Mikami Hideharu
| Research Institute for Electronic Science Biology and Life Sciences | Professor |
■Researcher basic information
Profile Information
After completing a Ph.D. in Physics at the Graduate School of Science, The University of Tokyo in 2006, I worked as a researcher at Hitachi, Ltd. During this period, I also served as a visiting researcher at the University of California, Irvine (Nov. 2012 – Nov. 2013). I subsequently joined the Department of Chemistry, Graduate School of Science, The University of Tokyo as an Assistant Professor, and in June 2020 I was appointed Professor at the Research Institute for Electronic Science, Hokkaido University. I also served as a JST PRESTO researcher (2017–2021) and have been a JST CREST principal investigator since 2022.
My research expertise spans optical physics and applied photonics. My past work includes quantum optics and quantum information science, optical disk and optical communication technologies, nonlinear optical microscopy for biological observation (two-photon, SHG, CARS), and high-speed fluorescence microscopy. Currently, my research aims to pioneer the fusion of optical science, information science, and life science.
Researchmap personal page
J-Global ID
Research Field
Educational Organization
- Master's degree program, Graduate School of Information Science and Technology
- Doctoral (PhD) degree program, Graduate School of Information Science and Technology
■Career
Career
- Jun. 2020 - Present
Hokkaido University, Research Institute for Electronic Science, 教授 - Dec. 2014 - May 2020
The University of Tokyo, Graduate School of Science, 助教 - Apr. 2006 - Nov. 2014
Hitachi, Ltd., Central Research Laboratory - Nov. 2012 - Nov. 2013
University of California, Irvine, Department of Chemistry, Assistant Specialist
Educational Background
■Research activity information
Papers
- Compact, widely tunable ultrashort burst pulse generator using four mirrors
Rikako Tanaka, Keitaro Shimada, Ayumu Ishijima, Etsuko Kobayashi, Hideharu Mikami, Ichiro Sakuma, Keiichi Nakagawa
Optics Letters, 50, 9, 2906, 2906, Optica Publishing Group, 24 Apr. 2025
Scientific journal, Ultrashort burst laser pulses serve as powerful tools for precise laser processing, broadband ultrafast spectroscopy, and high-speed laser-scanning microscopy. However, the performance of conventional burst pulse generators is limited by constraints in the pulse time interval variability, pulse energy variability, pulse number variability, and overall system complexity. Here, we present a compact burst pulse generator that offers a broad tuning range for pulse time intervals, along with control over the number of pulses and pulse energies within the burst. It consists of four mirrors, two of which are parallel to each other, and outputs pulses that are equally spaced both temporally and spatially. We demonstrated the generation of a burst laser pulse by shaping a single ultrashort laser pulse into six pulses with time intervals ranging from femtoseconds to nanoseconds. The pulse time intervals and energies were consistent with theoretical results. - High-throughput fluorescence lifetime imaging flow cytometry.
Hiroshi Kanno, Kotaro Hiramatsu, Hideharu Mikami, Atsushi Nakayashiki, Shota Yamashita, Arata Nagai, Kohki Okabe, Fan Li, Fei Yin, Keita Tominaga, Omer Faruk Bicer, Ryohei Noma, Bahareh Kiani, Olga Efa, Martin Büscher, Tetsuichi Wazawa, Masahiro Sonoshita, Hirofumi Shintaku, Takeharu Nagai, Sigurd Braun, Jessica P Houston, Sherif Rashad, Kuniyasu Niizuma, Keisuke Goda
Nature communications, 15, 1, 7376, 7376, 04 Sep. 2024, [International Magazine]
English, Scientific journal, Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments. - Large-volume focus control at 10 MHz refresh rate via fast line-scanning amplitude-encoded scattering-assisted holography
Atsushi Shibukawa, Ryota Higuchi, Gookho Song, Hideharu Mikami, Yuki Sudo, Mooseok Jang
Nature Communications, 15, 1, Springer Science and Business Media LLC, 08 Apr. 2024
Scientific journal, Abstract
The capability of focus control has been central to optical technologies that require both high temporal and spatial resolutions. However, existing varifocal lens schemes are commonly limited to the response time on the microsecond timescale and share the fundamental trade-off between the response time and the tuning power. Here, we propose an ultrafast holographic focusing method enabled by translating the speed of a fast 1D beam scanner into the speed of the complex wavefront modulation of a relatively slow 2D spatial light modulator. Using a pair of a digital micromirror device and a resonant scanner, we demonstrate an unprecedented refresh rate of focus control of 31 MHz, which is more than 1,000 times faster than the switching rate of a digital micromirror device. We also show that multiple micrometer-sized focal spots can be independently addressed in a range of over 1 MHz within a large volume of 5 mm × 5 mm × 5.5 mm, validating the superior spatiotemporal characteristics of the proposed technique – high temporal and spatial precision, high tuning power, and random accessibility in a three-dimensional space. The demonstrated scheme offers a new route towards three-dimensional light manipulation in the 100 MHz regime. - Virtual-freezing fluorescence imaging flow cytometry with 5-aminolevulinic acid stimulation and antibody labeling for detecting all forms of circulating tumor cells.
