research
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Using Light to Treat Alzheimer's Disease
Medical application of photoactive chemicals offers a promising therapeutic strategy for neurodegenerative diseases.
A research team jointly led by Professor Chan Beum Park of the Materials Science and Engineering Department at KAIST and Dr. Kwon Yu from the Bionano Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) conducted research to suppress an abnormal assembly of beta-amyloids, a protein commonly found in the brain, by using photo-excited porphyrins.
Beta-amyloid plaques are known to cause Alzheimer's disease. This research finding suggests new ways to treat neurodegenerative illnesses including Alzheimer's disease. It was published online as the lead article in the September 21th issue of Angewandte Chemie. The title of the article is “Photo-excited Porphyrins as a Strong Suppressor of ß-Amyloid Aggregation and Synaptic Toxicity.”
Light-induced treatments using organic photosensitizers have advantages to managing the treatment in time and area. In the case of cancer treatments, doctors use photodynamic therapies where a patient is injected with an organic photosensitizer, and a light is shed on the patient’s lesion. However, such therapies had never been employed to treat neurodegenerative diseases.
Alzheimer's starts when a protein called beta-amyloid is created and deposited in a patient’s brain. The abnormally folded protein created this way harms the brain cells by inducing the degradation of brain functions, for example, dementia. If beta-amyloid creation can be suppressed at an early stage, the formation of amyloid deposits will stop. This could prevent Alzheimer’s disease or halt its progress.
The research team effectively prevented the buildup of beta-amyloids by using blue LED lights and a porphyrin inducer, which is a biocompatible organic compound. By absorbing light energy, a photosensitizer such as porphyrin reaches the excitation state. Active oxygen is created as the porphyrin returns to its ground state. The active oxygen oxidizes a beta-amyloid monomer, and by combining with it, disturbs its assembly.
The technique was tested on drosophilae or fruit flies, which were produced to model Alzheimer on invertebrates. The research showed that symptoms of Alzheimer's disease in the fruit flies such as damage on synapse and muscle, neuronal apoptosis, degradation in motility, and decreased longevity were alleviated. Treatments with light provide additional benefits: less medication is needed than other drug treatments, and there are fewer side effects. When developed, photodynamic therapy will be used widely for this reason.
Professor Park said, “This work has significance as it was the first case to use light and photosensitizers to stop deposits of beta-amyloids. We plan to carry the research further by testing compatibility with other organic and inorganic photosensitizers and by changing the subject of photodynamic therapy to vertebrate such as mice.”
Picture 1 – Deposits of Beta-Amyloid in Fruit Flies Stopped by Using Porphyrin and Blue LED Lights
Picture 2 – The Research Finding Published as the Lead Article in Angewandte Chemie (September 2015)
2015.11.11 View 11499 -
Membrane
Scientists at KAIST have developed a new way of making fuel cell membranes using nanoscale fasteners, paving the way for lower-cost, higher-efficiency and more easily manufactured fuel cells.
The internal workings of fuel cells vary, but basically all types mix hydrogen and oxygen to produce a chemical reaction that delivers usable electricity and exhausts ordinary water as a by-product. One of the most efficient types is the proton exchange membrane (PEM) fuel cell, which operates at low enough temperatures to be used in homes and vehicles.
To generate electricity, PEM fuel cells rely on two chemical compartments separated by a permeable catalyst membrane. This membrane acts as an electrolyte; a negative electrode is bonded to one side of the membrane and a positive electrode is bonded to the other. The electrolyte membrane is often based on a polymer of perfluorosulfonic acid. Due to its high cost, however, a less expensive hydrocarbon-based electrolyte membrane has attracted interest in this technology sector.
Until now, the challenge in adopting such a hydrocarbon membrane has been that the interface between the electrode and hydrocarbon membrane is weak. This causes the membrane to delaminate relatively easily, falling apart and losing efficiency with use.
Professor Hee-Tak Kim of the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST) and his research team have developed a new fastening system that bonds the two materials mechanically rather than chemically. This opens the way to the development of fuel cell membranes that are less expensive, easier to manufacture, stronger and more efficient.
The researchers achieved this by moulding a pattern of tiny cylindrical pillars on the face of the hydrocarbon membrane. The pillars protrude into a softened skin of the electrode with heat. The mechanical bond sets and strengthens as the material cools and absorbs water. The pillar-patterned hydrocarbon membrane is cast using silicone moulds.
Professor Kim said, “This physically fastened bond is almost five times stronger and harder to separate than current bonds between the same layers.”
