and there is an inset in the middle of the panel that shows a corresponding part of the SEM image. The right panel shows an experimental random X-ray diffraction pattern, also known as a speckle pattern, obtained from the X-ray diffuser.
Fig. 3. Images taken from the proposed randomness-based X-ray imaging (bottom) and the corresponding surface electron microscope (SEM) images (top).
2023.04.12 View 4770 -
A Quick but Clingy Creepy-Crawler that will MARVEL You
Engineered by KAIST Mechanics, a quadrupedal robot climbs steel walls and crawls across metal ceilings at the fastest speed that the world has ever seen.
< Photo 1. (From left) KAIST ME Prof. Hae-Won Park, Ph.D. Student Yong Um, Ph.D. Student Seungwoo Hong >
- Professor Hae-Won Park's team at the Department of Mechanical Engineering developed a quadrupedal robot that can move at a high speed on ferrous walls and ceilings.
- It is expected to make a wide variety of contributions as it is to be used to conduct inspections and repairs of large steel structures such as ships, bridges, and transmission towers, offering an alternative to dangerous or risky activities required in hazardous environments while maintaining productivity and efficiency through automation and unmanning of such operations.
- The study was published as the cover paper of the December issue of Science Robotics.
KAIST (President Kwang Hyung Lee) announced on the 26th that a research team led by Professor Hae-Won Park of the Department of Mechanical Engineering developed a quadrupedal walking robot that can move at high speed on steel walls and ceilings named M.A.R.V.E.L. - rightly so as it is a Magnetically Adhesive Robot for Versatile and Expeditious Locomotion as described in their paper, “Agile and Versatile Climbing on Ferromagnetic Surfaces with a Quadrupedal Robot.” (DOI: 10.1126/scirobotics.add1017)
To make this happen, Professor Park's research team developed a foot pad that can quickly turn the magnetic adhesive force on and off while retaining high adhesive force even on an uneven surface through the use of the Electro-Permanent Magnet (EPM), a device that can magnetize and demagnetize an electromagnet with little power, and the Magneto-Rheological Elastomer (MRE), an elastic material made by mixing a magnetic response factor, such as iron powder, with an elastic material, such as rubber, which they mounted on a small quadrupedal robot they made in-house, at their own laboratory. These walking robots are expected to be put into a wide variety of usage, including being programmed to perform inspections, repairs, and maintenance tasks on large structures made of steel, such as ships, bridges, transmission towers, large storage areas, and construction sites.
This study, in which Seungwoo Hong and Yong Um of the Department of Mechanical Engineering participated as co-first authors, was published as the cover paper in the December issue of Science Robotics.
< Image on the Cover of 2022 December issue of Science Robotics >
Existing wall-climbing robots use wheels or endless tracks, so their mobility is limited on surfaces with steps or irregularities. On the other hand, walking robots for climbing can expect improved mobility in obstacle terrain, but have disadvantages in that they have significantly slower moving speeds or cannot perform various movements.
In order to enable fast movement of the walking robot, the sole of the foot must have strong adhesion force and be able to control the adhesion to quickly switch from sticking to the surface or to be off of it. In addition, it is necessary to maintain the adhesion force even on a rough or uneven surface.
To solve this problem, the research team used the EPM and MRE for the first time in designing the soles of walking robots. An EPM is a magnet that can turn on and off the electromagnetic force with a short current pulse. Unlike general electromagnets, it has the advantage that it does not require energy to maintain the magnetic force. The research team proposed a new EPM with a rectangular structure arrangement, enabling faster switching while significantly lowering the voltage required for switching compared to existing electromagnets.
In addition, the research team was able to increase the frictional force without significantly reducing the magnetic force of the sole by covering the sole with an MRE. The proposed sole weighs only 169 g, but provides a vertical gripping force of about *535 Newtons (N) and a frictional force of 445 N, which is sufficient gripping force for a quadrupedal robot weighing 8 kg.
* 535 N converted to kg is 54.5 kg, and 445 N is 45.4 kg. In other words, even if an external force of up to 54.5 kg in the vertical direction and up to 45.4 kg in the horizontal direction is applied (or even if a corresponding weight is hung), the sole of the foot does not come off the steel plate.
