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Deep-Learning and 3D Holographic Microscopy Beats Scientists at Analyzing Cancer Immunotherapy
Live tracking and analyzing of the dynamics of chimeric antigen receptor (CAR) T-cells targeting cancer cells can open new avenues for the development of cancer immunotherapy. However, imaging via conventional microscopy approaches can result in cellular damage, and assessments of cell-to-cell interactions are extremely difficult and labor-intensive. When researchers applied deep learning and 3D holographic microscopy to the task, however, they not only avoided these difficultues but found that AI was better at it than humans were.
Artificial intelligence (AI) is helping researchers decipher images from a new holographic microscopy technique needed to investigate a key process in cancer immunotherapy “live” as it takes place. The AI transformed work that, if performed manually by scientists, would otherwise be incredibly labor-intensive and time-consuming into one that is not only effortless but done better than they could have done it themselves. The research, conducted by the team of Professor YongKeun Park from the Department of Physics, appeared in the journal eLife last December.
A critical stage in the development of the human immune system’s ability to respond not just generally to any invader (such as pathogens or cancer cells) but specifically to that particular type of invader and remember it should it attempt to invade again is the formation of a junction between an immune cell called a T-cell and a cell that presents the antigen, or part of the invader that is causing the problem, to it. This process is like when a picture of a suspect is sent to a police car so that the officers can recognize the criminal they are trying to track down. The junction between the two cells, called the immunological synapse, or IS, is the key process in teaching the immune system how to recognize a specific type of invader.
Since the formation of the IS junction is such a critical step for the initiation of an antigen-specific immune response, various techniques allowing researchers to observe the process as it happens have been used to study its dynamics. Most of these live imaging techniques rely on fluorescence microscopy, where genetic tweaking causes part of a protein from a cell to fluoresce, in turn allowing the subject to be tracked via fluorescence rather than via the reflected light used in many conventional microscopy techniques.
However, fluorescence-based imaging can suffer from effects such as photo-bleaching and photo-toxicity, preventing the assessment of dynamic changes in the IS junction process over the long term. Fluorescence-based imaging still involves illumination, whereupon the fluorophores (chemical compounds that cause the fluorescence) emit light of a different color. Photo-bleaching or photo-toxicity occur when the subject is exposed to too much illumination, resulting in chemical alteration or cellular damage.
One recent option that does away with fluorescent labelling and thereby avoids such problems is 3D holographic microscopy or holotomography (HT). In this technique, the refractive index (the way that light changes direction when encountering a substance with a different density—why a straw looks like it bends in a glass of water) is recorded in 3D as a hologram.
Until now, HT has been used to study single cells, but never cell-cell interactions involved in immune responses. One of the main reasons is the difficulty of “segmentation,” or distinguishing the different parts of a cell and thus distinguishing between the interacting cells; in other words, deciphering which part belongs to which cell.
Manual segmentation, or marking out the different parts manually, is one option, but it is difficult and time-consuming, especially in three dimensions. To overcome this problem, automatic segmentation has been developed in which simple computer algorithms perform the identification.
“But these basic algorithms often make mistakes,” explained Professor YongKeun Park, “particularly with respect to adjoining segmentation, which of course is exactly what is occurring here in the immune response we’re most interested in.”
So, the researchers applied a deep learning framework to the HT segmentation problem. Deep learning is a type of machine learning in which artificial neural networks based on the human brain recognize patterns in a way that is similar to how humans do this. Regular machine learning requires data as an input that has already been labelled. The AI “learns” by understanding the labeled data and then recognizes the concept that has been labelled when it is fed novel data. For example, AI trained on a thousand images of cats labelled “cat” should be able to recognize a cat the next time it encounters an image with a cat in it. Deep learning involves multiple layers of artificial neural networks attacking much larger, but unlabeled datasets, in which the AI develops its own ‘labels’ for concepts it encounters.
In essence, the deep learning framework that KAIST researchers developed, called DeepIS, came up with its own concepts by which it distinguishes the different parts of the IS junction process. To validate this method, the research team applied it to the dynamics of a particular IS junction formed between chimeric antigen receptor (CAR) T-cells and target cancer cells. They then compared the results to what they would normally have done: the laborious process of performing the segmentation manually. They found not only that DeepIS was able to define areas within the IS with high accuracy, but that the technique was even able to capture information about the total distribution of proteins within the IS that may not have been easily measured using conventional techniques.
“In addition to allowing us to avoid the drudgery of manual segmentation and the problems of photo-bleaching and photo-toxicity, we found that the AI actually did a better job,” Professor Park added.
The next step will be to combine the technique with methods of measuring how much physical force is applied by different parts of the IS junction, such as holographic optical tweezers or traction force microscopy.
-Profile
Professor YongKeun Park
Department of Physics
Biomedical Optics Laboratory
http://bmol.kaist.ac.kr
KAIST
2021.02.24 View 10608 -
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 11258 -
Researchers Control Multiple Wavelengths of Light from a Single Source
KAIST researchers have synthesized a collection of nanoparticles, known as carbon dots, capable of emitting multiple wavelengths of light from a single particle. Additionally, the team discovered that the dispersion of the carbon dots, or the interparticle distance between each dot, influences the properties of the light the carbon dots emit. The discovery will allow researchers to understand how to control these carbon dots and create new, environmentally responsible displays, lighting, and sensing technology.