The new interlocking method also appears to offer a way to bond many types of hydrocarbon membranes that, until now, have been rejected because they couldn’t be fastened robustly. This would make hydrocarbon membranes practical for a number of applications beyond fuel cells such as rechargeable “redox flow” batteries.
The research team is now developing a stronger and more scalable interlocking interface for their nanoscale fasteners.
Picture: Schematic Diagram of the Fabrication of the Pillar P-SPAES Membrane and Its Working Principle of Interlocking Effects
2015.11.06 View 10296 -
Mapping the Folding Process of a Single Membrane Protein
KAIST and UCLA scientists were able to observe an individual membrane protein fold and unfold by pulling and releasing magnetically trapped protein molecules.
Proteins are huge molecules containing hundreds to thousands of atoms that adopt a unique three dimensional structure, placing chemical groups in just the right place to catalyze reactions or build cellular structures. How all those atoms manage to find the right location - the so-called folding problem - has fascinated molecular biologists since the first structures were seen in the 1950s. Moreover, folding has important medical implications because most genetic defects cause protein misfolding.
About a third of all proteins float around in the cell membrane where they ensure the right chemicals get in the cell in the right amounts. Membrane proteins also provide key information links between the cell and its environment. Indeed, most drugs target membrane proteins. Nevertheless, the folding of membrane proteins has been particularly difficult to study and has rarely been studied in natural environments, leaving the folding process for a large fraction of the protein universe still largely cloaked in mystery.
In a recent issue of Nature Chemical Biology, published on October 19, 2015, a research team led by Tae-Young Yoon of the Department of Physics at the Korea Advanced Institute of Science and Technology (KAIST) and James U. Bowie of the Department of Chemistry and Biochemistry at the University of California, Los Angeles (UCLA), report a new method for manipulating the folding of membrane proteins in a membrane environment using a tool called a magnetic tweezer.
Researchers first attach long DNA handles to the ends of the protein. One handle is attached to a glass surface and the other to a magnetic bead. Using a magnet, they can essentially grab the protein and pull on it, inducing it to unfold. By playing with the bead attached to the protein, they can force the protein to unfold or allow it to refold, and watch all this happening by 3D-tracking of the magnetic bead. With this novel strategy, they were able to quantitatively map the folding energy landscape, the folding kinetic rate, and folding intermediates of a membrane protein in a membrane environment for the first time.
“I have been dreaming about this experiment for a decade. To see it work so well is really gratifying,” said Dr. Bowie.
One of the major surprises in the study was that essentially all the atoms of the protein jump into the correct structure together. The researchers expected that the protein structure would come together in a more piecemeal fashion, with different parts of the structure forming separately, but that was not the case. It is possible that nature evolved such a smooth, highly cooperative folding process to prevent partially folded forms that could get into trouble in the crowded cell membrane. On the other hand, the cooperative folding seen here might not apply to other membrane proteins.
“We need to look at more proteins. The technique developed here may allow us to do just that,” said Dr. Yoon.
The single molecule mechanical manipulation technique could enable detailed folding studies of many other membrane proteins. A major barrier to the study of membrane proteins previously is that the proteins tend to stick together and get tangled up, as computer cords lying at your feet tend to do. With the tweezer technique used in this work, the protein cords are held apart from other cords so they can’t get knotted up. It is hoped that the new approach will open up an important part of the protein universe to scrutiny, including many proteins that become misfolded in disease states.
The title of the research paper is “Mapping the energy landscape for second-stage folding of a single membrane protein” (DOI: 10.1038/nchembio.1939).
Picture: Single-molecule magnetic tweezers that induce mechanical unfolding and refolding of a single membrane protein. Since the force applied is parallel to the biological lipid membrane, the unfolding and refolding processes occur within the membrane.
2015.10.20 View 10036 -
Establishment of System Metabolic Engineering Strategies
Although conventional petrochemical processes have generated chemicals and materials which have been useful to mankind, they have also triggered a variety of environmental problems including climate change and relied too much on nonrenewable natural resources. To ameliorate this, researchers have actively pursued the development of industrial microbial strains around the globe in order to overproduce industrially useful chemicals and materials from microbes using renewable biomass. This discipline is called metabolic engineering.
Thanks to advances in genetic engineering and our knowledge of cellular metabolism, conventional metabolic engineering efforts have succeeded to a certain extent in developing microbial strains that overproduce bioproducts at an industrial level. However, many metabolic engineering projects launched in academic labs do not reach commercial markets due to a failure to fully integrate industrial bioprocesses.
