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Microscopy Approach Poised to Offer New Insights into Liver Diseases
Researchers have developed a new way to visualize the progression of nonalcoholic fatty liver disease (NAFLD) in mouse models of the disease. The new microscopy method provides a high-resolution 3D view that could lead to important new insights into NAFLD, a condition in which too much fat is stored in the liver. “It is estimated that a quarter of the adult global population has NAFLD, yet an effective treatment strategy has not been found,” said professor Pilhan Kim from the Graduate School of Medical Science and Engineering at KAIST. “NAFLD is associated with obesity and type 2 diabetes and can sometimes progress to liver failure in serious case.” In the Optical Society (OSA) journal Biomedical Optics Express, Professor Kim and colleagues reported their new imaging technique and showed that it can be used to observe how tiny droplets of fat, or lipids, accumulate in the liver cells of living mice over time. “It has been challenging to find a treatment strategy for NAFLD because most studies examine excised liver tissue that represents just one timepoint in disease progression,” said Professor Kim. “Our technique can capture details of lipid accumulation over time, providing a highly useful research tool for identifying the multiple parameters that likely contribute to the disease and could be targeted with treatment.” Capturing the dynamics of NAFLD in living mouse models of the disease requires the ability to observe quickly changing interactions of biological components in intact tissue in real-time. To accomplish this, the researchers developed a custom intravital confocal and two-photon microscopy system that acquires images of multiple fluorescent labels at video-rate with cellular resolution. “With video-rate imaging capability, the continuous movement of liver tissue in live mice due to breathing and heart beating could be tracked in real time and precisely compensated,” said Professor Kim. “This provided motion-artifact free high-resolution images of cellular and sub-cellular sized individual lipid droplets.” The key to fast imaging was a polygonal mirror that rotated at more than 240 miles per hour to provide extremely fast laser scanning. The researchers also incorporated four different lasers and four high-sensitivity optical detectors into the setup so that they could acquire multi-color images to capture different color fluorescent probes used to label the lipid droplets and microvasculature in the livers of live mice. “Our approach can capture real-time changes in cell behavior and morphology, vascular structure and function, and the spatiotemporal localization of biological components while directly visualizing of lipid droplet development in NAFLD progression,” said Professor Kim. “It also allows the analysis of the highly complex behaviors of various immune cells as NAFLD progresses.” The researchers demonstrated their approach by using it to observe the development and spatial distribution of lipid droplets in individual mice with NAFLD induced by a methionine and choline-deficient diet. Next, they plan to use it to study how the liver microenvironment changes during NAFLD progression by imaging the same mouse over time. They also want to use their microscope technique to visualize various immune cells and lipid droplets to better understand the complex liver microenvironment in NAFLD progression.
KAIST Develops Core Technology for Ultra-small 3D Image Sensor
(from left: Dr. Jong-Bum Yo, PhD candidate Seong-Hwan Kimand Professor Hyo-Hoon Park) A KAIST research team developed a silicon optical phased array (OPA) chip, which can be a core component for three-dimensional image sensors. This research was co-led by PhD candidate Seong-Hwan Kim and Dr. Jong-Bum You from the National Nanofab Center (NNFC). A 3D image sensor adds distance information to a two-dimensional image, such as a photo, to recognize it as a 3D image. It plays a vital role in various electronics including autonomous vehicles, drones, robots, and facial recognition systems, which require accurate measurement of the distance from objects. Many automobile and drone companies are focusing on developing 3D image sensor systems, based on mechanical light detection and ranging (LiDAR) systems. However, it can only get as small as the size of a fist and has a high possibility of malfunctioning because it employs a mechanical method for laser beam-steering. OPAs have gained a great attention as a key component to implement solid-state LiDAR because it can control the light direction electronically without moving parts. Silicon-based OPAs are small, durable, and can be mass-produced through conventional Si-CMOS processes. However, in the development of OPAs, a big issue has been raised about how to achieve wide beam-steering in transversal and longitudinal directions. In the transversal direction, a wide beam-steering has been implemented, relatively easily, through a thermo-optic or electro-optic control of the phase shifters integrated with a 1D array. But the longitudinal beam-steering has been remaining as a technical challenge since only a narrow steering was possible with the same 1D array by changing the wavelengths of light, which is hard to implement in semiconductor processes. If a light wavelength is changed, characteristics of element devices consisting the OPA can vary, which makes it difficult to control the light direction with reliability as well as to integrate a wavelength-tunable laser on a silicon-based chip. Therefore, it is essential to devise a new structure that can easily adjust the radiated light in both transversal and longitudinal directions. By integrating tunable radiator, instead of tunable laser in a conventional OPA, Professor Hyo-Hoon Park from the School of Electrical Engineering and his team developed an ultra-small, low-power OPA chip that facilitates a wide 2D beam-steering with a monochromatic light source. This OPA structure allows the minimizing of the 3D image sensors, as small as a dragonfly’s eye. According to the team, the OPA can function as a 3D image sensor and also as a wireless transmitter sending the image data to a desired direction, enabling high-quality image data to be freely communicated between electronic devices. Kim said, “It’s not an easy task to integrate a tunable light source in the OPA structures of previous works. We hope our research proposing a tunable radiator makes a big step towards commercializing OPAs.” Dr. You added, “We will be able to support application researches of 3D image sensors, especially for facial recognition with smartphones and augmented reality services. We will try to prepare a processing platform in NNFC that provides core technologies of the 3D image sensor fabrication.” This research was published in Optics Letters on January 15. Figure 1.The manufactured OPA chip Figure 2. Schematic feature showing an application of the OPA to a 3D image sensor