Research into nanoparticles capable of emitting light, such as quantum dots, has been an active area of interest for the last decade and a half. These particles, or phosphors, are nanoparticles made out of various materials that are capable of emitting light at specific wavelengths by leveraging quantum mechanical properties of the materials. This provides new ways to develop lighting and display solutions as well as more precise detection and sensing in instruments.
As technology becomes smaller and more sophisticated, the usage of fluorescent nanoparticles has seen a dramatic increase in many applications due to the purity of the colors emitting from the dots as well as their tunability to meet desired optical properties.
Carbon dots, a type of fluorescent nanoparticles, have seen an increase in interest from researchers as a candidate to replace non-carbon dots, the construction of which requires heavy metals that are toxic to the environment. Since they are made up of mostly carbon, the low toxicity is an extremely attractive quality when coupled with the tunability of their inherent optical properties.
Another striking feature of carbon dots is their capability to emit multiple wavelengths of light from a single nanoparticle. This multi-wavelength emission can be stimulated under a single excitation source, enabling the simple and robust generation of white light from a single particle by emitting multiple wavelengths simultaneously.
Carbon dots also exhibit a concentration-dependent photoluminescence. In other words, the distance between individual carbon dots affects the light that the carbon dots subsequently emit under an excitation source. These combined properties make carbon dots a unique source that will result in extremely accurate detection and sensing.
This concentration-dependency, however, had not been fully understood. In order to fully utilize the capabilities of carbon dots, the mechanisms that govern the seemingly variable optical properties must first be uncovered. It was previously theorized that the concentration-dependency of carbon dots was due to a hydrogen bonding effect.
Now, a KAIST research team, led by Professor Do Hyun Kim of the Department of Chemical and Biomolecular Engineering has posited and demonstrated that the dual-color-emissiveness is instead due to the interparticle distances between each carbon dot. This study was made available online in June 2020 ahead of final publication in the 36th Issue of Physical Chemistry Chemical Physics on September 28, 2020.
First author of the paper, PhD candidate Hyo Jeong Yoo, along with Professor Kim and researcher Byeong Eun Kwak, examined how the relative light intensity of the red and blue colors changed when varying the interparticle distances, or concentration, of the carbon dots. They found that as the concentration was adjusted, the light emitted from the carbon dots would transform. By varying the concentration, the team was able to control the relative intensity of the colors, as well as emit them simultaneously to generate a white light from a single source (See Figure).
“The concentration-dependence of the photoluminescence of carbon dots on the change of the emissive origins for different interparticle distances has been overlooked in previous research. With the analysis of the dual-color-emission phenomenon of carbon dots, we believe that this result may provide a new perspective to investigate their photoluminescence mechanism,” Yoo explained.
The newly analyzed ability to control the photoluminescence of carbon dots will likely be heavily utilized in the continued development of solid-state lighting applications and sensing.
Publication:
Yoo, H. J., Kwak, B. E., and Kim. D. H. (2020) Interparticle distance as a key factor for controlling the dual-emission properties of carbon dots. Physical Chemistry Chemical Physics, Issue 36, Pages 20227-20237. Available online at https://doi.org/10.1039/d0cp02120b
Profile:
Do Hyun Kim, Sc.D.
Professor
dokim@kaist.ac.kr
http://procal.kaist.ac.kr/
Process Analysis Laboratory
Department of Chemical and Biomolecular Engineering
https://www.kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)Daejeon, Republic of Korea
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2020.11.23 View 9458 -
‘WalkON Suit 4’ Releases Paraplegics from Wheelchairs
- KAIST Athletes in ‘WalkON Suit 4’ Dominated the Cybathlon 2020 Global Edition. -
Paraplegic athletes Byeong-Uk Kim and Joohyun Lee from KAIST’s Team Angel Robotics won a gold and a bronze medal respectively at the Cybathlon 2020 Global Edition last week. ‘WalkON Suit 4,’ a wearable robot developed by the Professor Kyoungchul Kong’s team from the Department of Mechanical Engineering topped the standings at the event with double medal success.
Kim, the former bronze medallist, clinched his gold medal by finishing all six tasks in 3 minutes and 47 seconds, whereas Lee came in third with a time of 5 minutes and 51 seconds. TWIICE, a Swiss team, lagged 53 seconds behind Kim’s winning time to be the runner-up.
Cybathlon is a global championship, organized by ETH Zurich, which brings together people with physical disabilities to compete using state-of-the-art assistive technologies to perform everyday tasks. The first championship was held in 2016 in Zurich, Switzerland.
Due to the COVID-19 pandemic, the second championship was postponed twice and held in a new format in a decentralized setting. A total of 51 teams from 20 countries across the world performed the events in their home bases in different time zones instead of traveling to Zurich. Under the supervision of a referee and timekeeper, all races were filmed and then reviewed by judges.
KAIST’s Team Angel Robotics participated in the Powered Exoskeleton Race category, where nine pilots representing five nations including Korea, Switzerland, the US, Russia, and France competed against each other.