In response to this, Distinguished Professor Sang Yup Lee and Dr. Hyun Uk Kim, both from the Department of Chemical and Biomolecular Engineering at KAIST, have recently suggested ten general strategies of systems metabolic engineering to successfully develop industrial microbial strains. Systems metabolic engineering differs from conventional metabolic engineering by incorporating traditional metabolic engineering approaches along with tools of other fields, such as systems biology, synthetic biology, and molecular evolution.
The ten strategies of systems metabolic engineering have been featured in Nature Biotechnology released online in October 2015, which is entitled "Systems strategies for developing industrial microbial strains."
The strategies cover economic, state-of-the-art biological techniques and traditional bioprocess aspects. Specifically, they consist of: 1) project design including economic evaluation of a target bioproduct; 2) selection of host strains to be used for overproduction of a bioproduct; 3) metabolic pathway reconstruction for bioproducts that are not naturally produced in the selected host strains; 4) increasing tolerance of a host strain against the bioproduct; 5) removing negative regulatory circuits in the microbial host limiting overproduction of a bioproduct; 6) rerouting intracellular fluxes to optimize cofactor and precursor availability necessary for the bioproduct formation; 7) diagnosing and optimizing metabolic fluxes towards product formation; 8) diagnosis and optimization of microbial culture conditions including carbon sources; 9) system-wide gene manipulation to further increase the host strain's production performance using high-throughput genome-scale engineering and computational tools; and 10) scale-up fermentation of the developed strain and diagnosis for the reproducibility of the strain's production performance.
These ten strategies were articulated with successful examples of the production of L-arginine using Corynebacterium glutamicum, 1,4-butanediol using Escherichia coli, and L-lysine and bio-nylon using C. glutamicum.
Professor Sang Yup Lee said, "At the moment, the chance of commercializing microbial strains developed in academic labs is very low. The strategies of systems metabolic engineering outlined in this analysis can serve as guidelines when developing industrial microbial strains. We hope that these strategies contribute to improving opportunities to commercialize microbial strains developed in academic labs with drastically reduced costs and efforts, and that a large fraction of petroleum-based processes will be replaced with sustainable bioprocesses."
Lee S. Y. & Kim, H. U. Systems Strategies for Developing Industrial Microbial Strains. Nature Biotechnology (2015).
This work was supported by the Technology Development Program to Solve Climate Change on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556) and by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) from the Ministry of Science, ICT and Future Planning (MSIP), Korea, and through the National Research Foundation (NRF) of Korea. This work was also supported by the Novo Nordisk Foundation.
Picture: Concept of the Systems Metabolic Engineering Framework
(a) Three major bioprocess stages (b) Considerations in systems metabolic engineering to optimize the whole bioprocess. List of considerations for the strain development and fermentation contribute to improving microbial strain's production performance (red), whereas those for the separation and purification help in reducing overall operation costs by facilitating the downstream process (blue). Some of the considerations can be repeated in the course of systems metabolic engineering.
2015.10.19 View 11111 -
Discovery of Redox-Switch of KEenzyme Involved in N-Butanol Biosynthesis
Research teams at KAIST and Kyungpook National University (KNU) have succeeded in uncovering the redox-switch of thiolase, a key enzyme for n-butanol production in Clostridium acetobutylicum, one of the best known butanol-producing bacteria.
Biological n-butanol production was first reported by Louis Pasteur in 1861, and the bioprocess was industrialized usingClostridium acetobutylicum. The fermentation process by Clostridium strains has been known to be the most efficient one for n-butanol production. Due to growing world-wide issues such as energy security and climate change, the biological production of n-butanol has been receiving much renewed interest. This is because n-butanol possesses much better fuel characteristics compared to ethanol, such as higher energy content (29.2 MJ/L vs 19.6 MJ/L), less corrosiveness, less hygroscopy, and the ease with which it can be blended with gasoline and diesel.
In the paper published in Nature Communications, a broad-scope, online-only, and open access journal issued by the Nature Publishing Group (NPG), on September 22, 2015, Professor Kyung-Jin Kim at the School of Life Sciences, KNU, and Distinguished Professor Sang Yup Lee at the Department of Chemical and Biomolecular Engineering, KAIST, have proved that the redox-switch of thiolase plays a role in a regulation of metabolic flux in C. acetobutylicum by using in silico modeling and simulation tools.
