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A Novel Biosensor to Advance Diverse High-Level Production of Microbial Cell Factories
A research group at KAIST presented a novel biosensor which can produce diverse, high-level microbial cell factories. The biosensor monitors the concentration of products and even intermediates when new strains are being developed. This strategy provides a new platform for manufacturing diverse natural products from renewable resources. The team succeeded in creating four natural products of high-level pharmaceutical importance with this strategy.
Malonyl-CoA is a major building block for many value-added chemicals including diverse natural products with pharmaceutical importance. However, due to the low availability of malonyl-CoA in bacteria, many malonyl-CoA-derived natural products have been produced by chemical synthesis or extraction from natural resources that are harmful to the environment and are unsustainable. For the sustainable biological production of malonyl-CoA-derived natural products, increasing the intracellular malonyl-CoA pool is necessary. To this end, the development of a robust and efficient malonyl-CoA biosensor was required to monitor the concentration of intracellular malonyl-CoA abundance as new strains are developed.
Metabolic engineering researchers at KAIST addressed this issue. This research reports the development of a simple and robust malonyl-CoA biosensor by repurposing a type III polyketide synthase (also known as RppA), which produces flaviolin, a colorimetric indicator of malonyl-CoA. Subsequently, the RppA biosensor was used for the rapid and efficient colorimetric screening of gene manipulation targets enabling enhanced malonyl-CoA abundance. The screened beneficial gene targets were employed for the high-level production of four representative natural products derived from malonyl-CoA. Compared with the previous strategies, which were expensive and time-consuming, the new biosensor could be easily applied to industrially relevant bacteria including Escherichia coli, Pseudomonas putida, and Corynebacterium glutamicum to enable a one-step process.
The study employs synthetic small regulatory RNA (sRNA) technology to rapidly and efficiently reduce endogenous target gene expression for improved malonyl-CoA production. The researchers constructed an E. coli genome-scale synthetic sRNA library targeting 1,858 genes covering all major metabolic genes in E. coli. This library was employed with the RppA biosensor to screen for gene targets which are believed to be beneficial for enhancing malonyl-CoA accumulation upon their expression knockdown.
From this colorimetric screening, 14 gene targets were selected, all of which were successful at significantly increasing the production of four natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin). Although specific examples are demonstrated in E. coli as a host, the researchers showed that the biosensor is also functional in P. putida and C. glutamicum, industrially important representative gram-negative and gram-positive bacteria, respectively. The malonyl-CoA biosensor developed in this research will serve as an efficient platform for the rapid development of strains capable of producing natural products crucial for the pharmaceutical, chemical, cosmetics, and food industries.
An important aspect of this work is that the high-performance strains constructed in this research were developed rapidly and easily by utilizing the simple approach of colorimetric screening, without involving extensive metabolic engineering approaches. 6-Methylsalicylic acid (an antibiotic) could be produced to the highest titer reported for E. coli, and the microbial production of aloesone (a precursor of aloesin, an anti-inflammatory agent/whitening agent) was achieved for the first time.
“A sustainable process for producing diverse natural products using renewable resources is of great interest. This study represents the development of a robust and efficient malonyl-CoA biosensor generally applicable to a wide range of industrially important bacteria. The capability of this biosensor for screening a large library was demonstrated to show that the rapid and efficient construction of high-performance strains is feasible. This research will be useful for further accelerating the development process of strains capable of producing valuable chemicals to industrially relevant levels,” said Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, who led the research.
This study entitled “Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria,” was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on October 02.
PhD students Dongsoo Yang and Won Jun Kim, MS student Shin Hee Ha, research staff Mun Hee Lee, Research Professor Seung Min Yoo, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering and Dr. Jong Hyun Choi of the Applied Microbiology Research Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) participated in this research.