Next-Generation Holographic Microscope for 3D Live Cell Imaging
KAIST researchers have developed a revolutionary bio-medical imaging tool, the HT-1, to view and analyze cells, which is commercially available. Professor YongKeun Park of the Physics Department at KAIST and his research team have developed a powerful method for 3D imaging of live cells without staining. The researchers announced the launch of their new microscopic tool, the holotomography (HT)-1, to the global marketplace through a Korean start-up that Professor Park co-founded, TomoCube (www.tomocube.com). Professor Park is a leading researcher in the field of biophotonics and has dedicated much of his research career to working on digital holographic microscopy technology. He collaborated with TomoCube’s R&D team to develop a state-of-the-art, 2D/3D/4D holographic microscope that would allow a real-time label-free visualization of biological cells and tissues. The HT is an optical analogy of X-ray computed tomography (CT). Both X-ray CT and HT share the same physical principle—the inverse of wave scattering. The difference is that HT uses laser illumination whereas X-ray CT uses X-ray beams. From the measurement of multiple 2D holograms of a cell, coupled with various angles of laser illuminations, the 3D refractive index (RI) distribution of the cell can be reconstructed. The reconstructed 3D RI map provides structural and chemical information of the cell including mass, morphology, protein concentration, and dynamics of the cellular membrane. The HT enables users to quantitatively and non-invasively investigate the intrinsic properties of biological cells, for example, dry mass and protein concentration. Some of the research team’s breakthroughs that have leveraged HT’s unique and special capabilities can be found in several recent publications, including a lead article on the simultaneous 3D visualization and position tracking of optically trapped particles which was published in Optica on April 20, 2015. Current fluorescence confocal microscopy techniques require the use of exogenous labeling agents to render high-contrast molecular information. Therefore, drawbacks include possible photo-bleaching, photo-toxicity, and interference with normal molecular activities. Immune or stem cells that need to be reinjected into the body are considered particularly difficult to employ with fluorescence microscopy. “As one of the two currently available, high-resolution tomographic microscopes in the world, I believe that the HT-1 is the best in class regarding specifications and functionality. Users can see 3D/4D live images of cells, without fixing, coating or staining cells. Sample preparation times are reduced from a few days or hours to just a few minutes,” said Professor Park. Two Korean hospitals, Seoul National University Hospital in Bundang and Boramae Hospital in Seoul, are using this microscope currently. The research team has also introduced the HT-1 at the Photonics West Exhibition 2016 that took place on February 16-18 in San Francisco, USA. Professor Park added, “Our technology has set a new paradigm for cell observation under a microscope. I expect that this tomographic microscopy will be more widely used in future in various areas of pharmaceuticals, neuroscience, immunology, hematology, and cell biology.” Figure 1: HT-1 and Its Specifications Figure 2: 3D Images of Representative Biological Cells Taken with the HT-1
The First Winner of Sang Soo Lee Award in Optics and Photonics
The Optical Society of Korea and the Optical Society of America selected Mario Garavaglia, a researcher at the La Plata Optical Research Center in Argentina, as the first winner of the Sang Soo Lee Award. Dr. Garavaglia has been selected to receive the award in recognition for his research and education in the field of optics and photonics in Argentina. The Sang Soo Lee Award, co-established by the Optical Society of Korea and the Optical Society of America in 2012, is awarded to an individual who has made a significant impact in the field. Special considerations are made for individuals who have introduced a new field of research, helped establish a new industry, or made a great contribution to education in the field. The award is sponsored by the late Doctor Sang Soo Lee's family, the Optical Society of Korea, and the Optical Society of America. The late Doctor Sang Soo Lee (1925~2010) has been widely known as the 'father of optics' in Korea. He was an active educator, researcher, and writer. Dr. Lee served as the first director of the Korea Advanced Institute of Science (KAIS), the predecessor to KAIST, which was Korea's first research oriented university. Dr. Lee also served as the 6th president of KAIST between 1989 to 1991 and was a KAIST professor of physics for 21 years. He oversaw the completion of 50 Ph.D. and 100 Master's students as well as published 230 research papers. Philip Bucksbaum, the president of the Optical Society of America, commented, "Garavaglia has been an example to the spirit of the Sang Soo Lee Award. The award is the recognition for his tireless efforts and commitment to the development of optics and photonics in Argentina through his teaching, research, and publications." Jeong-Won Woo, the president of the Optical Society of Korea, said, "The Sang Soo Lee Award is given to researchers who have consistently contributed to the development of the field. Garavaglia is a well respected researcher in Argentina, and we are truly happy with his selection." Dr. Garavaglia established a spectroscopy, optic, and laser laboratory in Universidad Nacional de La Plata in 1966. He founded the Center for Optical Research in 1977 and served as the chief of the laboratory until 1991. Dr. Garavaglia published over 250 research papers in the fields of classical optics, modern optics, photoemission spectroscopy, and laser spectroscopy. He has also received the Galileo Galilei Award from the International Commission for Optics in 1999.
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