MARVEL climbed up a vertical wall at high speed at a speed of 70 cm per second, and was able to walk while hanging upside down from the ceiling at a maximum speed of 50 cm per second. This is the world's fastest speed for a walking climbing robot. In addition, the research team demonstrated that the robot can climb at a speed of up to 35 cm even on a surface that is painted, dirty with dust and the rust-tainted surfaces of water tanks, proving the robot's performance in a real environment. It was experimentally demonstrated that the robot not only exhibited high speed, but also can switch from floor to wall and from wall to ceiling, and overcome 5-cm high obstacles protruding from walls without difficulty.
The new climbing quadrupedal robot is expected to be widely used for inspection, repair, and maintenance of large steel structures such as ships, bridges, transmission towers, oil pipelines, large storage areas, and construction sites. As the works required in these places involves risks such as falls, suffocation and other accidents that may result in serious injuries or casualties, the need for automation is of utmost urgency.
One of the first co-authors of the paper, a Ph.D. student, Yong Um of KAIST’s Department of Mechanical Engineering, said, "By the use of the magnetic soles made up of the EPM and MRE and the non-linear model predictive controller suitable for climbing, the robot can speedily move through a variety of ferromagnetic surfaces including walls and ceilings, not just level grounds. We believe this would become a cornerstone that will expand the mobility and the places of pedal-mobile robots can venture into." He added, “These robots can be put into good use in executing dangerous and difficult tasks on steel structures in places like the shipbuilding yards.”
This research was carried out with support from the National Research Foundation of Korea's Basic Research in Science & Engineering Program for Mid-Career Researchers and Korea Shipbuilding & Offshore Engineering Co., Ltd..
< Figure 1. The quadrupedal robot (MARVEL) walking over various ferrous surfaces. (A) vertical wall (B) ceiling. (C) over obstacles on a vertical wall (D) making floor-to-wall and wall-to-ceiling transitions (E) moving over a storage tank (F) walking on a wall with a 2-kg weight and over a ceiling with a 3-kg load. >
< Figure 2. Description of the magnetic foot (A) Components of the magnet sole: ankle, Square Eletro-Permanent Magnet(S-EPM), MRE footpad. (B) Components of the S-EPM and MRE footpad. (C) Working principle of the S-EPM. When the magnetization direction is aligned as shown in the left figure, magnetic flux comes out of the keeper and circulates through the steel plate, generating holding force (ON state). Conversely, if the magnetization direction is aligned as shown in the figure on the right, the magnetic flux circulates inside the S-EPM and the holding force disappears (OFF state). >
Video Introduction: Agile and versatile climbing on ferromagnetic surfaces with a quadrupedal robot - YouTube
2022.12.30 View 12438 -
Tomographic Measurement of Dielectric Tensors
Dielectric tensor tomography allows the direct measurement of the 3D dielectric tensors of optically anisotropic structures
A research team reported the direct measurement of dielectric tensors of anisotropic structures including the spatial variations of principal refractive indices and directors. The group also demonstrated quantitative tomographic measurements of various nematic liquid-crystal structures and their fast 3D nonequilibrium dynamics using a 3D label-free tomographic method. The method was described in Nature Materials.
Light-matter interactions are described by the dielectric tensor. Despite their importance in basic science and applications, it has not been possible to measure 3D dielectric tensors directly. The main challenge was due to the vectorial nature of light scattering from a 3D anisotropic structure. Previous approaches only addressed 3D anisotropic information indirectly and were limited to two-dimensional, qualitative, strict sample conditions or assumptions.
The research team developed a method enabling the tomographic reconstruction of 3D dielectric tensors without any preparation or assumptions. A sample is illuminated with a laser beam with various angles and circularly polarization states. Then, the light fields scattered from a sample are holographically measured and converted into vectorial diffraction components. Finally, by inversely solving a vectorial wave equation, the 3D dielectric tensor is reconstructed.
Professor YongKeun Park said, “There were a greater number of unknowns in direct measuring than with the conventional approach. We applied our approach to measure additional holographic images by slightly tilting the incident angle.”
He said that the slightly tilted illumination provides an additional orthogonal polarization, which makes the underdetermined problem become the determined problem. “Although scattered fields are dependent on the illumination angle, the Fourier differentiation theorem enables the extraction of the same dielectric tensor for the slightly tilted illumination,” Professor Park added.