The research team has redesigned thiolase with enhanced activity on the basis of the 3D structure of the wild-type enzyme. To reinforce a metabolic flux toward butanol production, the metabolic network of C. acetobutylicum strain was engineered with the redesigned enzyme. The combination of the discovery of 3D enzyme structure and systems metabolic engineering approaches resulted in increased n-butanol production in C. acetobutylicum, which allows the production of this important industrial chemical to be cost competitive.
Professors Kim and Lee said, "We have reported the 3D structure of C. acetobutylicum thiolase-a key enzyme involved in n-butanol biosynthesis, for the first time. Further study will be done to produce butanol more economically on the basis of the 3D structure of C. acetobutylicum thiolase."
This work was published online in Nature Communications on September 22, 2015.
Reference: Kim et al. "Redox-switch regulatory mechanism of thiolase from Clostridium acetobutylicum," Nature Communications
This research was supported by the Technology Development Program to Solve Climate Changes from the Ministry of Education, Science and Technology (MEST), Korea, the National Research Foundation of Korea, and the Advanced Biomass Center through the Global Frontier Research Program of the MEST, Korea.
For further information, contact Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea (leesy@kaist.ac.kr, +82-42-350-3930); and Dr. Kyung-Jin Kim, Professor, KNU, Daegu, Korea (kkim@knu.ac.kr, +82-53-950-6088).
Figure 1: A redox-switch of thiolase involves in butanol biosynthesis in Clostridium acetobutylicum. Thiolase condenses two acetyl-CoA molecules for initiating four carbon flux towards butanol.
Figure 2: Thiolase catalyzes the condensation reaction of acetyl-CoA to acetoacetyl-CoA. Two catalytic cysteine residues at 88th and 378th are oxidized and formed an intermolecular disulfide bond in an oxidized status, which results in inactivation of the enzyme for n-butanol biosynthesis. The intermolecular disulfide bond is broken enabling the n-butanol biosynthesis, when the environment status is reduced.
2015.09.23 View 11001 -
KAIST's Mathematician Reveals the Mechanism for Sustaining Biological Rhythms
Our bodies have a variety of biological clocks that follow rhythms or oscillations with periods ranging from seconds to days. For example, our hearts beat every second, and cells divide periodically. The circadian clock located in the hypothalamus generates twenty-four hour rhythms, timing our sleep and hormone release. How do these biological clocks or circuits generate and sustain the stable rhythms that are essential to life?
Jae Kyoung Kim, who is an assistant professor in the Department of Mathematical Sciences at KAIST, has predicted how these biological circuits generate rhythms and control their robustness, utilizing mathematical modeling based on differential equations and stochastic parameter sampling. Based on his prediction, using synthetic biology, a research team headed by Matthew Bennett of Rice University constructed a novel biological circuit that spans two genetically engineered strains of bacteria, one serves as an activator and the other as a repressor to regulate gene expression across multiple cell types, and found that the circuit generates surprisingly robust rhythms under various conditions.
The results of the research conducted in collaboration with KAIST (Korea Institute of Science and Technology), Rice University, and the University of Houston were published in Science (August 28, 2015 issue). The title of the paper is "Emergent Genetic Oscillations in a Synthetic Microbial Consortium" .
The top-down research approach, which focuses on identifying the components of biological circuits, limits our understanding of the mechanisms in which the circuits generate rhythms. Synthetic biology, a rapidly growing field at the interface of biosciences and engineering, however, uses a bottom-up approach.
Synthetic biologists can create complex circuits out of simpler components, and some of these new genetic circuits are capable of fluctuation to regulate gene production. In the same way that electrical engineers understand how an electrical circuit works as they construct batteries, resistors, and wires, synthetic biologists can understand better about biological circuits if they put them together using genes and proteins. However, due to the complexity of biological systems, both experiments and mathematical modeling need to be applied hand in hand to design these biological circuits and understand their function.
In this research, an interdisciplinary approach proved that a synthetic intercellular singling circuit generates robust rhythms to create a cooperative microbial system. Specifically, Kim's mathematical analysis suggested, and experiments confirmed, that the presence of negative feedback loops in addition to a core transcriptional negative feedback loop can explain the robustness of rhythms in this system. This result provides important clues about the fundamental mechanism of robust rhythm generation in biological systems.
Furthermore, rather than constructing the entire circuit inside a single bacterial strain, the circuit was split among two strains of Escherichia coli bacterium. When the strains were grown together, the bacteria exchanged information, completing the circuit. Thus, this research also shows how, by regulating individual cells within the system, complex biological systems can be controlled, which in turn influences each other (e.g., the gut microbiome in humans).
