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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 883 -
KAIST Develops Stretchable Displays Featuring 25% Expansion Without Image Distortion
Stretchable displays, praised for their spatial efficiency, design flexibility, and human-like flexibility, are seen as the next generation of display technology. A team of Korean researchers has developed a stretchable display that can expand by 25% while maintaining clear image quality without distortion. It can also stretch and contract up to 5,000 times at 15% expansion without any performance degradation, making it the first deformation-free stretchable display with a negative Poisson's ratio* developed in Korea.
*Poisson’s ratio of -1: A ratio where both width and length stretch equally, expressed as a negative value. A positive Poisson's ratio represents the ratio where horizontal stretching leads to vertical contraction, which is the case for most materials.
KAIST (represented by President Kwang-Hyung Lee) announced on the 20th of August that a research team led by Professor Byeong-Soo Bae of the Department of Materials Science and Engineering (Director of the Wearable Platform Materials Technology Center) , in collaboration with the Korea Institute of Machinery & Materials (President Seoghyeon Ryu), successfully developed a stretchable display substrate that suppresses image distortion through omnidirectional stretchability.
Currently, most stretchable displays are made with highly elastic elastomer* materials, but these materials possess a positive Poisson's ratio, causing unavoidable image distortion when the display is stretched.
*Elastomer: A polymer with elasticity similar to rubber.
To address this, the introduction of auxetic* meta-structures has been gaining attention. Unlike conventional materials, auxetic structures have a unique 'negative Poisson's ratio,' expanding in all directions when stretched in just one direction. However, traditional auxetic structures contain many empty spaces, limiting their stability and usability in display substrates.
*Auxetic structure: A special geometric structure that exhibits a negative Poisson's ratio.
To tackle the issue of image distortion, Professor Bae's research team developed a method to create a seamless surface for the auxetic meta-structure, achieving the ideal negative Poisson's ratio of -1 and overcoming the biggest challenge in auxetic meta-structures.
To overcome the second issue of elastic modulus*, the team inserted a textile made of glass fiber bundles with a diameter of just 25 micrometers (a quarter of the thickness of human hair) into the elastomer material. They then filled the empty spaces with the same elastomer, creating a flat and stable integrated film without gaps.
*Elastic Modulus: The ratio that indicates the extent of deformation when force is applied to a material. A higher elastic modulus means that the material is less likely to deform under force.
The research team theoretically identified that the difference in elasticity between the auxetic structure and the elastomer material directly influences the negative Poisson's ratio and successfully achieved an elasticity difference of over 230,000 times, producing a film with a Poisson's ratio of -1, the theoretical limit.
< Figure 2. Deformation of S-AUX film. a) Configurations and visualized principal strain distribution of the optimized S-AUX film at various strain rates. b) Biaxial stretching image. While pristine elastomer shrinks in the directions that were not stretched, S-AUX film developed in this study expands in all directions simultaneously while maintaining its original shape. >
Professor Byeong-Soo Bae, who led the study, explained, "Preventing image distortion using auxetic structures in stretchable displays is a core technology, but it has faced challenges due to the many empty spaces in the surface, making it difficult to use as a substrate. This research outcome is expected to significantly accelerate commercialization through high-resolution, distortion-free stretchable display applications that utilize the entire surface."
This study, co-authored by Dr. Yung Lee from KAIST’s Department of Materials Science and Engineering and Dr. Bongkyun Jang from the Korea Institute of Machinery & Materials, was published on August 20th in the international journal Nature Communications under the title "A seamless auxetic substrate with a negative Poisson's ratio of –1".
The research was supported by the Wearable Platform Materials Technology Center at KAIST, the Korea Institute of Machinery & Materials, and LG Display.
< Figure 3. Structural configuration of the distortion-free display components on the S-AUX film and a contour image of a micro-LED chip transferred onto the S-AUX film. >
< Figure 4. Schematic illustrations and photographic images of the S-AUX film-based image: distortion-free display in its stretched state and released state. >
2024.09.20 View 2116 -
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 1535 -
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 4274 -
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 4781 -
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 6155 -
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.