His team’s method was validated by reconstructing well-known liquid crystal (LC) structures, including the twisted nematic, hybrid aligned nematic, radial, and bipolar configurations. Furthermore, the research team demonstrated the experimental measurements of the non-equilibrium dynamics of annihilating, nucleating, and merging LC droplets, and the LC polymer network with repeating 3D topological defects.
“This is the first experimental measurement of non-equilibrium dynamics and 3D topological defects in LC structures in a label-free manner. Our method enables the exploration of inaccessible nematic structures and interactions in non-equilibrium dynamics,” first author Dr. Seungwoo Shin explained.
-PublicationSeungwoo Shin, Jonghee Eun, Sang Seok Lee, Changjae Lee, Herve Hugonnet, Dong Ki Yoon, Shin-Hyun Kim, Jongwoo Jeong, YongKeun Park, “Tomographic Measurement ofDielectric Tensors at Optical Frequency,” Nature Materials March 02, 2022 (https://doi.org/10/1038/s41563-022-01202-8)
-ProfileProfessor YongKeun ParkBiomedical Optics Laboratory (http://bmol.kaist.ac.kr)Department of PhysicsCollege of Natural SciencesKAIST
2022.03.22 View 6148 -
Label-Free Multiplexed Microtomography of Endogenous Subcellular Dynamics Using Deep Learning
AI-based holographic microscopy allows molecular imaging without introducing exogenous labeling agents
A research team upgraded the 3D microtomography observing dynamics of label-free live cells in multiplexed fluorescence imaging. The AI-powered 3D holotomographic microscopy extracts various molecular information from live unlabeled biological cells in real time without exogenous labeling or staining agents.
Professor YongKeum Park’s team and the startup Tomocube encoded 3D refractive index tomograms using the refractive index as a means of measurement. Then they decoded the information with a deep learning-based model that infers multiple 3D fluorescence tomograms from the refractive index measurements of the corresponding subcellular targets, thereby achieving multiplexed micro tomography. This study was reported in Nature Cell Biology online on December 7, 2021.
Fluorescence microscopy is the most widely used optical microscopy technique due to its high biochemical specificity. However, it needs to genetically manipulate or to stain cells with fluorescent labels in order to express fluorescent proteins. These labeling processes inevitably affect the intrinsic physiology of cells. It also has challenges in long-term measuring due to photobleaching and phototoxicity. The overlapped spectra of multiplexed fluorescence signals also hinder the viewing of various structures at the same time. More critically, it took several hours to observe the cells after preparing them.
3D holographic microscopy, also known as holotomography, is providing new ways to quantitatively image live cells without pretreatments such as staining. Holotomography can accurately and quickly measure the morphological and structural information of cells, but only provides limited biochemical and molecular information.
The 'AI microscope' created in this process takes advantage of the features of both holographic microscopy and fluorescence microscopy. That is, a specific image from a fluorescence microscope can be obtained without a fluorescent label. Therefore, the microscope can observe many types of cellular structures in their natural state in 3D and at the same time as fast as one millisecond, and long-term measurements over several days are also possible.
The Tomocube-KAIST team showed that fluorescence images can be directly and precisely predicted from holotomographic images in various cells and conditions. Using the quantitative relationship between the spatial distribution of the refractive index found by AI and the major structures in cells, it was possible to decipher the spatial distribution of the refractive index. And surprisingly, it confirmed that this relationship is constant regardless of cell type.
Professor Park said, “We were able to develop a new concept microscope that combines the advantages of several microscopes with the multidisciplinary research of AI, optics, and biology. It will be immediately applicable for new types of cells not included in the existing data and is expected to be widely applicable for various biological and medical research.”
When comparing the molecular image information extracted by AI with the molecular image information physically obtained by fluorescence staining in 3D space, it showed a 97% or more conformity, which is a level that is difficult to distinguish with the naked eye.
“Compared to the sub-60% accuracy of the fluorescence information extracted from the model developed by the Google AI team, it showed significantly higher performance,” Professor Park added.
This work was supported by the KAIST Up program, the BK21+ program, Tomocube, the National Research Foundation of Korea, and the Ministry of Science and ICT, and the Ministry of Health & Welfare.
-Publication
Hyun-seok Min, Won-Do Heo, YongKeun Park, et al. “Label-free multiplexed microtomography of endogenous subcellular dynamics using generalizable deep learning,” Nature Cell Biology (doi.org/10.1038/s41556-021-00802-x) published online December 07 2021.