The team installed their own arena and raced at the KAIST Main Campus in Daejeon according to the framework, tasks, and rules defined by the competition committee. The two paraplegic pilots were each equipped with exoskeletal devices, the WalkON Suit 4, and undertook six tasks related to daily activities.
The WalkON Suit 4 recorded the fastest walking speed for a complete paraplegic ever reported. For a continuous walk, it achieved a maximum speed of 40 meters per minute. This is comparable to the average walking pace of a non-disabled person, which is around two to four kilometers per hour.
The research team raised the functionality of the robot by adding technology that can observe the user’s level of anxiety and external factors like the state of the walking surface, so it can control itself intelligently. The assistive functions a robot should provide vary greatly with the environment, and the WalkON Suit 4 made it possible to analyze the pace of the user within 30 steps and provide a personally optimized walking pattern, enabling a high walking speed.
The six tasks that Kim and Lee had to complete were:1) sitting and standing back up, 2) navigating around obstacles while avoiding collisions, 3) stepping over obstacles on the ground, 4) going up and down stairs, 5) walking across a tilted path, and 6) climbing a steep slope, opening and closing a door, and descending a steep slope.
Points were given based on the accuracy of each completed task, and the final scores were calculated by adding all of the points that were gained in each attempt, which lasted 10 minutes. Each pilot was given three opportunities and used his/her highest score. Should pilots have the same final score, the pilot who completed the race in the shortest amount of time would win.
Kim said in his victory speech that he was so thrilled to see all his and fellow researchers’ years of hard work paying off. “This will be a good opportunity to show how outstanding Korean wearable robot technologies are,” he added.
Lee, who participated in the competition for the first time, said, “By showing that I can overcome my physical disabilities with robot technology, I’d like to send out a message of hope to everyone who is tired because of COVID-19”.
Professor Kong’s team collaborated in technology development and pilot training with their colleagues from Angel Robotics Co., Ltd., Severance Rehabilitation Hospital, Yeungnam University, Stalks, and the Institute of Rehabilitation Technology.
Footage from the competition is available at the Cybathlon’s official website.
(END)
2020.11.20 View 7911 -
Experts to Help Asia Navigate the Post-COVID-19 and 4IR Eras
Risk Quotient 2020, an international conference co-hosted by KAIST and the National University of Singapore (NUS), will bring together world-leading experts from academia and industry to help Asia navigate the post-COVID-19 and Fourth Industrial Revolution (4IR) eras.
The online conference will be held on October 29 from 10 a.m. Korean time under the theme “COVID-19 Pandemic and A Brave New World”. It will be streamed live on YouTube at https://www.youtube.com/c/KAISTofficial and https://www.youtube.com/user/NUScast.
The Korea Policy Center for the Fourth Industrial Revolution (KPC4IR) at KAIST organized this conference in collaboration with the Lloyd's Register Foundation Institute for the Public Understanding of Risk (IPUR) at NUS.
During the conference, global leaders will examine the socioeconomic impacts of the COVID-19 pandemic on areas including digital innovation, education, the workforce, and the economy. They will then highlight digital and 4IR technologies that could be utilized to effectively mitigate the risks and challenges associated with the pandemic, while harnessing the opportunities that these socioeconomic effects may present. Their discussions will mainly focus on the Asian region.
In his opening remarks, KAIST President Sung-Chul Shin will express his appreciation for the Asian populations’ greater trust in and compliance with their governments, which have given the continent a leg up against the coronavirus. He will then emphasize that by working together through the exchange of ideas and global collaboration, we will be able to shape ‘a brave new world’ to better humanity. Welcoming remarks by Prof. Sang Yup Lee (Dean, KAIST Institutes) and Prof. Tze Yun Leong (Director, AI Technology at AI Singapore) will follow.
For the keynote speech, Prof. Lan Xue (Dean, Schwarzman College, Tsinghua University) will share China’s response to COVID-19 and lessons for crisis management. Prof. Danny Quah (Dean, Lee Kuan Yew School of Public Policy, NUS) will present possible ways to overcome these difficult times. Dr. Kak-Soo Shin (Senior Advisor, Shin & Kim LLC, Former Ambassador to the State of Israel and Japan, and Former First and Second Vice Minister of the Ministry of Foreign Affairs of the Republic of Korea) will stress the importance of the international community’s solidarity to ensure peace, prosperity, and safety in this new era.
Panel Session I will address the impact of COVID-19 on digital innovation. Dr. Carol Soon (Senior Research Fellow, Institute of Policy Studies, NUS) will present her interpretation of recent technological developments as both opportunities for our society as a whole and challenges for vulnerable groups such as low-income families. Dr. Christopher SungWook Chang (Managing Director, Kakao Mobility) will show how changes in mobility usage patterns can be captured by Kakao Mobility’s big data analysis. He will illustrate how the data can be used to interpret citizen’s behaviors and how risks can be transformed into opportunities by utilizing technology. Mr. Steve Ledzian’s (Vice President, Chief Technology Officer, FireEye) talk will discuss the dangers caused by threat actors and other cyber risk implications of COVID-19. Dr. June Sung Park (Chairman, Korea Software Technology Association (KOSTA)) will share how COVID-19 has accelerated digital transformations across all industries and why software education should be reformed to improve Korea’s competitiveness.