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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 8095 -
Deep-Learning and 3D Holographic Microscopy Beats Scientists at Analyzing Cancer Immunotherapy
Live tracking and analyzing of the dynamics of chimeric antigen receptor (CAR) T-cells targeting cancer cells can open new avenues for the development of cancer immunotherapy. However, imaging via conventional microscopy approaches can result in cellular damage, and assessments of cell-to-cell interactions are extremely difficult and labor-intensive. When researchers applied deep learning and 3D holographic microscopy to the task, however, they not only avoided these difficultues but found that AI was better at it than humans were.
Artificial intelligence (AI) is helping researchers decipher images from a new holographic microscopy technique needed to investigate a key process in cancer immunotherapy “live” as it takes place. The AI transformed work that, if performed manually by scientists, would otherwise be incredibly labor-intensive and time-consuming into one that is not only effortless but done better than they could have done it themselves. The research, conducted by the team of Professor YongKeun Park from the Department of Physics, appeared in the journal eLife last December.
A critical stage in the development of the human immune system’s ability to respond not just generally to any invader (such as pathogens or cancer cells) but specifically to that particular type of invader and remember it should it attempt to invade again is the formation of a junction between an immune cell called a T-cell and a cell that presents the antigen, or part of the invader that is causing the problem, to it. This process is like when a picture of a suspect is sent to a police car so that the officers can recognize the criminal they are trying to track down. The junction between the two cells, called the immunological synapse, or IS, is the key process in teaching the immune system how to recognize a specific type of invader.
Since the formation of the IS junction is such a critical step for the initiation of an antigen-specific immune response, various techniques allowing researchers to observe the process as it happens have been used to study its dynamics. Most of these live imaging techniques rely on fluorescence microscopy, where genetic tweaking causes part of a protein from a cell to fluoresce, in turn allowing the subject to be tracked via fluorescence rather than via the reflected light used in many conventional microscopy techniques.
However, fluorescence-based imaging can suffer from effects such as photo-bleaching and photo-toxicity, preventing the assessment of dynamic changes in the IS junction process over the long term. Fluorescence-based imaging still involves illumination, whereupon the fluorophores (chemical compounds that cause the fluorescence) emit light of a different color. Photo-bleaching or photo-toxicity occur when the subject is exposed to too much illumination, resulting in chemical alteration or cellular damage.
One recent option that does away with fluorescent labelling and thereby avoids such problems is 3D holographic microscopy or holotomography (HT). In this technique, the refractive index (the way that light changes direction when encountering a substance with a different density—why a straw looks like it bends in a glass of water) is recorded in 3D as a hologram.
Until now, HT has been used to study single cells, but never cell-cell interactions involved in immune responses. One of the main reasons is the difficulty of “segmentation,” or distinguishing the different parts of a cell and thus distinguishing between the interacting cells; in other words, deciphering which part belongs to which cell.
Manual segmentation, or marking out the different parts manually, is one option, but it is difficult and time-consuming, especially in three dimensions. To overcome this problem, automatic segmentation has been developed in which simple computer algorithms perform the identification.
“But these basic algorithms often make mistakes,” explained Professor YongKeun Park, “particularly with respect to adjoining segmentation, which of course is exactly what is occurring here in the immune response we’re most interested in.”
So, the researchers applied a deep learning framework to the HT segmentation problem. Deep learning is a type of machine learning in which artificial neural networks based on the human brain recognize patterns in a way that is similar to how humans do this. Regular machine learning requires data as an input that has already been labelled. The AI “learns” by understanding the labeled data and then recognizes the concept that has been labelled when it is fed novel data. For example, AI trained on a thousand images of cats labelled “cat” should be able to recognize a cat the next time it encounters an image with a cat in it. Deep learning involves multiple layers of artificial neural networks attacking much larger, but unlabeled datasets, in which the AI develops its own ‘labels’ for concepts it encounters.
In essence, the deep learning framework that KAIST researchers developed, called DeepIS, came up with its own concepts by which it distinguishes the different parts of the IS junction process. To validate this method, the research team applied it to the dynamics of a particular IS junction formed between chimeric antigen receptor (CAR) T-cells and target cancer cells. They then compared the results to what they would normally have done: the laborious process of performing the segmentation manually. They found not only that DeepIS was able to define areas within the IS with high accuracy, but that the technique was even able to capture information about the total distribution of proteins within the IS that may not have been easily measured using conventional techniques.