Figure: Type III polyketide synthase (RppA) as a malonyl-CoA biosensor. RppA converts five molecules of malonyl-CoA into one molecule of red-colored flaviolin. This schematic diagram shows the overall conceptualization of the malonyl-CoA biosensor by indicating that higher malonyl-CoA abundance leads to higher production and secretion of flaviolin, resulting in a deeper red color of the culture. This system was employed for the enhanced production of four representative natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin) from engineered E. coli strains.
2018.10.11 View 8489 -
Scientist of October, Professor Haeshin Lee
(Professor Haeshin Lee from the Department of Chemistry)
Professor Haeshin Lee from the Department of Chemistry received the ‘Science and Technology Award of October’ from the Ministry of Science and ICT and the National Research Foundation of Korea for his contribution to developing an antibleeding injection needle. This novel outcome will fundamentally prevent the problem of secondary infections of AIDS, Ebola and Hepatitis viruses transmitting from patients to medical teams.
This needle’s surface is coated with hemostatic materials. Its concept is simple and the key to this technology is to make materials that are firmly coated on the needle so that they can endure frictional force when being injected into skin and blood vessels. Moreover, the materials should be adhesive to skin and the interior of blood vessels, but harmless to humans.
Professor Lee found a solution from natural polymer ingredients. Catecholamine can be found in mussels. Professor Lee conjugated catechol groups on the chitosan backbone. He applied this mussel-inspired adhesive polymer Chitosan-catechol, which immediately forms an adhesive layer with blood, as a bioadhesion for the antibleeding injection needle.
Professor Lee said, “Chitosan-catechol, which copies the adhesive mechanism of mussels, shows high solubility in physiological saline as well as great mucoadhesion. Hence, it is perfectly suitable for coating the injection needle. Combining it with proteins allows for efficient drug delivery to the heart, which is a challenging injection location, so it will be also useful for treating incurable heart disease.”
2018.10.05 View 8414 -
The 1st Korea Toray Science and Technology Awardee, Prof. Sukbok Chang
(Distinguished Professor Sukbok Chang from the Department of Chemistry)
The Korea Toray Science Foundation (KTSF) awarded the first Korea Toray Science Technology Award in basic science to Distinguished Professor Sukbok Chang from the Department of Chemistry on September 19.
KTSF was established in January 2018, and its award goes to researchers who have significantly contributed to the development of chemistry and materials research with funds to support research projects.
Distinguished Professor Chang has devoted himself in organocatalysis research; in particular, his work on catalysts for effective lactam formation, which was an intricate problem, received great attention.
The award ceremony will take place in The Federation of Korean Industries Hall on October 31. KTFS board members, judges, and the CEO of Toray Industries Akihiro Nikkaku will attend the ceremony. Also, Dr. Ryoji Noyori, the Nobel Laureate in Chemistry, will give a talk on the role of chemistry and creative challenges as a researcher.
2018.10.04 View 7026 -
President Shin Presents Opportunities & Challenges of the 4IR at the Summer Davos Forum
(President Shin makes a keynote speech at the 2018 Summer Davos Forum in China on Sept.20.)
KAIST co-hosted the Asia Session with the World Economic Forum during the 2018 Summer Davos Forum in Tianjin, China from September 18 through 20. The session highlighted regional collaboration in Asia to promote inclusive growth in the Fourth Industrial Revolution.
KAIST is working closely with the WEF to take the lead in the Fourth Industrial Revolution. Last July, KAIST established the Fourth Industrial Revolution Information Center (FIRIC) at the KAIST Institute and signed an MOU with the Center for the Fourth Industrial Revolution (C4IR) at the WEF in October. The session is a follow-up event KAIST and the C4IR agreed to last year during the Roundtable Session held in Seoul.
Many experts in new emerging industries as well as many project directors, including Director Murat Sonmez of the C4IR, attended the session KAIST hosted. Director Chizuru Suga at the C4IR in Japan, Director Danil Kerimi in China, and Director Shailesh Sharda in India also attended the session and discussed ways to expand collaboration and networks among the countries.