Panel Session II will examine the impact on education and the workforce. Dr. Sang-Jin Ban (President, Korean Educational Development Institute (KEDI)) will explain Korea’s educational response to the pandemic and the concept of “blended learning” as a new paradigm, and present both positive and negative impacts of online education on students’ learning experiences. Prof. Reuben Ng (Professor, Lee Kuan Yew School of Public Policy, NUS) will present on graduate underemployment, which seems to have worsened during COVID-19. Dr. Michael Fung’s presentation (Deputy Chief Executive (Industry), SkillsFuture SG) will introduce the promotion of lifelong learning in Singapore through a new national initiative known as the ‘SkillsFuture Movement’. This movement serves as an example of a national response to disruptions in the job market and the pace of skills obsolescence triggered by AI and COVID-19.
Panel Session III will touch on technology leadership and Asia’s digital economy and society. Prof. Naubahar Sharif (Professor, Division of Social Science and Division of Public Policy, Hong Kong University of Science and Technology (HKUST)) will share his views on the potential of China in taking over global technological leadership based on its massive domestic market, its government support, and the globalization process. Prof. Yee Kuang Heng (Professor, Graduate School of Public Policy, University of Tokyo) will illustrate how different legal and political needs in China and Japan have shaped the ways technologies have been deployed in responding to COVID-19. Dr. Hayun Kang (Head, International Cooperation Research Division, Korea Information Society Development Institute (KISDI)) will explain Korea’s relative success containing the pandemic compared to other countries, and how policy leaders and institutions that embrace digital technologies in the pursuit of public welfare objectives can produce positive outcomes while minimizing the side effects.
Prof. Kyung Ryul Park (Graduate School of Science and Technology Policy, KAIST) will be hosting the entire conference, whereas Prof. Alice Hae Yun Oh (Director, MARS Artificial Intelligence Research Center, KAIST), Prof. Wonjoon Kim (Dean, Graduate School of Innovation and Technology Management, College of Business, KAIST), Prof. Youngsun Kwon (Dean, KAIST Academy), and Prof. Taejun Lee (Korea Development Institute (KDI) School of Public Policy and Management) are to chair discussions with the keynote speakers and panelists.
Closing remarks will be delivered by Prof. Chan Ghee Koh (Director, NUS IPUR), Prof. So Young Kim (Director, KAIST KPC4IR), and Prof. Joungho Kim (Director, KAIST Global Strategy Institute (GSI)).
“This conference is expected to serve as a springboard to help Asian countries recover from global crises such as the COVID-19 pandemic through active cooperation and joint engagement among scholars, experts, and policymakers,” according to Director So Young Kim.
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2020.10.22 View 12326 -
Scientist of October: Professor Jungwon Kim
Professor Jungwon Kim from the Department of Mechanical Engineering was selected as the ‘Scientist of the Month’ for October 2020 by the Ministry of Science and ICT and the National Research Foundation of Korea. Professor Kim was recognized for his contributions to expanding the horizons of the basics of precision engineering through his research on multifunctional ultrahigh-speed, high-resolution sensors. He received 10 million KRW in prize money.
Professor Kim was selected as the recipient of this award in celebration of “Measurement Day”, which commemorates October 26 as the day in which King Sejong the Great established a volume measurement system.
Professor Kim discovered that the time difference between the pulse of light created by a laser and the pulse of the current produced by a light-emitting diode was as small as 100 attoseconds (10-16 seconds). He then developed a unique multifunctional ultrahigh-speed, high-resolution Time-of-Flight (TOF) sensor that could take measurements of multiple points at the same time by sampling electric light. The sensor, with a measurement speed of 100 megahertz (100 million vibrations per second), a resolution of 180 picometers (1/5.5 billion meters), and a dynamic range of 150 decibels, overcame the limitations of both existing TOF techniques and laser interferometric techniques at the same time. The results of this research were published in Nature Photonics on February 10, 2020.
Professor Kim said, “I’d like to thank the graduate students who worked passionately with me, and KAIST for providing an environment in which I could fully focus on research. I am looking forward to the new and diverse applications in the field of machine manufacturing, such as studying the dynamic phenomena in microdevices, or taking ultraprecision measurement of shapes for advanced manufacturing.”
(END)
2020.10.15 View 9670 -
Sturdy Fabric-Based Piezoelectric Energy Harvester Takes Us One Step Closer to Wearable Electronics
KAIST researchers presented a highly flexible but sturdy wearable piezoelectric harvester using the simple and easy fabrication process of hot pressing and tape casting. This energy harvester, which has record high interfacial adhesion strength, will take us one step closer to being able to manufacture embedded wearable electronics.
A research team led by Professor Seungbum Hong said that the novelty of this result lies in its simplicity, applicability, durability, and its new characterization of wearable electronic devices.
Wearable devices are increasingly being used in a wide array of applications from small electronics to embedded devices such as sensors, actuators, displays, and energy harvesters.