-Profile
Professor YongKeun Park
Biomedical Optics Laboratory
Department of Physics
KAIST
2022.02.09 View 8086 -
Flexible Sensor-Integrated RFA Needle Leads to Smarter Medical Treatment
Clinical trial of flexible sensor-integrated radiofrequency ablation (RFA) needle tip monitors physical changes and steam pop
Researchers have designed a thin polymeric sensor platform on a radiofrequency ablation needle to monitor temperature and pressure in real time. The sensors integrated onto 1.5 mm diameter needle tip have proven their efficacy during clinical tests and expect to provide a new opportunity for safer and more effective medical practices. The research was reported in Advanced Science as the frontispiece on August 5.
Radiofrequency ablation (RFA) is a minimally invasive surgery technique for removing tumors and treating cardiovascular disease. During a procedure, an unintended audible explosion called ‘steam pop’ can occur due to the increased internal steam pressure in the ablation region. This phenomenon has been cited as a cause of various negative thermal and mechanical effects on neighboring tissue. Even more, the relationship between steam pop and cancer recurrence is still being investigated.
Professor Inkyu Park said that his team’s integrated sensors reliably detected the occurrence of steam pop. The sensors also monitor rapidly spreading hot steam in tissue. It is expected that the diverse properties of tissue undergoing RFA could be checked by utilizing the physical sensors integrated on the needle.
“We believe that the integrated sensors can provide useful information about a variety of medical procedures and accompanying environmental changes in the human body, and help develop more effective and safer surgical procedures,” said Professor Park.
Professor Park’s team built a thin film type pressure and temperature sensor stack with a thickness of less than 10 μm using a microfabrication process. For the pressure sensor, the team used contact resistance changes between metal electrodes and a carbon nanotube coated polymeric membrane. The entire sensor array was thoroughly insulated with medical tubes to minimize any exposure of the sensor materials to external tissue and maximize its biocompatibility.
During the clinical trial, the research team found that the accumulated hot steam is suddenly released during steam pops and this hot air spreads to neighboring tissue, which accelerates the ablation process. Furthermore, using in-situ ultrasound imaging and computational simulations, the research team could confirm the non-uniform temperature distribution around the RFA needle can be one of the primary reasons for the steam popping.
Professor Park explained that various physical and chemical sensors for different targets can be added to create other medical devices and industrial tools.
“This result will expand the usability and applicability of current flexible sensor technologies. We are also trying to integrate this sensor onto a 0.3mm diameter needle for in-vivo diagnosis applications and expect that this approach can be applied to other medical treatments as well as the industrial field,” added Professor Park. This study was supported by the National Research Foundation of Korea.
-PublicationJaeho Park, Jinwoo Lee, Hyo Keun Lim, Inkyu Park et al. “Real-Time Internal Steam Pop Detection during Radiofrequency Ablation with a Radiofrequency Ablation Needle Integrated with a Temperature and Pressure Sensor: Preclinical and clinical pilot tests," Advanced Science (https://doi/org/10.1002/advs.202100725) on August 5, 2021
-ProfileProfessor Inkyu ParkMicro & Nano Tranducers Laboratory http://mintlab1.kaist.ac.kr/
Department of Mechanical EngineeringCollege of EngineeringKAIST
2021.10.20 View 6750 -
A Study Reveals What Triggers Lung Damage during COVID-19
A longitudinal study of macrophages from SARS-CoV-2 infected lungs offers new insights into dynamic immunological changes
A KAIST immunology research team found that a specific subtype of macrophages that originated from blood monocytes plays a key role in the hyper-inflammatory response in SARS-CoV-2 infected lungs, by performing single-cell RNA sequencing of bronchoalveolar lavage fluid cells. This study provides new insights for understanding dynamic changes in immune responses to COVID-19.
In the early phase of COVID-19, SARS-CoV-2 infected lung tissue and the immediate defense system is activated. This early and fast response is called ‘innate immunity,’ provided by immune cells residing in lungs. Macrophages are major cell types of the innate immune system of the lungs, and newly differentiated macrophages originating from the bloodstream also contribute to early defenses against viruses.