In his keynote speech at the session on September 20, President Sung-Chul Shin presented how the Korean government is trying to drive the economy by strategically investing in focused industries in the new global industrial environment. President Shin introduced the government’s strategic roadmap to build the competitiveness of emerging technologies such as AI, blockchain, and precision medicine.
He also stressed that the three components of innovation, collaboration, and speed should be prioritized in all sectors for the successful realization of the Fourth Industrial Revolution. For instance, innovation in education, research, and technology commercialization, expansive domestic and international collaboration beyond the private and public sectors, speedy deregulation, and efficient governance will all be critical.
He also said that KAIST will launch new pilot collaboration projects along with the WEF soon. “We paved the way for leading the network with major countries including Japan and India for advancing the Fourth Industrial Revolution through this session,” President Shin said.
2018.09.21 View 6957 -
Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.)
A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources.
Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid
A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18.
There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways.
The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway.
In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption.
The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose.
Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.”
This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18 View 5900 -
Distinguished Professor Sang Yup Lee Announced as the Eni Award Recipient
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will be awarded the 2018 Eni Advanced Environmental Solutions Prize in recognition of his innovations in the fields of energy and environment. The award ceremony will take place at the Quirinal Palace, the official residence of Italian President Sergio Mattarella, who will also be attending on October 22.
Eni, an Italian multinational energy corporation established the Eni Award in 2008 to promote technological and research innovation of efficient and sustainable energy resources. The Advanced Environmental Solutions Prize is one of the three categories of the Eni Award. The other two categories are Energy Transition and Energy Frontiers. The Award for Advanced Environmental Solutions recognizes a researcher or group of scientists that has achieved internationally significant R&D results in the field of environmental protection and recovery. The Eni Award is referred to as the Nobel Award in the fields of energy and environment.
Professor Lee, a pioneering leader in systems metabolic engineering was honored with the award for his developing engineered bacteria to produce chemical products, fuels, and non-food biomass materials sustainably and with a low environmental impact. He has leveraged the technology to develop microbial bioprocesses for the sustainable and environmentally friendly production of chemicals, fuels, and materials from non-food renewable biomass.
The award committee said that they considered the following elements in assessing Professor Lee’s achievement: the scientific relevance and the research innovation level; the impact on the energy system in terms of sustainability as well as fairer and broader access to energy; and the adequacy between technological and economic aspects.
Professor Lee, who already won two other distinguished prizes such as the George Washington Carver Award and the PV Danckwerts Memorial Lecture Award this year, said, “I am so glad that the international academic community as well as global industry leaders came to recognize our work that our students and research team has made for decades.”
Dr. Lee’s lab has been producing a lot of chemicals in environmentally friendly ways. Among them, many were biologically produced for the first time and some of these processes have been already commercialized. “We will continue to strive for research outcomes with two objectives: First, to develop bio-based processes suitable for sustainable chemical industry. The other is to contribute to the human healthcare system through development of platform technologies integrating medicine and nutrition,” he added.
2018.09.12 View 6224 -
Center for Industrial Future Strategy Takes Off at KAIST
(Professor Wonjoon Kim from the School of Business and Technology Management)
Professors from KAIST and major international universities launched a mega-scale research center focusing on the Fourth Industrial Revolution, named the Center for Industrial Future Strategy (CIFS).
This center is funded by the National Research Foundation Korea and will receive 2.25 billion KRW over four years.
Directed by Professor Wonjoon Kim from the School of Business and Technology Management, the center is comprised of ten top-tier researchers and four research associates, including Professor Hawoon Jeong (KAIST), Professor Scott Stern (MIT), Professor Aaron Chatterji (Duke University), Dr. Yong Suk Lee (Stanford University) and Professor Hyejin Youn (Northwestern University).
The center will conduct research on technical, social, and economic changes derived by a new paradigm of technological innovation.
Moreover, they will study policies and strategies in relation to innovation in the corporate and government sectors to achieve economic growth in a sustainable manner. The center will also propose policies and strategies in a variety of economic and industrial settings to establish a sustainable and global innovation ecosystem.