Despite their many advantages, high costs and complex fabrication processes remained challenges for reaching commercialization. In addition, their durability was frequently questioned. To address these issues, Professor Hong’s team developed a new fabrication process and analysis technology for testing the mechanical properties of affordable wearable devices.
For this process, the research team used a hot pressing and tape casting procedure to connect the fabric structures of polyester and a polymer film. Hot pressing has usually been used when making batteries and fuel cells due to its high adhesiveness. Above all, the process takes only two to three minutes.
The newly developed fabrication process will enable the direct application of a device into general garments using hot pressing just as graphic patches can be attached to garments using a heat press.
In particular, when the polymer film is hot pressed onto a fabric below its crystallization temperature, it transforms into an amorphous state. In this state, it compactly attaches to the concave surface of the fabric and infiltrates into the gaps between the transverse wefts and longitudinal warps. These features result in high interfacial adhesion strength. For this reason, hot pressing has the potential to reduce the cost of fabrication through the direct application of fabric-based wearable devices to common garments.
In addition to the conventional durability test of bending cycles, the newly introduced surface and interfacial cutting analysis system proved the high mechanical durability of the fabric-based wearable device by measuring the high interfacial adhesion strength between the fabric and the polymer film. Professor Hong said the study lays a new foundation for the manufacturing process and analysis of wearable devices using fabrics and polymers.
He added that his team first used the surface and interfacial cutting analysis system (SAICAS) in the field of wearable electronics to test the mechanical properties of polymer-based wearable devices. Their surface and interfacial cutting analysis system is more precise than conventional methods (peel test, tape test, and microstretch test) because it qualitatively and quantitatively measures the adhesion strength.
Professor Hong explained, “This study could enable the commercialization of highly durable wearable devices based on the analysis of their interfacial adhesion strength. Our study lays a new foundation for the manufacturing process and analysis of other devices using fabrics and polymers. We look forward to fabric-based wearable electronics hitting the market very soon.”
The results of this study were registered as a domestic patent in Korea last year, and published in Nano Energy this month. This study has been conducted through collaboration with Professor Yong Min Lee in the Department of Energy Science and Engineering at DGIST, Professor Kwangsoo No in the Department of Materials Science and Engineering at KAIST, and Professor Seunghwa Ryu in the Department of Mechanical Engineering at KAIST.
This study was supported by the High-Risk High-Return Project and the Global Singularity Research Project at KAIST, the National Research Foundation, and the Ministry of Science and ICT in Korea.
-Publication:
Jaegyu Kim, Seoungwoo Byun, Sangryun Lee, Jeongjae Ryu, Seongwoo Cho, Chungik Oh, Hongjun Kim, Kwangsoo No, Seunghwa Ryu, Yong Min Lee, Seungbum Hong*, Nano Energy 75 (2020), 104992.
https://doi.org/10.1016/j.nanoen.2020.104992
-Profile: Professor Seungbum Hong
seungbum@kaist.ac.kr
http://mii.kaist.ac.kr/
Department of Materials Science and Engineering
KAIST
2020.09.17 View 12142 -
Atomic Force Microscopy Reveals Nanoscale Dental Erosion from Beverages
KAIST researchers used atomic force microscopy to quantitatively evaluate how acidic and sugary drinks affect human tooth enamel at the nanoscale level. This novel approach is useful for measuring mechanical and morphological changes that occur over time during enamel erosion induced by beverages.
Enamel is the hard-white substance that forms the outer part of a tooth. It is the hardest substance in the human body, even stronger than bone. Its resilient surface is 96 percent mineral, the highest percentage of any body tissue, making it durable and damage-resistant. The enamel acts as a barrier to protect the soft inner layers of the tooth, but can become susceptible to degradation by acids and sugars.
Enamel erosion occurs when the tooth enamel is overexposed to excessive consumption of acidic and sugary food and drinks. The loss of enamel, if left untreated, can lead to various tooth conditions including stains, fractures, sensitivity, and translucence. Once tooth enamel is damaged, it cannot be brought back. Therefore, thorough studies on how enamel erosion starts and develops, especially at the initial stages, are of high scientific and clinical relevance for dental health maintenance.
A research team led by Professor Seungbum Hong from the Department of Materials Science and Engineering at KAIST reported a new method of applying atomic force microscopy (AFM) techniques to study the nanoscale characterization of this early stage of enamel erosion. This study was introduced in the Journal of the Mechanical Behavior of Biomedical Materials (JMBBM) on June 29.
AFM is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer (nm) that is equal to one billionth of a meter. AFM generates images by scanning a small cantilever over the surface of a sample, and this can precisely measure the structure and mechanical properties of the sample, such as surface roughness and elastic modulus.
The co-lead authors of the study, Dr. Panpan Li and Dr. Chungik Oh, chose three commercially available popular beverages, Coca-Cola®, Sprite®, and Minute Maid® orange juice, and immersed tooth enamel in these drinks over time to analyze their impacts on human teeth and monitor the etching process on tooth enamel.
Five healthy human molars were obtained from volunteers between age 20 and 35 who visited the KAIST Clinic. After extraction, the teeth were preserved in distilled water before the experiment. The drinks were purchased and opened right before the immersion experiment, and the team utilized AFM to measure the surface topography and elastic modulus map.