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Ye Chen, a graduate student in Bennett's laboratory at Rice University, and Jae Kyoung Kim, an assistant professor at KAIST and a former postdoctoral fellow at Ohio State University, are the lead authors of the paper. The co-authors are Rice graduate student Andrew Hirning and Krešimir Josic?, a professor of mathematics at the University of Houston. Bennett is the Assistant Professor of the Biochemistry and Cell Biology Department at Rice University.
About the researcher: While Jae Kyoung Kim is a mathematician, he has also solved various biological puzzles in collaboration with various experimental laboratories of Matthew Bennett at Rice University, David Virshup at Duke and the National University of Singapore, Carla Finkielstein at Virginia Polytechnic Institute and State University, Choo-Gon Lee at the Florida State University, Seung-Hee Yoo at the Medical School of the University of Texas, Toru Takumi at RIKEN Brain Science Institute, and Travis Wager at Pfizer Inc. He has used non-linear dynamics and stochastic analysis to understand the function of biochemical networks in biological systems. In particular, he is interested in mechanisms generating and regulating biological rhythms.
Picture 1: This schematic image is the design of a biological circuit between two strains of bacteria and the part of differential equations used to understand the function of the biological circuit.
Picture 2: The core transcriptional negative feedback loop and additional negative feedback loop in the biological circuit (picture 1) generate robust rhythms. The snapshots correspond the red dots in the time series graph.
2015.08.31 View 8910 -
'Engineered Bacterium Produces 1,3-Diaminopropane'
A research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported, for the first time, the production of 1,3-diaminopropane via fermentation of an engineered bacterium.
1,3-Diaminopropane is a three carbon diamine, which has a wide range of industrial applications including epoxy resin and cross-linking agents, as well as precursors for pharmaceuticals, agrochemicals, and organic chemicals. It can also be polymerized with dicarboxylic acids to make polyamides (nylons) for use as engineering plastics, medical materials, and adhesives.
Traditionally, 1,3-diaminopropane is derived from petroleum-based processes. In effort to address critical problems such as the depletion of petroleum and environmental issues inherent to the petroleum-based processes, the research team has developed an Escherichia coli (E. coli) strain capable of producing 1,3-diaminopropane. Using this technology, 1,3-diaminopropane can now be produced from renewable biomass instead of petroleum.
E. coli as found in nature is unable to produce 1,3-diaminopropane. Metabolic engineering, a technology to transform microorganisms into highly efficient microbial cell factories capable of producing chemical compounds of interest, was utilized to engineer the E. coli strain. First, naturally existing metabolic pathways for the biosynthesis of 1,3-diaminopropane were introduced into a virtual cell in silico to determine the most efficient metabolic pathway for the 1,3-diaminopropane production. The metabolic pathway selected was then introduced into an E. coli strain and successfully produced 1,3-diaminopropane for the first time in the world.
The research team applied metabolic engineering additionally, and the production titer of 1,3-diaminopropane increased about 21 fold. The Fed-batch fermentation of the engineered E. coli strain produced 13 grams per liter of 1,3-diaminoproapne. With this technology, 1,3-diaminopropane can be produced using renewable biomass, and it will be the starting point for replacing the current petroleum-based processes with bio-based processes.
Professor Lee said, “Our study suggested a possibility to produce 1,3-diaminopropane based on biorefinery. Further study will be done to increase the titer and productivity of 1,3-diaminopropane.”
This work was published online in Scientific Reports on August 11, 2015.
Reference: Chae, T.U. et al. "Metabolic engineering of Escherichia coli for the production of 1,3-diaminopropane, a three carbon diamine," Scientific Reports:
http://www.nature.com/articles/srep13040
This research was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) of Korea.
Figure 1: Metabolic engineering strategies for 1,3-diaminopropane production using C4 pathway
Figure 2: Fed-batch fermentation profiles of two final engineered E. coli strains
2015.08.12 View 11280 -
KAIST Develops Fiber-Like Light-Emitting Diodes for Wearable Displays
Professor Kyung-Cheol Choi and his research team from the School of Electrical Engineering at KAIST have developed fiber-like light-emitting diodes (LEDs), which can be applied in wearable displays. The research findings were published online in the July 14th issue of Advanced Electronic Materials.
Traditional wearable displays were manufactured on a hard substrate, which was later attached to the surface of clothes. This technique had limited applications for wearable displays because they were inflexible and ignored the characteristics of fabric.
To solve this problem, the research team discarded the notion of creating light-emitting diode displays on a plane. Instead, they focused on fibers, a component of fabrics, and developed a fiber-like LED that shared the characteristics of both fabrics and displays.