To carry out these studies successfully, CIFS will further expand the AIEA-NBER Conference with the Asia Innovation and Entrepreneurship Association (AIEA) and the National Bureau of Economic Research (NBER) in which numerous Nobel Laureates in Economics are affiliated. They will also comprise thematic research teams with co-founding universities to build stronger cooperation with one another.
Besides the academic cooperation, the center will also build partnerships with international organizations, including the Asian Development Bank and the Inter-American Development Bank to carry out their missions at multilateral levels.
Their research topics include changes to value chains in a new paradigm of technological innovation, labor market changes in the Fourth Industrial Revolution, sharing economies and social interests, big data, artificial intelligence & privacy policy, and innovation & ethical and institutional countermeasures to AI technology.
Professor Kim said, “The new paradigm of technological innovation is evolving social, economic, and industrial structures, such as R&D, industry, technology, labor, finance, and institutions. The Center will contribute to proposing policies and strategies so that Korea, as well as the international community, can take appropriate measures to these big changes.”
2018.09.11 View 9071 -
NEREC Summer Program Keeps Fellows Thinking, Engaged in Nuclear Nonproliferation
Nuclear technology is more than just technology. It is the fruit of the most advanced science and technology. It also requires high standards of policymaking and global cooperation for benefiting the technology.
As part of the fifth annual Nuclear Nonproliferation Education and Research Center (NEREC) Summer Fellows Program at KAIST, 24 students from 15 countries participated in six-week intensive education and training program. NEREC is the only university-based center dedicated to nuclear nonproliferation education and research established in 2014.
The program, which provides multidisciplinary lectures and seminars on nuclear technology and policy as well as international relations, was designed to nurture global nuclear technology experts well equipped in three areas: in-depth knowledge of technology, applicability gained from sound policy building, and negotiating for international cooperation. It now has grown into the most popular summer program at KAIST.
During the program from July 6 to August 18, participants were able to engage in enriching and stimulating learning experiences in tandem with policies and technology for the utilization and provision of peaceful and safe nuclear technology.
Participating fellows also had to conduct a group research project on a given topic. This year, they explored nuclear nonproliferation issues in relation to nuclear exports and brainstormed some recommendations for current policy. They presented their outcomes at the 2018 NEREC Conference on Nuclear Nonproliferation. After intensive lecture sessions and group research work, the fellows went off to key policy think-tanks, nuclear research institutes, and research power facilities in Korea, Japan, and China.
“NEREC emphasizes nuclear nonproliferation issues related to civilian nuclear power and the associated nuclear fuel cycle development from the point of technology users. I am very glad that the number of participants are increasing year by year,” said the Director of NEREC Man-Sung Yim, a professor in the Department of Nuclear and Quantum Engineering.
Participants’ majors vary from nuclear engineering to international relations to economics. The fellows divided into two groups of graduate and undergraduate courses. They expressed their deep satisfactory in the multidisciplinary lectures by scholars from KAIST, Seoul National University, and Korea National Defense University.
Many participants reported that they learned a lot, not only about policy and international relations but on the research they are conducting and what the key issues will be in dealing for producing meaningful research work.
Moad Aldbissi from the KTH Royal Institute of Technology is one of the students who shared the same view. He said, “Coming from a technical background in nuclear engineering, I managed to learn a lot about nuclear policy and international relations. The importance of integrating the technical and political fields became even clearer.”
Most students concurred that they recognized how important it was to make international collaboration in this powerful field for each country through this program.
“As an engineering student, I just approached this program like an empty glass in policy areas. While working with colleagues during the program, I came to understand how important it is to make cooperation in these fields for the better result of national development and international relations,” said Thanataon Pornphatdetaudom from the Tokyo Institute of Technology.
To Director Yim, this program is becoming well positioned to educate nuclear policy experts in a number of countries of strategic importance. He believes the continuous supply of these experts will contribute to promoting global nuclear nonproliferation and the peaceful use of nuclear energy while the use of nuclear technology continues.