The researchers observed that the surface roughness of the tooth enamel increased significantly as the immersion time increased, while the elastic modulus of the enamel surface decreased drastically. It was demonstrated that the enamel surface roughened five times more when it was immersed in beverages for 10 minutes, and that the elastic modulus of tooth enamel was five times lower after five minutes in the drinks.
Additionally, the research team found preferential etching in scratched tooth enamel. Brushing your teeth too hard and toothpastes with polishing particles that are advertised to remove dental biofilms can cause scratches on the enamel surface, which can be preferential sites for etching, the study revealed.
Professor Hong said, “Our study shows that AFM is a suitable technique to characterize variations in the morphology and mechanical properties of dental erosion quantitatively at the nanoscale level.”
This work was supported by the National Research Foundation (NRF), the Ministry of Science and ICT (MSIT), and the KUSTAR-KAIST Institute of Korea.
A dentist at the KAIST Clinic, Dr. Suebean Cho, Dr. Sangmin Shin from the Smile Well Dental, and Professor Kack-Kyun Kim at the Seoul National University School of Dentistry also collaborated in this project.
Publication:
Li, P., et al. (2020) ‘Nanoscale effects of beverages on enamel surface of human teeth: An atomic force microscopy study’. Journal of the Mechanical Behavior of Biomedical Materials (JMBBM), Volume 110. Article No. 103930. Available online at https://doi.org/10.1016/j.jmbbm.2020.103930
Profile: Seungbum Hong, Ph.D.
Associate Professor
seungbum@kaist.ac.kr
http://mii.kaist.ac.kr/
Materials Imaging and Integration (MII) Lab.
Department of Materials Science and Engineering (MSE)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
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2020.07.21 View 10875 -
X-ray Scattering Shines Light on Protein Folding
- Multiple forms of a non-functional, unfolded protein follow different pathways and timelines to reach its folded, functional state, a study reveals. -
KAIST researchers have used an X-ray method to track how proteins fold, which could improve computer simulations of this process, with implications for understanding diseases and improving drug discovery. Their findings were reported in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30.
When proteins are translated from their DNA codes, they quickly transform from a non-functional, unfolded state into their folded, functional state. Problems in folding can lead to diseases like Alzheimer’s and Parkinson’s.
“Protein folding is one of the most important biological processes, as it forms the functioning 3D protein structure,” explained the physical chemist Hyotcherl Ihee of the Department of Chemistry at KAIST. Dr. Tae Wu Kim, the lead author of this research from Ihee’s group, added, “Understanding the mechanisms of protein folding is important, and could pave the way for disease study and drug development.”
Ihee’s team developed an approach using an X-ray scattering technique to uncover how the protein cytochrome c folds from its initial unfolded state. This protein is composed of a chain of 104 amino acids with an iron-containing heme molecule. It is often used for protein folding studies.
The researchers placed the protein in a solution and shined ultraviolet light on it. This process provides electrons to cytochrome c, reducing the iron within it from the ferric to the ferrous form, which initiates folding. As this was happening, the researchers beamed X-rays at very short intervals onto the sample. The X-rays scattered off all the atomic pairs in the sample and a detector continuously recorded the X-ray scattering patterns. The X-ray scattering patterns provided direct information regarding the 3D protein structure and the changes made in these patterns over time showed real-time motion of the protein during the folding process.
The team found cytochrome c proteins initially exist in a wide variety of unfolded states. Once the folding process is triggered, they stop by a group of intermediates within 31.6 microseconds, and then those intermediates follow different pathways with different folding times to reach an energetically stable folded state.
“We don’t know if this diversity in folding paths can be generalized to other proteins,” Ihee confessed. He continued, “However, we believe that our approach can be used to study other protein folding systems.”
Ihee hopes this approach can improve the accuracy of models that simulate protein interactions by including information on their unstructured states. These simulations are important as they can help identify barriers to proper folding and predict a protein’s folded state given its amino acid sequence. Ultimately, the models could help clarify how some diseases develop and how drugs interact with various protein structures.
Ihee’s group collaborated with Professor Young Min Rhee at the KAIST Department of Chemistry, and this work was supported by the National Research Foundation of Korea (NRF) and the Institute for Basic Science (IBS).
Figure. The scientists found that non-functional unfolded forms of the protein cytochrome c follow different pathways and timelines to reach a stable functional folded state.
Publications:
Kim, T. W., et al. (2020) ‘Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering’. PNAS. Volume 117. Issue 26. Page 14996-15005. Available online at https://doi.org/10.1073/pnas.1913442117
Profile: Hyotcherl Ihee, Ph.D.
Professor
hyotcherl.ihee@kaist.ac.kr
http://time.kaist.ac.kr/
Ihee Laboratory
Department of Chemistry
KAIST
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Young Min Rhee, Ph.D.