“In addition to allowing us to avoid the drudgery of manual segmentation and the problems of photo-bleaching and photo-toxicity, we found that the AI actually did a better job,” Professor Park added.
The next step will be to combine the technique with methods of measuring how much physical force is applied by different parts of the IS junction, such as holographic optical tweezers or traction force microscopy.
-Profile
Professor YongKeun Park
Department of Physics
Biomedical Optics Laboratory
http://bmol.kaist.ac.kr
KAIST
2021.02.24 View 10322 -
Extremely Stable Perovskite Nanoparticles Films for Next-Generation Displays
Researchers have reported an extremely stable cross-linked perovskite nanoparticle that maintains a high photoluminescence quantum yield (PLQY) for 1.5 years in air and harsh liquid environments. This stable material’s design strategies, which addressed one of the most critical problems limiting their practical application, provide a breakthrough for the commercialization of perovskite nanoparticles in next-generation displays and bio-related applications.
According to the research team led by Professor Byeong-Soo Bae, their development can survive in severe environments such as water, various polar solvents, and high temperature with high humidity without additional encapsulation. This development is expected to enable perovskite nanoparticles to be applied to high color purity display applications as a practical color converting material. This result was published as the inside front cover article in Advanced Materials.
Perovskites, which consist of organics, metals, and halogen elements, have emerged as key elements in various optoelectronic applications. The power conversion efficiency of photovoltaic cells based on perovskites light absorbers has been rapidly increased. Perovskites are also great promise as a light emitter in display applications because of their low material cost, facile wavelength tunability, high (PLQY), very narrow emission band width, and wider color gamut than inorganic semiconducting nanocrystals and organic emitters. Thanks to these advantages, perovskites have been identified as a key color-converting material for next-generation high color-purity displays. In particular, perovskites are the only luminescence material that meets Rec. 2020 which is a new color standard in display industry.
However, perovskites are very unstable against heat, moisture, and light, which makes them almost impossible to use in practical applications. To solve these problems, many researchers have attempted to physically prevent perovskites from coming into contact with water molecules by passivating the perovskite grain and nanoparticle surfaces with organic ligands or inorganic shell materials, or by fabricating perovskite-polymer nanocomposites. These methods require complex processes and have limited stability in ambient air and water. Furthermore, stable perovskite nanoparticles in the various chemical environments and high temperatures with high humidity have not been reported yet.
The research team in collaboration with Seoul National University develops siloxane-encapsulated perovskite nanoparticle composite films. Here, perovskite nanoparticles are chemically crosslinked with thermally stable siloxane molecules, thereby significantly improving the stability of the perovskite nanoparticles without the need for any additional protecting layer.
Siloxane-encapsulated perovskite nanoparticle composite films exhibited a high PLQY (> 70%) value, which can be maintained over 600 days in water, various chemicals (alcohol, strong acidic and basic solutions), and high temperatures with high humidity (85℃/85%). The research team investigated the mechanisms impacting the chemical crosslinking and water molecule-induced stabilization of perovskite nanoparticles through various photo-physical analysis and density-functional theory calculation.
The research team confirmed that displays based on their siloxane-perovskite nanoparticle composite films exhibited higher PLQY and a wider color gamut than those of Cd-based quantum dots and demonstrated perfect color converting properties on commercial mobile phone screens. Unlike what was commonly believed in the halide perovskite field, the composite films showed excellent bio-compatibility because the siloxane matrix prevents the toxicity of Pb in perovskite nanoparticle.
By using this technology, the instability of perovskite materials, which is the biggest challenge for practical applications, is greatly improved through simple encapsulation method.
“Perovskite nanoparticle is the only photoluminescent material that can meet the next generation display color standard. Nevertheless, there has been reluctant to commercialize it due to its moisture vulnerability. The newly developed siloxane encapsulation technology will trigger more research on perovskite nanoparticles as color conversion materials and will accelerate early commercialization,” Professor Bae said.
This work was supported by the Wearable Platform Materials Technology Center (WMC) of the Engineering Research Center (ERC) Project, and the Leadership Research Program funded by the National Research Foundation of Korea.