2018.09.04 View 8870 -
Adding Smart to Science Museum
KAIST and the National Science Museum (NSM) created an Exhibition Research Center for Smart Science to launch exhibitions that integrate emerging technologies in the Fourth Industrial Revolution, including augmented reality (AR), virtual reality (VR), Internet of Things (IoTs), and artificial intelligence (AI).
There has been a great demand for a novel technology for better, user-oriented exhibition services. The NSM continuously faces the problem of not having enough professional guides. Additionally, there have been constant complaints about its current mobile application for exhibitions not being very effective.
To tackle these problems, the new center was founded, involving 11 institutes and universities. Sponsored by the National Research Foundation, it will oversee 15 projects in three areas: exhibition-based technology, exhibition operational technology, and exhibition content.
The group first aims to provide a location-based exhibition guide system service, which allows it to incorporate various technological services, such as AR/VR to visitors. An indoor locating system named KAILOS, which was developed by KAIST, will be applied to this service. They will also launch a mobile application service that provides audio-based exhibition guides.
To further cater to visitors’ needs, the group plans to apply a user-centered ecosystem, a living lab concept to create pleasant environment for visitors.
“Every year, hundred thousands of young people visit the National Science Museum. I believe that the exhibition guide system has to be innovative, using cutting-edge IT technology in order to help them cherish their dreams and inspirations through science,” Jeong Heoi Bae, President of Exhibition and Research Bureau of NSM, emphasized.
Professor Dong Soo Han from the School of Computing, who took the position of research head of the group, said, “We will systematically develop exhibition technology and contents for the science museum to create a platform for smart science museums. It will be the first time to provide an exhibition guide system that integrates AR/VR with an indoor location system.”
The center will first apply the new system to the NSM and then expand it to 167 science museums and other regional museums.
2018.09.04 View 7288 -
Potential Drug to Cure Ciliopathies
(from left: Professor Joon Kim and PhD candidate Yong Joon Kim)
Ciliopathies are rare disorders involving functional and structural abnormalities of cilia. Although they are rare, they may reach 1 in 1,000 births. Unfortunately, there are no small-molecule drugs for treating ciliary defects. A KAIST research team conducted successful research that introduces a potential treatment that will be a foundation for developing drugs to treat the disease as well as a platform for developing small-molecule drugs for similar genetic disorders.
It was found that mutations in genes required for the formation or function of primary cilia cause ciliopathies and they result in cerebellar disorders, kidney dysfunction, and retinal degeneration.
Primary cilia are cell organelles playing a crucial role in the human body. They participate in intercellular signal transduction during embryonic development and allow retinal photoreceptor cells to function.
Currently, there are no approved drugs available for treating most ciliopathies. In fact, this is the case for most of the rare genetic disorders involving functional abnormalities through genetic mutation, and gene therapy is usually the only treatment available.
To tackle this issue, a team led by Professor Joon Kim from the Graduate School of Medical Science and Engineering and Ho Jeong Kwon from Yonsei University constructed a cell that mimics a gene-mutated CEP290, one of the main causes of ciliopathies, through genome editing. They then used cell-based compound library screening to obtain a natural small-molecule compound capable of relieving defects in ciliogenesis, the production of cilia.
The CEP290 protein forms a complex with a ciliopathy protein called NPHP5 to support the function of the ciliary transition zone. In cases where the CEP290 protein is not formed due to a genetic mutation, NPHP5 will not function normally. Here, the compound was confirmed to partially restore the function of the complex by normalizing the function of NPHP5.
The team also identified that the compound is capable of retarding retinal degeneration by injecting the compound into animal models.
As a result, they discovered a lead compound for developing medication to treat ciliopathy patients involving retinal degeneration. Hence, the findings imply that chemical compounds that target other proteins interacting with the disease protein can mitigate shortages of a disease protein in recessive genetic disorders.
PhD candidate Yong Joon Kim stated, “This study shows how genetic disorders caused by genetic mutation can be treated with small-molecule drugs.”