Professor
ymrhee@kaist.ac.kr
http://singlet.kaist.ac.kr
Rhee Research Group
Department of Chemistry
KAIST
https://www.kaist.ac.kr
Daejeon 34141, Korea
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2020.07.09 View 12807 -
Every Moment of Ultrafast Chemical Bonding Now Captured on Film
- The emerging moment of bond formation, two separate bonding steps, and subsequent vibrational motions were visualized. -
< Emergence of molecular vibrations and the evolution to covalent bonds observed in the research. Video Credit: KEK IMSS >
A team of South Korean researchers led by Professor Hyotcherl Ihee from the Department of Chemistry at KAIST reported the direct observation of the birthing moment of chemical bonds by tracking real-time atomic positions in the molecule. Professor Ihee, who also serves as Associate Director of the Center for Nanomaterials and Chemical Reactions at the Institute for Basic Science (IBS), conducted this study in collaboration with scientists at the Institute of Materials Structure Science of High Energy Accelerator Research Organization (KEK IMSS, Japan), RIKEN (Japan), and Pohang Accelerator Laboratory (PAL, South Korea). This work was published in Nature on June 24.
Targeted cancer drugs work by striking a tight bond between cancer cell and specific molecular targets that are involved in the growth and spread of cancer. Detailed images of such chemical bonding sites or pathways can provide key information necessary for maximizing the efficacy of oncogene treatments. However, atomic movements in a molecule have never been captured in the middle of the action, not even for an extremely simple molecule such as a triatomic molecule, made of only three atoms.
Professor Ihee's group and their international collaborators finally succeeded in capturing the ongoing reaction process of the chemical bond formation in the gold trimer. "The femtosecond-resolution images revealed that such molecular events took place in two separate stages, not simultaneously as previously assumed," says Professor Ihee, the corresponding author of the study. "The atoms in the gold trimer complex atoms remain in motion even after the chemical bonding is complete. The distance between the atoms increased and decreased periodically, exhibiting the molecular vibration. These visualized molecular vibrations allowed us to name the characteristic motion of each observed vibrational mode." adds Professor Ihee.
Atoms move extremely fast at a scale of femtosecond (fs) ― quadrillionths (or millionths of a billionth) of a second. Its movement is minute in the level of angstrom equal to one ten-billionth of a meter. They are especially elusive during the transition state where reaction intermediates are transitioning from reactants to products in a flash. The KAIST-IBS research team made this experimentally challenging task possible by using femtosecond x-ray liquidography (solution scattering). This experimental technique combines laser photolysis and x-ray scattering techniques. When a laser pulse strikes the sample, X-rays scatter and initiate the chemical bond formation reaction in the gold trimer complex. Femtosecond x-ray pulses obtained from a special light source called an x-ray free-electron laser (XFEL) were used to interrogate the bond-forming process. The experiments were performed at two XFEL facilities (4th generation linear accelerator) that are PAL-XFEL in South Korea and SACLA in Japan, and this study was conducted in collaboration with researchers from KEK IMSS, PAL, RIKEN, and the Japan Synchrotron Radiation Research Institute (JASRI).
Scattered waves from each atom interfere with each other and thus their x-ray scattering images are characterized by specific travel directions. The KAIST-IBS research team traced real-time positions of the three gold atoms over time by analyzing x-ray scattering images, which are determined by a three-dimensional structure of a molecule. Structural changes in the molecule complex resulted in multiple characteristic scattering images over time. When a molecule is excited by a laser pulse, multiple vibrational quantum states are simultaneously excited. The superposition of several excited vibrational quantum states is called a wave packet. The researchers tracked the wave packet in three-dimensional nuclear coordinates and found that the first half round of chemical bonding was formed within 35 fs after photoexcitation. The second half of the reaction followed within 360 fs to complete the entire reaction dynamics.
They also accurately illustrated molecular vibration motions in both temporal- and spatial-wise. This is quite a remarkable feat considering that such an ultrafast speed and a minute length of motion are quite challenging conditions for acquiring precise experimental data.
In this study, the KAIST-IBS research team improved upon their 2015 study published by Nature. In the previous study in 2015, the speed of the x-ray camera (time resolution) was limited to 500 fs, and the molecular structure had already changed to be linear with two chemical bonds within 500 fs. In this study, the progress of the bond formation and bent-to-linear structural transformation could be observed in real time, thanks to the improvement time resolution down to 100 fs. Thereby, the asynchronous bond formation mechanism in which two chemical bonds are formed in 35 fs and 360 fs, respectively, and the bent-to-linear transformation completed in 335 fs were visualized. In short, in addition to observing the beginning and end of chemical reactions, they reported every moment of the intermediate, ongoing rearrangement of nuclear configurations with dramatically improved experimental and analytical methods.
They will push this method of 'real-time tracking of atomic positions in a molecule and molecular vibration using femtosecond x-ray scattering' to reveal the mechanisms of organic and inorganic catalytic reactions and reactions involving proteins in the human body. "By directly tracking the molecular vibrations and real-time positions of all atoms in a molecule in the middle of reaction, we will be able to uncover mechanisms of various unknown organic and inorganic catalytic reactions and biochemical reactions," notes Dr. Jong Goo Kim, the lead author of the study.
Publications:
Kim, J. G., et al. (2020) ‘Mapping the emergence of molecular vibrations mediating bond formation’. Nature. Volume 582. Page 520-524. Available online at https://doi.org/10.1038/s41586-020-2417-3
Profile: Hyotcherl Ihee, Ph.D.