-Publication:
Junho Jang, Young-Hoon Kim, Sunjoon Park, Dongsuk Yoo, Hyunjin Cho, Jinhyeong Jang, Han Beom Jeong, Hyunhwan Lee, Jong Min Yuk, Chan Beum Park, Duk Young Jeon, Yong-Hyun Kim, Byeong-Soo Bae, and Tae-Woo Lee. “Extremely Stable Luminescent Crosslinked Perovskite Nanoparticles under Harsh Environments over 1.5 Years” Advanced Materials, 2020, 2005255. https://doi.org/10.1002/adma.202005255.
Link to download the full-text paper:
https://onlinelibrary.wiley.com/doi/10.1002/adma.202005255
-Profile: Prof. Byeong-Soo Bae (Corresponding author)
bsbae@kaist.ac.kr
Lab. of Optical Materials & Coating
Department of Materials Science and Engineering
Korea Advanced Institute of Science and Technology (KAIST)
2020.12.29 View 11008 -
Professor YongKeun Park Wins the 2018 Fumio Okano Award
(Professor Park)
Professor YongKeun Park from the Department of Physics won the 2018 Fumio Okano Award in recognition of his contributions to 3D display technology development during the annual conference of the International Society for Optics and Photonics (SPIE) held last month in Orlando, Florida in the US.
The Fumio Okano Best 3D Paper Prize is presented annually in memory of Dr. Fumio Okano, a pioneer and innovator of 3D displays who passed away in 2013, for his contributions to the field of 3D TVs and displays. The award is sponsored by NHK-ES.
Professor Park and his team are developing novel technology for measuring and visualizing 3D images by applying random light scattering. He has published numerous papers on 3D holographic camera technology and 3000x enhanced performance of 3D holographic displays in renowned international journals such as Nature Photonics, Nature Communications, and Science Advances. His technology has drawn international attention from renowned media outlets including Newsweek and Forbes.
He has established two startups to commercialize his technology. Tomocube specializes in 3D imaging microscopes using holotomographic technology and the company exports their products to several countries including the US and Japan. The.Wave.Talk is exploring technology for examining pre-existing bacteria anywhere and anytime.
Professor Park’s innovations have already been recognized in and out of KAIST. In February, he was selected as the KAISTian of the Year for his outstanding research, commercialization, and startups. He was also decorated with the National Science Award in April by the Ministry of Science and ICT and the Hong Jin-Ki Innovation Award later in May by the Yumin Cultural Foundation.
Professor Park said, “3D holography is emerging as a significant technology with growing potential and positive impacts on our daily lives. However, the current technology lags far behind the levels displayed in SF movies. We will do our utmost to reach this level with more commercialization."
2018.05.31 View 8956 -
Meet the KAISTian of 2017, Professor YongKeun Park
Professor YongKeun Park from the Department of Physics is one of the star professors in KAIST. Rising to the academic stardom, Professor Park’s daily schedule is filled with series of business meetings in addition to lab meetings and lectures.
The year 2017 must have been special for him. During the year, he published numerous papers in international journals, such as Nature Photonics, Nature Communications and Science Advances. These high performances drew international attention from renowned media, including Newsweek and Forbes. Moreover, recognizing his research performance, he was elected as a fellow member of the Optical Society (OSA) in his mid-30s. Noting that the members’ age ranges from late 50s to early 60s, Professor Park’s case considered to be quite exceptional.
Adding to his academic achievement, he has launched two startups powered of his own technologies. One is called Tomocube, a company specialized in 3-D imaging microscope using holotomography technology. His company is currently exporting the products to multiple countries, including the United States and Japan. The other one is The.Wave.Talk which has technologies for examining pre-existing bacteria anywhere and anytime.
His research career and entrepreneurship are well deserved recipient of many honors. At the 2018 kick-off ceremony, Professor Park was awarded the KAISTian of 2017 in recognition of his developing holographic measure and control technology as well as founding a new field for technology application.
KAISTian of the Year, first presented in 2001, is an award to recognize the achievements and exemplary contribution of KAIST member who has put significant effort nationally and internationally, enhancing the value of KAIST.