Professor Kim said, “Since the efficacy of the candidate drug has been verified through animal testing, a follow-up study will also be conducted to demonstrate the effect on humans.”
This research was published in the Journal of Clinical Investigation on July 23.
Figure 1. Identification of compounds that rescue ciliogenesis defects caused by CEP290 knockout
Figure 2. Eupatilin injection ameliorates M-opsin trafficking and electrophysiological response of cone photoreceptors in rd16 mice
2018.08.30 View 7370 -
'K-FLEX' Makes a Splash as a Flexible Endoscopic Surgical Robot
( Robot arms perform an incision during an ex-vivo test on a porcine gallbladder.)
K-FLEX, a flexible endoscopic surgical robot developed by the KAIST Future Medical Robotics Research Center, opens a new chapter for minimally invasive robot-assisted surgery with its precision control of 3.7 mm diameter robotic arms. The two arms, placing at the end of flexible endoscopes, highlight impeccable precision control and robust mini-joint design technologies. While cruising through the complicated inner body pliably, it carries out procedures on the spot with its robotic arms.
The research team under Professor Dong-Soo Kwon recently tested the device in-vivo, conducting a complicated endoscopic procedure dissecting a porcine gallbladder in collaboration with Professor Dae-Kyung Son of the National Cancer Center. The arms successfully manipulated the tissue safely.
During the test, K-FLEX, inserted through an incision in the navel, snaked through the narrow passages of the complicated inner organs. When reaching the desired spot, one of the robot arms pushed aside and held up the nearby tissue to secure proper vision and space for the procedure. Meanwhile, a cautery needle mounted at the tip of the other hand removed the lesion tissue on the gallbladder. The tiny camera installed at the front of the robot arms relayed the internal conditions. The full procedure was able to be monitored from the master console.
The two arms are placed onto 4.2 mm internal channels of an endoscope which is 17 mm in diameter. The arms can be deployable forward and backward and are extendable up to 7 cm for performing procedures.
K-FLEX is made of domestically produced components, except for the endoscopic module. It will expand new medical robotics research while offering novel therapeutic capabilities for endoscopes.
Flexible endoscopes are very promising for surgical applications because they can treat areas thought to be difficult to reach, such as the posterior side of an organ. Current rigid-type laparoscopic tools could not reach a lesion if it occurs in such serpentine and complicated areas. However, this flexible endoscopic surgery robot will bypass obstacles to reach the troubled area.
The ability to seamlessly integrate effective actuation into millimeter-scale deployable mechanisms fits well with minimally invasive surgical procedures. This flexible endoscopic surgery robot, only half the size of current laparoscopic surgical robots, is deployable into natural orifices such as the mouth, anus, and vagina without requiring external incisions. Laparoscopic devices and robots require at least three to four external incisions to insert the devices; however, the applicability of internal incisions reduces the possibility of complications arousing from excessive bleeding and bacterial infections.
Despite these advantages, it has remained challenging to manipulate the robotic arms of flexible endoscopes with integrated grabbing force, flexibility, and multiple degrees of freedom for clinical environments.
The team focused on smaller but smarter devices. Dr. Min-Ho Hwang, a principal researcher of K-FLEX, said that developing tiny robots that are able to generate the necessary forces without compromising safety was the challenge. They created a robust but smaller-joint technology that can exert a relatively greater force even into millimeter scale.
Professor Kwon said, “K-FLEX is the first flexible endoscopic surgery robot in Korea. We already confirmed the clinical adaptation through ex vivo tests and will see complete commercialization in two to three years.” The team believes K-FLEX will be very effective for surgery on incipient cancer cells in the stomach, colon, and thyroid.
Professor Kwon and his eight researchers recently established a tech start-up called EasyEndo Surgical Inc. with these core technologies. In June, K-FLEX won the ‘Best Application Award’ and the ‘Overall Winner’ at the Surgical Robot Challenge 2018 held at Imperial College London. The Korea Research Foundation funded the research on K-FLEX.