Hiroki Matsumura, Larina Tzu-Wei Shen, Akihiro Isozaki, Hideharu Mikami, Dan Yuan, Taichi Miura, Yuto Kondo, Tomoko Mori, Yoshika Kusumoto, Masako Nishikawa, Atsushi Yasumoto, Aya Ueda, Hiroko Bando, Hisato Hara, Yuhong Liu, Yunjie Deng, Masahiro Sonoshita, Yutaka Yatomi, Keisuke Goda, Satoshi Matsusaka
Lab on a chip, 23, 6, 1561, 1575, 14 Mar. 2023, [International Magazine]
English, Scientific journal, Circulating tumor cells (CTCs) are precursors to cancer metastasis. In blood circulation, they take various forms such as single CTCs, CTC clusters, and CTC-leukocyte clusters, all of which have unique characteristics in terms of physiological function and have been a subject of extensive research in the last several years. Unfortunately, conventional methods are limited in accurately analysing the highly heterogeneous nature of CTCs. Here we present an effective strategy for simultaneously analysing all forms of CTCs in blood by virtual-freezing fluorescence imaging (VIFFI) flow cytometry with 5-aminolevulinic acid (5-ALA) stimulation and antibody labeling. VIFFI is an optomechanical imaging method that virtually freezes the motion of fast-flowing cells on an image sensor to enable high-throughput yet sensitive imaging of every single event. 5-ALA stimulates cancer cells to induce the accumulation of protoporphyrin (PpIX), a red fluorescent substance, making it possible to detect all cancer cells even if they show no expression of the epithelial cell adhesion molecule, a typical CTC biomarker. Although PpIX signals are generally weak, VIFFI flow cytometry can detect them by virtue of its high sensitivity. As a proof-of-principle demonstration of the strategy, we applied cancer cells spiked in blood to the strategy to demonstrate image-based detection and accurate classification of single cancer cells, clusters of cancer cells, and clusters of a cancer cell(s) and a leukocyte(s). To show the clinical utility of our method, we used it to evaluate blood samples of four breast cancer patients and four healthy donors and identified EpCAM-positive PpIX-positive cells in one of the patient samples. Our work paves the way toward the determination of cancer prognosis, the guidance and monitoring of treatment, and the design of antitumor strategies for cancer patients. - Deep imaging flow cytometry.
Kangrui Huang, Hiroki Matsumura, Yaqi Zhao, Maik Herbig, Dan Yuan, Yohei Mineharu, Jeffrey Harmon, Justin Findinier, Mai Yamagishi, Shinsuke Ohnuki, Nao Nitta, Arthur R Grossman, Yoshikazu Ohya, Hideharu Mikami, Akihiro Isozaki, Keisuke Goda
Lab on a chip, 22, 5, 876, 889, 01 Mar. 2022, [International Magazine]
English, Scientific journal, Imaging flow cytometry (IFC) has become a powerful tool for diverse biomedical applications by virtue of its ability to image single cells in a high-throughput manner. However, there remains a challenge posed by the fundamental trade-off between throughput, sensitivity, and spatial resolution. Here we present deep-learning-enhanced imaging flow cytometry (dIFC) that circumvents this trade-off by implementing an image restoration algorithm on a virtual-freezing fluorescence imaging (VIFFI) flow cytometry platform, enabling higher throughput without sacrificing sensitivity and spatial resolution. A key component of dIFC is a high-resolution (HR) image generator that synthesizes "virtual" HR images from the corresponding low-resolution (LR) images acquired with a low-magnification lens (10×/0.4-NA). For IFC, a low-magnification lens is favorable because of reduced image blur of cells flowing at a higher speed, which allows higher throughput. We trained and developed the HR image generator with an architecture containing two generative adversarial networks (GANs). Furthermore, we developed dIFC as a method by combining the trained generator and IFC. We characterized dIFC using Chlamydomonas reinhardtii cell images, fluorescence in situ hybridization (FISH) images of Jurkat cells, and Saccharomyces cerevisiae (budding yeast) cell images, showing high similarities of dIFC images to images obtained with a high-magnification lens (40×/0.95-NA), at a high flow speed of 2 m s-1. We lastly employed dIFC to show enhancements in the accuracy of FISH-spot counting and neck-width measurement of budding yeast cells. These results pave the way for statistical analysis of cells with high-dimensional spatial information. - AI on a chip.