While receiving the award, he thanked his colleagues and his students who have achieved this far together. He said, “I would like to thank KAIST for providing environment for young professors like me so that we can engage themselves in research. Also, I would like to mention that I am an idea seeder and my students do the most of the research. So, I appreciate my students for their hard works, and it is very pleasure to have them. Lastly, I thank the professors for teaching these outstanding students. I feel great responsibility over this title. I will dedicate myself to make further progress in commercializing technology in KAIST.”
Expecting his successful startup cases as a model and great inspiration to students as well as professors, KAIST interviewed Professor Park.
Q What made you decide to found your startups?
A I believed that my research areas could be further used. As a professor, I believe that it is a university’s role to create added value through commercializing technology and creating startups.
Q You have co-founded two startups. What is your role in each company?
A So, basically I have two full-time jobs, professor in KAIST and CTO in Tomocube. After transferring the technology, I hold the position of advisor in The.Wave.Talk.
(Holographic images captured by the product Professor Park developed)
Q Do your students also participate in your companies or can they?
A No, the school and companies are separate spaces; in other words, they are not participating in my companies. They have trained my employees when transferring the technologies, but they are not directly working for the companies.
However, they can participate if they want to. If there’s a need to develop a certain technology, an industry-academia contract can be made. According to the agreement, students can work for the companies.
Q Were there any hardships when preparing the startups?
A At the initial stage, I did not have a financial problem, thanks to support from Startup KAIST. Yet, inviting capital is the beginning, and I think every step I made to operate, generate revenue, and so on is not easy.
Q Do you believe KAIST is startup-friendly?
A Yes, there’s no school like KAIST in Korea and any other country. Besides various programs to support startup activities, Startup KAIST has many professors equipped with a great deal of experience. Therefore, I believe that KAIST provides an excellent environment for both students and professors to create startups.
Q Do you have any suggestion to KAIST institutionally?
A Well, I would like to make a comment to students and professors in KAIST. I strongly recommend them to challenge themselves by launching startups if they have good ideas. Many students wish to begin their jobs in government-funded research institutes or major corporates, but I believe that engaging in a startup company will also give them valuable and very productive experience.
Unlike before, startup institutions are well established, so attracting good capital is not so hard. There are various activities offered by Startup KAIST, so it’s worthwhile giving it a try.
Q What is your goal for 2018 as a professor and entrepreneur?
A I don’t have a grand plan, but I will work harder to produce good students with new topics in KAIST while adding power to my companies to grow bigger.
By Se Yi Kim from the PR Office
2018.01.03 View 9885 -
Professor YongKeun Park Elected as a Fellow of the Optical Society
Professor YongKeun Park, from the Department of Physics at KAIST, was elected as a fellow member of the Optical Society (OSA) in Washington, D.C. on September 12. Fellow membership is given to members who have made a significant contribution to the advancement of optics and photonics.
Professor Park was recognized for his research on digital holography and wavefront control technology.
Professor Park has been producing outstanding research outcomes in the field of holographic technology and light scattering control since joining KAIST in 2010. In particular, he developed and commercialized technology for a holographic telescope. He applied it to various medical and biological research projects, leading the field worldwide.
In the past, cells needed to be dyed with fluorescent materials to capture a 3-D image. However, Professor Park’s holotomography (HT) technology can capture 3-D images of living cells and tissues in real time without color dyeing. This technology allows diversified research in the biological and medical field.
Professor Park established a company, Tomocube, Inc. in 2015 to commercialize the technology. In 2016, he received funding from SoftBank Ventures and Hanmi Pharmaceutical. Currently, major institutes, including MIT, the University of Pittsburgh, the German Cancer Research Center, and Seoul National University Hospital are using his equipment.
Recently, Professor Park and his team developed technology based on light scattering measurements. With this technology, they established a company called The Wave Talk and received funding from various organizations, such as NAVER. Its first product is about to be released.
Professor Park said, “I am glad to become a fellow member based on the research outcomes I produced since I was appointed as a professor at KAIST. I would like to thank the excellent researchers as well as the school for its support. I will devote myself to continuously producing novel outcomes in both basic and applied fields.”
Professor Park has published nearly 100 papers in renowned journals including Nature Photonics, Nature Communications, Science Advances, and Physical Review Letters.
2017.10.18 View 10159