(The team conducts a procedure using K-FLEX, flexible endoscopic surgical robot.)
2018.08.17 View 7815 -
The MSE/CBE Int'l Workshop Explores Big Ideas in Emerging Materials
(KAIST President Sung-Chul Shin with scholars participated in the workshop)
The MSE/CBE International Workshop brought together editors from key academic journals in multidisciplinary materials science and scholars from leading universities at KAIST on Aug. 7.
The workshop hosted ten distinguished speakers in the fields of nanostructures for next-generation emerging applications, chemical and bio-engineering, and materials innovation for functional applications. They explored opportunities and challenges for reinventing novel materials that will solve complex problems.
(From left: Professor Buriak, Professor Swager and Professor Il-Doo Kim)
Speakers included: Chief Editor of Nature Materials Vincent Dusastre; Editor-in- Chief of ACS NANO and professor at UCLA Paul S. Weiss; Jillian M. Buriak, Editor-in-Chief of Chemistry of Materials; Associate Editor of Macromolecules and professor at MIT Timothy M. Swager; Coordinating Editor of Acta Materialia and Head of the Department of Materials Science and Engineering at MIT Christopher A. Schuh; Editor-in-Chief of Biotechnology Journal and Metabolic Engineering and Distinguished Professor at KAIST Sang-Yup Lee; Associate Editor of Energy Storage Materials and professor at KAIST Sang Ouk Kim; Professor Jeffrey C. Grossman at MIT; Professor Zhenan Bao at Stanford University; and Professor Hyuck Mo Lee, head of the Department of Materials Science and Engineering at KAIST.
Interdisciplinary materials research holds the key to building technological competitiveness in many industrial sectors extending from energy, environment, and health care to medicine and beyond. It has also been the bedrock of KAIST’s scholarship and research innovation. More than 200 faculty members in the field of materials science produce about 800 SCI papers every year. The two departments of materials science and chemical biomolecular engineering are leading KAIST’s global reputation, as they were both ranked 13th and 14th in the QS World University Ranking by Subject this year.
(Professor Il-Doo Kim fromt he Department of Materials Science Engineering)
Professor Il-Doo Kim from the Department of Materials Science Engineering has been the chair of this workshop from 2016. In hosting the second one this year, he said that he hopes this year’s workshop will inspire many materials scientists to have big ideas and work to make those big ideas get noticed in order to have a real impact.
(KAIST President Sung-Chul Shin)
President Sung-Chul Shin, who is a physicist specializing in materials physics, expressed his keen interest in the workshop, saying innovative materials made of unthinkable and noble combinations will be the key factor in determining the competitiveness of new technology and new industries. He lauded international collaborations for making new materials and the scholarly passion to evaluate the materials’ characteristics that made this significant progress possible.
Dr. Vincent Dusastre, chief editor of Nature Materials, presented recent trends in materials for energy. He described how the rational design and improvement of materials’ properties can lead to energy alternatives which will compete with existing technologies. He pointed out that given the dramatic fundamental and practical breakthroughs that are taking place in the realization of solar cells with high energy-conversion efficiency, the improvement of batteries for electric vehicles and the grid is also a major challenge. He stressed, “Key advances in sustainable approaches beyond Li-ion batteries and control of redox processes are also greatly needed.”
Meanwhile, ACS NANO Editor-in-Chief Paul S. Weiss spoke on the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. He stressed that such extensiveness of multi-interdisciplinary research will accelerate a greater impact as indicated when the fields of neuroscience and microbiome converged with nanoscience and nanotechnology.
Editor-in-Chief of Chemistry of Materials Professor Jillian M. Buriak from the University of Alberta described how predictive models and machine learning can replace time consuming empirical device production and screening. By understanding and pinpointing the frustrating bottlenecks in the design of stable and efficient organic photovoltaics, much faster throughput can be obtained to enable a more direct pathway to stability, efficiency, and finally commercialization.
2018.08.13 View 10956