Akihiro Isozaki, Jeffrey Harmon, Yuqi Zhou, Shuai Li, Yuta Nakagawa, Mika Hayashi, Hideharu Mikami, Cheng Lei, Keisuke Goda
Lab on a chip, 20, 17, 3074, 3090, 26 Aug. 2020, [International Magazine]
English, Scientific journal, Artificial intelligence (AI) has dramatically changed the landscape of science, industry, defence, and medicine in the last several years. Supported by considerably enhanced computational power and cloud storage, the field of AI has shifted from mostly theoretical studies in the discipline of computer science to diverse real-life applications such as drug design, material discovery, speech recognition, self-driving cars, advertising, finance, medical imaging, and astronomical observation, where AI-produced outcomes have been proven to be comparable or even superior to the performance of human experts. In these applications, what is essentially important for the development of AI is the data needed for machine learning. Despite its prominent importance, the very first process of the AI development, namely data collection and data preparation, is typically the most laborious task and is often a limiting factor of constructing functional AI algorithms. Lab-on-a-chip technology, in particular microfluidics, is a powerful platform for both the construction and implementation of AI in a large-scale, cost-effective, high-throughput, automated, and multiplexed manner, thereby overcoming the above bottleneck. On this platform, high-throughput imaging is a critical tool as it can generate high-content information (e.g., size, shape, structure, composition, interaction) of objects on a large scale. High-throughput imaging can also be paired with sorting and DNA/RNA sequencing to conduct a massive survey of phenotype-genotype relations whose data is too complex to analyze with traditional computational tools, but is analyzable with the power of AI. In addition to its function as a data provider, lab-on-a-chip technology can also be employed to implement the developed AI for accurate identification, characterization, classification, and prediction of objects in mixed, heterogeneous, or unknown samples. In this review article, motivated by the excellent synergy between AI and lab-on-a-chip technology, we outline fundamental elements, recent advances, future challenges, and emerging opportunities of AI with lab-on-a-chip technology or "AI on a chip" for short. - Raman image-activated cell sorting.
Nao Nitta, Takanori Iino, Akihiro Isozaki, Mai Yamagishi, Yasutaka Kitahama, Shinya Sakuma, Yuta Suzuki, Hiroshi Tezuka, Minoru Oikawa, Fumihito Arai, Takuya Asai, Dinghuan Deng, Hideya Fukuzawa, Misa Hase, Tomohisa Hasunuma, Takeshi Hayakawa, Kei Hiraki, Kotaro Hiramatsu, Yu Hoshino, Mary Inaba, Yuki Inoue, Takuro Ito, Masataka Kajikawa, Hiroshi Karakawa, Yusuke Kasai, Yuichi Kato, Hirofumi Kobayashi, Cheng Lei, Satoshi Matsusaka, Hideharu Mikami, Atsuhiro Nakagawa, Keiji Numata, Tadataka Ota, Takeichiro Sekiya, Kiyotaka Shiba, Yoshitaka Shirasaki, Nobutake Suzuki, Shunji Tanaka, Shunnosuke Ueno, Hiroshi Watarai, Takashi Yamano, Masayuki Yazawa, Yusuke Yonamine, Dino Di Carlo, Yoichiroh Hosokawa, Sotaro Uemura, Takeaki Sugimura, Yasuyuki Ozeki, Keisuke Goda
Nature communications, 11, 1, 3452, 3452, 10 Jul. 2020, [International Magazine]
English, Scientific journal, The advent of image-activated cell sorting and imaging-based cell picking has advanced our knowledge and exploitation of biological systems in the last decade. Unfortunately, they generally rely on fluorescent labeling for cellular phenotyping, an indirect measure of the molecular landscape in the cell, which has critical limitations. Here we demonstrate Raman image-activated cell sorting by directly probing chemically specific intracellular molecular vibrations via ultrafast multicolor stimulated Raman scattering (SRS) microscopy for cellular phenotyping. Specifically, the technology enables real-time SRS-image-based sorting of single live cells with a throughput of up to ~100 events per second without the need for fluorescent labeling. To show the broad utility of the technology, we show its applicability to diverse cell types and sizes. The technology is highly versatile and holds promise for numerous applications that are previously difficult or undesirable with fluorescence-based technologies. - Sequentially addressable dielectrophoretic array for high-throughput sorting of large-volume biological compartments.