Professor
hyotcherl.ihee@kaist.ac.kr
http://time.kaist.ac.kr/
Ihee Laboratory
Department of Chemistry
KAIST
https://www.kaist.ac.kr
Daejeon 34141, Korea
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2020.06.24 View 15175 -
New Nanoparticle Drug Combination For Atherosclerosis
Physicochemical cargo-switching nanoparticles (CSNP) designed by KAIST can help significantly reduce cholesterol and macrophage foam cells in arteries, which are the two main triggers for atherosclerotic plaque and inflammation.
The CSNP-based combination drug delivery therapy was proved to exert cholesterol-lowering, anti-inflammatory, and anti-proliferative functions of two common medications for treating and preventing atherosclerosis that are cyclodextrin and statin. Professor Ji-Ho Park and Dr. Heegon Kim from KAIST’s Department of Bio and Brain Engineering said their study has shown great potential for future applications with reduced side effects.
Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of cholesterol and cholesterol-loaded macrophage foam cells in the intima. When this atherosclerotic plaque clogs and narrows the artery walls, they restrict blood flow and cause various cardiovascular conditions such as heart attacks and strokes. Heart attacks and strokes are the world’s first and fifth causes of death respectively.
Oral statin administration has been used in clinics as a standard care for atherosclerosis, which is prescribed to lower blood cholesterol and inhibit its accumulation within the plaque. Although statins can effectively prevent the progression of plaque growth, they have only shown modest efficacy in eliminating the already-established plaque. Therefore, patients are required to take statin drugs for the rest of their lives and will always carry the risk of plaque ruptures that can trigger a blood clot.
To address these issues, Professor Park and Dr. Kim exploited another antiatherogenic agent called cyclodextrin. In their paper published in the Journal of Controlled Release on March 10, Professor Park and Dr. Kim reported that the polymeric formulation of cyclodextrin with a diameter of approximately 10 nanometers(nm) can accumulate within the atherosclerotic plaque 14 times more and effectively reduce the plaque even at lower doses, compared to cyclodextrin in a non-polymer structure.
Moreover, although cyclodextrin is known to have a cytotoxic effect on hair cells in the cochlea, which can lead to hearing loss, cyclodextrin polymers developed by Professor Park’s research group exhibited a varying biodistribution profile and did not have this side effect.
In the follow-up study reported in ACS Nano on April 28, the researchers exploited both cyclodextrin and statin and form the cyclodextrin-statin self-assembly drug complex, based on previous findings that each drug can exert local anti-atherosclerosis effect within the plaque. The complex formation processes were optimized to obtain homogeneous and stable nanoparticles with a diameter of about 100 nm for systematic injection.
The therapeutic synergy of cyclodextrin and statin could reportedly enhance plaque-targeted drug delivery and anti-inflammation. Cyclodextrin led to the regression of cholesterol in the established plaque, and the statins were shown to inhibit the proliferation of macrophage foam cells. The study suggested that combination therapy is required to resolve the complex inflammatory cholesterol-rich microenvironment within the plaque.
Professor Park said, “While nanomedicine has been mainly developed for the treatment of cancers, our studies show that nanomedicine can also play a significant role in treating and preventing atherosclerosis, which causes various cardiovascular diseases that are the leading causes of death worldwide.”
This work was supported by KAIST and the National Research Foundation (NRF) of Korea.
Publications:
1. Heegon Kim, Junhee Han, and Ji-Ho Park. (2020) ‘Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity’ Journal of Controlled Release. Volume 319. Page 77-86. Available online at https://doi.org/10.1016/j.jconrel.2019.12.021
2. Kim, H., et al. (2020) ‘Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy’ ACS Nano. Available online at https://doi.org/10.1021/acsnano.9b08216
Profile: Ji-Ho Park, Ph.D.
Associate Professor
jihopark@kaist.ac.kr
http://openwetware.org/wiki/Park_Lab
Biomaterials Engineering Laboratory (BEL)
Department of Bio and Brain Engineering (BIOENG)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Heegon Kim, Ph.D.
Postdoctoral Researcher
heegon@kaist.ac.kr
BEL, BIOENG, KAIST
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2020.06.16 View 11934 -
Professor Jee-Hwan Ryu Receives IEEE ICRA 2020 Outstanding Reviewer Award
Professor Jee-Hwan Ryu from the Department of Civil and Environmental Engineering was selected as this year’s winner of the Outstanding Reviewer Award presented by the Institute of Electrical and Electronics Engineers International Conference on Robotics and Automation (IEEE ICRA). The award ceremony took place on June 5 during the conference that is being held online May 31 through August 31 for three months.
The IEEE ICRA Outstanding Reviewer Award is given every year to the top reviewers who have provided constructive and high-quality thesis reviews, and contributed to improving the quality of papers published as results of the conference.
Professor Ryu was one of the four winners of this year’s award. He was selected from 9,425 candidates, which was approximately three times bigger than the candidate pool in previous years. He was strongly recommended by the editorial committee of the conference.
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2020.06.10 View 7608