Professor Su-Hyung Park and his collaborators investigated the quantitative and qualitative evaluation of immune responses in the lungs of SARS-CoV-2 infected ferrets. To overcome the limitations of research using patient-originated specimens, the researchers used a ferret infection model to obtain SARS-CoV-2 infected lungs sequentially with a defined time interval.
The researchers analyzed the 10 subtypes of macrophages during the five-day course of SARS-CoV-2 infection, and found that infiltrating macrophages originating from activated monocytes in the blood were key players for viral clearance as well as damaged lung tissue. Moreover, they found that the differentiation process of these inflammatory macrophages resembled the immune responses in the lung tissue of severe COVID-19 patients.
Currently, the research team is conducting a follow-up study to identify the dynamic changes in immune responses during the use of immunosuppressive agents to control hyper-inflammatory response called ‘cytokine storm’ in patients with COVID-19.
Dr. Jeong Seok Lee, the chief medical officer at Genome Insight Inc., explained, “Our analysis will enhance the understanding of the early features of COVID-19 immunity and provide a scientific background for the more precise use of immunosuppressive agents targeting specific macrophage subtypes.”
“This study is the first longitudinal study using sequentially obtained immune cells originating from SARS-CoV-2 infected lungs. The research describes the innate immune response to COVID-19 using single cell transcriptome data and enhances our understanding of the two phases of inflammatory responses,” Professor Park said.
This work was supported by the Ministry of Health and Welfare and KAIST, and was published in Nature Communications on July 28.
-PublicationSu-Hyung Park, Jeong Seok Lee, Su-Hyung Park et al. “Single-cell transcriptome of bronchoalverolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets” Nature Communications (https://doi.org/10.1038/s41467-021-24807-0)
-ProfileProfessor Su-Hyung ParkLaboratory of Translational Immunology and Vaccinologyhttps://ltiv.kaist.ac.kr/
Graduate School of Medical Science and EngineeringKAIST
2021.08.04 View 10816 -
Hydrogel-Based Flexible Brain-Machine Interface
The interface is easy to insert into the body when dry, but behaves ‘stealthily’ inside the brain when wet
Professor Seongjun Park’s research team and collaborators revealed a newly developed hydrogel-based flexible brain-machine interface. To study the structure of the brain or to identify and treat neurological diseases, it is crucial to develop an interface that can stimulate the brain and detect its signals in real time. However, existing neural interfaces are mechanically and chemically different from real brain tissue. This causes foreign body response and forms an insulating layer (glial scar) around the interface, which shortens its lifespan.
To solve this problem, the research team developed a ‘brain-mimicking interface’ by inserting a custom-made multifunctional fiber bundle into the hydrogel body. The device is composed not only of an optical fiber that controls specific nerve cells with light in order to perform optogenetic procedures, but it also has an electrode bundle to read brain signals and a microfluidic channel to deliver drugs to the brain.
The interface is easy to insert into the body when dry, as hydrogels become solid. But once in the body, the hydrogel will quickly absorb body fluids and resemble the properties of its surrounding tissues, thereby minimizing foreign body response.
The research team applied the device on animal models, and showed that it was possible to detect neural signals for up to six months, which is far beyond what had been previously recorded. It was also possible to conduct long-term optogenetic and behavioral experiments on freely moving mice with a significant reduction in foreign body responses such as glial and immunological activation compared to existing devices.
“This research is significant in that it was the first to utilize a hydrogel as part of a multifunctional neural interface probe, which increased its lifespan dramatically,” said Professor Park. “With our discovery, we look forward to advancements in research on neurological disorders like Alzheimer’s or Parkinson’s disease that require long-term observation.”
The research was published in Nature Communications on June 8, 2021. (Title: Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity) The study was conducted jointly with an MIT research team composed of Professor Polina Anikeeva, Professor Xuanhe Zhao, and Dr. Hyunwoo Yook.
This research was supported by the National Research Foundation (NRF) grant for emerging research, Korea Medical Device Development Fund, KK-JRC Smart Project, KAIST Global Initiative Program, and Post-AI Project.
-PublicationPark, S., Yuk, H., Zhao, R. et al. Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity. Nat Commun 12, 3435 (2021). https://doi.org/10.1038/s41467-021-23802-9
-ProfileProfessor Seongjun ParkBio and Neural Interfaces LaboratoryDepartment of Bio and Brain EngineeringKAIST
2021.07.13 View 9301