The essence of this technology, the dip-coating process, is to immerse and extract a three dimensional (3-D) rod (a polyethylene terephthalate fiber) from a solution, which functions like thread. Then, the regular levels of organic materials are formed as layers on the thread.
The dip-coating process allows the layers of organic materials to be easily created on the fibers with a 3-D cylindrical structure, which had been difficult in existing processes such as heat-coating process. By controlling of the withdrawal rate of the fiber, the coating's thickness can also be adjusted to the hundreds of thousandths of a nanometer.
The researchers said that this technology would accelerate the commercialization of fiber-based wearable displays because it offers low-cost mass production using roll-to-roll processing, a technology applied to create electronic devices on a roll of flexible plastics or metal foils.
Professor Choi said, “Our research will become a core technology in developing light emitting diodes on fibers, which are fundamental elements of fabrics. We hope we can lower the barrier of wearable displays entering the market.”
The lead author of the published paper, Seon-Il Kwon, added, “This technology will eventually allow the production of wearable displays to be as easy as making clothes.”
Picture 1: The Next Generation Wearable Display Using Fiber-Based Light-Emitting Diodes
Picture 2: Dip-Coating Process to Create Fiber-Based Light-Emitting Diodes
Picture 3: Fiber-Based Light-Emitting Diodes
2015.08.11 View 13374 -
Affordable Genetic Diagnostic Technique for Target DNA Analysis Developed
Professor Hyun-Gyu Park of the Department of Chemical and Biomolecular Engineering at KAIST has developed a technique to analyze various target DNAs using an aptamer, a DNA fragment that can recognize and bind to a specific protein or enzyme. This technique will allow the development of affordable genetic diagnoses for new bacteria or virus, such as Middle Ease Respiratory Syndrome (MERS). The research findings were published in the June issue of Chemical Communications, issued by the Royal Society of Chemistry in the United Kingdom. The paper was selected as a lead article of the journal.
The existing genetic diagnosis technique, based on molecular beacon probes, requires a new beacon probe whenever a target DNA mutates. As a result, it was costly to analyze various target DNA fragments. To address this problem, Professor Park’s team designed an aptamer that binds and deactivates DNA polymerase. The technique was used in reverse, so that the aptemer did not bind to the polymerase, maintaining its activated state, only if the target DNA was present. These probes are called TagMan probes.
The controlled activation and deactivation of DNA polymerase enables nucleic acid to elongate or dwindle, making it possible to measure fluorescence signals coming from TaqMan probes. This same probe can be used to detect various target DNAs, leading to the development of a new and sensitive genetic diagnostic technique.
Unlike the existing molecular beacon probe technique which requires a new probe for every target DNA, this new technique uses the same fluorescent TaqMan probe, which is cheaper and easier to detect a number of different target nucleic acid fragments. The application of this technique will make the process of identifying and detecting foreign DNAs from pathogens such as virus and bacteria more affordable and simple.
Professor Park said, “This technique will enable us to develop simpler diagnostic kits for new pathogens, such as MERS, allowing a faster response to various diseases. Our technology can also be applied widely in the field of genetic diagnostics.”
Picture: A schematic image of target nucleic acid extracted through the activation and deactivation of DNA polymerase
2015.07.31 View 10496 -
Omnidirectional Free Space Wireless Charging Developed
The simultaneous charging of multiple mobile devices at 0.5 meter away from the power source is now possible under the international electromagnetic field guidelines.
Mobile devices, such as smartphones and laptops, have become indispensable portable items in modern life, but one big challenge remains to fully enjoying these devices: keeping their batteries charged.
A group of researchers at KAIST has developed a wireless-power transfer (WPT) technology that allows mobile devices to be charged at any location and in any direction, even if the devices are away from the power source, just as Wi-Fi works for Internet connections. With this technology, so long as mobile users stay in a designated area where the charging is available, e.g., the Wi-Power zone, the device, without being tethered to a charger, will pick up power automatically, as needed.
The research team led by Professor Chun T. Rim of the Nuclear and Quantum Engineering Department at KAIST has made great strides in WPT development. Their WPT system is capable of charging multiple mobile devices concurrently and with unprecedented freedom in any direction, even while holding the devices in midair or a half meter away from the power source, which is a transmitter. The research result was published in the June 2015 on-line issue of IEEE Transactions on Power Electronics, which is entitled “Six Degrees of Freedom Mobile Inductive Power Transfer by Crossed Dipole Tx (Transmitter) and Rx (Receiver) Coils.”