A Isozaki, Y Nakagawa, M H Loo, Y Shibata, N Tanaka, D L Setyaningrum, J-W Park, Y Shirasaki, H Mikami, D Huang, H Tsoi, C T Riche, T Ota, H Miwa, Y Kanda, T Ito, K Yamada, O Iwata, K Suzuki, S Ohnuki, Y Ohya, Y Kato, T Hasunuma, S Matsusaka, M Yamagishi, M Yazawa, S Uemura, K Nagasawa, H Watarai, D Di Carlo, K Goda
Science advances, 6, 22, eaba6712, eaba6712, American Association for the Advancement of Science (AAAS), May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of Saccharomyces cerevisiae based on their growth rate. - High-speed single-pixel imaging by frequency-time-division multiplexing.
Hiroshi Kanno, Hideharu Mikami, Keisuke Goda
Optics letters, 45, 8, 2339, 2342, 15 Apr. 2020, [International Magazine]
English, Scientific journal, We propose and experimentally demonstrate high-speed single-pixel imaging by integrating frequency-division multiplexing and time-division multiplexing (techniques used widely in telecommunications) and applying the combined technique, namely, frequency-time-division multiplexing (FTDM), to optical imaging. Specifically, FTDM single-pixel imaging uses an array of broadband, spatially distributed, dual-frequency combs (i.e., spatial dual combs) for multidimensional illumination and detects an image-encoded time-domain signal with a single-pixel photodetector in a FTDM manner. As a proof-of-principle demonstration, we use the method to show ultrafast two-color (bright-field and fluorescence) single-pixel microscopy of breast cancer cells at a high frame rate of 32,000 fps and ultrafast image velocimetry of fluorescent particles flowing at a high speed of ${ \gt },{2}\;{\rm m/s}$>2m/s. - Virtual-freezing fluorescence imaging flow cytometry.
Hideharu Mikami, Makoto Kawaguchi, Chun-Jung Huang, Hiroki Matsumura, Takeaki Sugimura, Kangrui Huang, Cheng Lei, Shunnosuke Ueno, Taichi Miura, Takuro Ito, Kazumichi Nagasawa, Takanori Maeno, Hiroshi Watarai, Mai Yamagishi, Sotaro Uemura, Shinsuke Ohnuki, Yoshikazu Ohya, Hiromi Kurokawa, Satoshi Matsusaka, Chia-Wei Sun, Yasuyuki Ozeki, Keisuke Goda
Nature communications, 11, 1, 1162, 1162, 06 Mar. 2020, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, By virtue of the combined merits of flow cytometry and fluorescence microscopy, imaging flow cytometry (IFC) has become an established tool for cell analysis in diverse biomedical fields such as cancer biology, microbiology, immunology, hematology, and stem cell biology. However, the performance and utility of IFC are severely limited by the fundamental trade-off between throughput, sensitivity, and spatial resolution. Here we present an optomechanical imaging method that overcomes the trade-off by virtually freezing the motion of flowing cells on the image sensor to effectively achieve 1000 times longer exposure time for microscopy-grade fluorescence image acquisition. Consequently, it enables high-throughput IFC of single cells at >10,000 cells s-1 without sacrificing sensitivity and spatial resolution. The availability of numerous information-rich fluorescence cell images allows high-dimensional statistical analysis and accurate classification with deep learning, as evidenced by our demonstration of unique applications in hematology and microbiology. - Accurate classification of microalgae by intelligent frequency-division-multiplexed fluorescence imaging flow cytometry
Jeffrey Harmon, Hideharu Mikami, Hiroshi Kanno, Takuro Ito, Keisuke Goda
OSA CONTINUUM, 3, 3, 430, 440, Mar. 2020
English, Scientific journal - Intelligent image-activated cell sorting 2.0