Professor Rim’s team has successfully showcased the technology on July 7, 2015 at a lab on KAIST’s campus. They used high-frequency magnetic materials in a dipole coil structure to build a thin, flat transmitter (Tx) system shaped in a rectangle with a size of 1m2. Either 30 smartphones with a power capacity of one watt each or 5 laptops with 2.4 watts each can be simultaneously and wirelessly charged at a 50 cm distance from the transmitter with six degrees of freedom, regardless of the devices’ three-axes positions and directions. This means that the device can receive power all around the transmitter in three-dimensional space. The maximum power transfer efficiency for the laptops was 34%. The researchers said that to fabricate plane Tx and Rx coils with the six-degree-of-freedom characteristic was a bottleneck of WPT for mobile applications.
Dipole Coil Resonance System (DCRS)
The research team used the Dipole Coil Resonance System (DCRS) to induce magnetic fields, which was developed by the team in 2014 for inductive power transfer over an extended distance. The DCRS is composed of two (transmitting and receiving) magnetic dipole coils, placed in parallel, with each coil having a ferrite core and connected with a resonant capacitor. Comparing to a conventional loop coil, the dipole coil is very compact and has a less dimension. Therefore, a crossed dipole structure has 2-dimension rather than 3-dimension of a crossed loop coil structure. The DCRS has a great advantage to transfer power even when the resonance frequency changes in the range of 1% (Q factor is below 100). The ferrite cores are optimally designed to reduce the core volume by half, and their ability to transfer power is nearly unaffected by human bodies or surrounding metal objects, making DCRS ideal to transmit wireless power in emergency situations. In a test conducted in 2014, Professor Rim succeeded in transferring 209 watts of power wirelessly to the distance of five meters. (See KAIST’s press release on DCRS for details: http://www.eurekalert.org/pub_releases/2014-04/tkai-wpt041714.php.)
Greater Flexibility and Safer Charging
The research team rearranged the two dipole coils from a parallel position to cross them in order to generate rotating magnetic fields, which was embedded in the Tx’s flat platform. This has made it possible for mobile devices to receive power from any direction.
Although wireless-power technology has been applied to smartphones, it could not offer any substantial advantages over traditional wired charging because the devices still require close contact with the transmitter, a charging pad. To use the devices freely and safely, including in public spaces, the WPT technology should provide mobile users with six degrees of freedom at a distance. Until now, all wireless-charging technologies have had difficulties with the problem of short charging distance, mostly less than 10 cm, as well as charging conditions that the devices should be placed in a fixed position. For example, the Galaxy S6 could only be charged wirelessly in a fixed position, having one degree of freedom. The degree of freedom represents mobile devices’ freedom of movement in three-dimensional space.
In addition, the DCRS works at a low magnetic field environment. Based on the magnetic flux shielding technology developed by the research team, the level of magnetic flux is below the safety level of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guideline (27µT) for general public exposure to electromagnetic field (EMF).
Professor Rim said, “Our transmitter system is safe for humans and compatible with other electronic devices. We have solved three major issues of short charging distance, the dependence on charging directions, and plane coil structures of both Tx and Rx, which have blocked the commercialization of WPT.”
Currently, the research team and KAIST’s spin-off company, TESLAS, Inc., have been conducting pilot projects to apply DCRS in various places such as cafes and offices.
YouTube Link: https://www.youtube.com/watch?v=JU64pMyJioc
Demonstration of 30 Watts Range Omnidirectional Wireless-charging at a Laboratory on KAIST’s Campus
Figure 1: Wide-range omnidirectional wireless-charging system based on DCRS can charge multiple numbers of mobile devices simultaneously in a 1m3 range. The above is a transmitter, and the below is a Samsung Galaxy Note with a receiver embedded inside.
Figure 2: Demonstration of the omnidirectional wireless-charging system (clockwise from top of the left, robust charging despite the presence of metal obstacles, omnidirectional charging, long distance charging, and multiple devices charging)
2015.07.08 View 17056 -
3D Plasmon Antenna Capable of Focusing Light into Few Nanometers
Professors Myung-Ki Kim and Yong-Hee Lee, both of the Physics Department at KAIST, and their research teams have developed a three dimensional (3D) gap-plasmon antenna which can focus light into a space a few nanometers wide. Their research findings were published in the June 10th issue of Nano Letters.
Focusing light into a point-like space is an active research field with many applications. However, concentrating light into a smaller space than its wavelength is often hindered by diffraction. To tackle this problem, many researchers have utilized the plasmonic phenomenon of a metal where light can be confined to a greater extent by overcoming the diffraction limit.
Many researchers have focused on developing a two dimensional (2D) plasmon antenna and were able to focus a light under 5 nanometers wide. However, this 2D antenna revealed a challenge: the light disperses to the opposite end regardless of how small its beam was focused. To solve this difficulty, a 3D structure had to be employed to maximize the light's intensity.
Adopting the proximal focused-ion-beam milling technology, the KAIST research team developed a 3D four nanometer wide gap-plasmon antenna. By squeezing the photons into a 3D nano space of 4 x 10 x 10 nm3 size, the researchers were able to increase the intensity of light by 400,000 times stronger than that of the incident light. Capitalizing on the enhanced intensity of light within the antenna, they intensified the second-harmonic signal and verified that the light was focused in the nano gap by scanning cathodoluminescent images.
The researchers anticipate that this technology will improve the speed of data transfer and processing up to the level of a terahertz (one trillion times per second) and to enlarge the storage volume per unit area on hard disks by 100 times. In addition, high definition images of submolecule size can be taken with actual light, instead of with an electron microscope, while improving the semiconductor process to a smaller size of few nanometers.
Professor Kim said, “A simple yet ingenious idea has shifted the research paradigm from 2D gap-plasmon antennas to 3D antennas. This technology will see numerous applications including in the field of information technology, data storage, imaging medical science, and semiconductor processes.”
The research was sponsored by the National Research Foundation of Korea.
Figure 1: 3D Gap-Plasmon Antenna Structure and Simulation Results
Figure 2 – Constructed 3D Gap-Plasmon Antenna Structure
Figure 3 – Amplified Second Harmonic Signal Generation and Light Focused in the Nano Gap
2015.06.24 View 10472 -
KAIST Team Develops Flexible PRAM
Phase change random access memory (PRAM) is one of the strongest candidates for next-generation nonvolatile memory for flexible and wearable electronics. In order to be used as a core memory for flexible devices, the most important issue is reducing high operating current. The effective solution is to decrease cell size in sub-micron region as in commercialized conventional PRAM. However, the scaling to nano-dimension on flexible substrates is extremely difficult due to soft nature and photolithographic limits on plastics, thus practical flexible PRAM has not been realized yet.
Recently, a team led by Professors Keon Jae Lee and Yeon Sik Jung of the Department of Materials Science and Engineering at KAIST has developed the first flexible PRAM enabled by self-assembled block copolymer (BCP) silica nanostructures with an ultralow current operation (below one quarter of conventional PRAM without BCP) on plastic substrates. BCP is the mixture of two different polymer materials, which can easily create self-ordered arrays of sub-20 nm features through simple spin-coating and plasma treatments. BCP silica nanostructures successfully lowered the contact area by localizing the volume change of phase-change materials and thus resulted in significant power reduction. Furthermore, the ultrathin silicon-based diodes were integrated with phase-change memories (PCM) to suppress the inter-cell interference, which demonstrated random access capability for flexible and wearable electronics. Their work was published in the March issue of ACS Nano: "Flexible One Diode-One Phase Change Memory Array Enabled by Block Copolymer Self-Assembly."
Another way to achieve ultralow-powered PRAM is to utilize self-structured conductive filaments (CF) instead of the resistor-type conventional heater. The self-structured CF nanoheater originated from unipolar memristor can generate strong heat toward phase-change materials due to high current density through the nanofilament. This ground-breaking methodology shows that sub-10 nm filament heater, without using expensive and non-compatible nanolithography, achieved nanoscale switching volume of phase change materials, resulted in the PCM writing current of below 20 uA, the lowest value among top-down PCM devices. This achievement was published in the June online issue of ACS Nano: "Self-Structured Conductive Filament Nanoheater for Chalcogenide Phase Transition." In addition, due to self-structured low-power technology compatible to plastics, the research team has recently succeeded in fabricating a flexible PRAM on wearable substrates.
Professor Lee said, "The demonstration of low power PRAM on plastics is one of the most important issues for next-generation wearable and flexible non-volatile memory. Our innovative and simple methodology represents the strong potential for commercializing flexible PRAM."
In addition, he wrote a review paper regarding the nanotechnology-based electronic devices in the June online issue of Advanced Materials entitled "Performance Enhancement of Electronic and Energy Devices via Block Copolymer Self-Assembly."
Picture Caption:
Low-power nonvolatile PRAM for flexible and wearable memories enabled by (a) self-assembled BCP silica nanostructures and (b) self-structured conductive filament nanoheater.
2015.06.15 View 15411