Akihiro Isozaki, Hideharu Mikami, Hiroshi Tezuka, Hiroki Matsumura, Kangrui Huang, Marino Akamine, Kotaro Hiramatsu, Takanori Iino, Takuro Ito, Hiroshi Karakawa, Yusuke Kasai, Yan Li, Yuta Nakagawa, Shinsuke Ohnuki, Tadataka Ota, Yong Qian, Shinya Sakuma, Takeichiro Sekiya, Yoshitaka Shirasaki, Nobutake Suzuki, Ehsen Tayyabi, Tsubasa Wakamiya, Muzhen Xu, Mai Yamagishi, Haochen Yan, Qiang Yu, Sheng Yan, Dan Yuan, Wei Zhang, Yaqi Zhao, Fumihito Arai, Robert E. Campbell, Christophe Danelon, Dino Di Carlo, Kei Hiraki, Yu Hoshino, Yoichiroh Hosokawa, Mary Inaba, Atsuhiro Nakagawa, Yoshikazu Ohya, Minoru Oikawa, Sotaro Uemura, Yasuyuki Ozeki, Takeaki Sugimura, Nao Nitta, Keisuke Goda
Lab on a Chip, 20, 13, 2263, 2273, Royal Society of Chemistry (RSC), 2020, [Peer-reviewed]
Scientific journal,The upgraded version of intelligent image-activated cell sorting (iIACS) has enabled higher-throughput and more sensitive intelligent image-based sorting of single live cells from heterogeneous populations.
- Author Correction: A practical guide to intelligent image-activated cell sorting.
Akihiro Isozaki, Hideharu Mikami, Kotaro Hiramatsu, Shinya Sakuma, Yusuke Kasai, Takanori Iino, Takashi Yamano, Atsushi Yasumoto, Yusuke Oguchi, Nobutake Suzuki, Yoshitaka Shirasaki, Taichiro Endo, Takuro Ito, Kei Hiraki, Makoto Yamada, Satoshi Matsusaka, Takeshi Hayakawa, Hideya Fukuzawa, Yutaka Yatomi, Fumihito Arai, Dino Di Carlo, Atsuhiro Nakagawa, Yu Hoshino, Yoichiroh Hosokawa, Sotaro Uemura, Takeaki Sugimura, Yasuyuki Ozeki, Nao Nitta, Keisuke Goda
Nature protocols, 14, 11, 3273, 3273, Nov. 2019, [Peer-reviewed], [International Magazine]
English, An amendment to this paper has been published and can be accessed via a link at the top of the paper. - A practical guide to intelligent image-activated cell sorting.
Akihiro Isozaki, Hideharu Mikami, Kotaro Hiramatsu, Shinya Sakuma, Yusuke Kasai, Takanori Iino, Takashi Yamano, Atsushi Yasumoto, Yusuke Oguchi, Nobutake Suzuki, Yoshitaka Shirasaki, Taichiro Endo, Takuro Ito, Kei Hiraki, Makoto Yamada, Satoshi Matsusaka, Takeshi Hayakawa, Hideya Fukuzawa, Yutaka Yatomi, Fumihito Arai, Dino Di Carlo, Atsuhiro Nakagawa, Yu Hoshino, Yoichiroh Hosokawa, Sotaro Uemura, Takeaki Sugimura, Yasuyuki Ozeki, Nao Nitta, Keisuke Goda
Nature protocols, 14, 8, 2370, 2415, Aug. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Intelligent image-activated cell sorting (iIACS) is a machine-intelligence technology that performs real-time intelligent image-based sorting of single cells with high throughput. iIACS extends beyond the capabilities of fluorescence-activated cell sorting (FACS) from fluorescence intensity profiles of cells to multidimensional images, thereby enabling high-content sorting of cells or cell clusters with unique spatial chemical and morphological traits. Therefore, iIACS serves as an integral part of holistic single-cell analysis by enabling direct links between population-level analysis (flow cytometry), cell-level analysis (microscopy), and gene-level analysis (sequencing). Specifically, iIACS is based on a seamless integration of high-throughput cell microscopy (e.g., multicolor fluorescence imaging, bright-field imaging), cell focusing, cell sorting, and deep learning on a hybrid software-hardware data management infrastructure, enabling real-time automated operation for data acquisition, data processing, intelligent decision making, and actuation. Here, we provide a practical guide to iIACS that describes how to design, build, characterize, and use an iIACS machine. The guide includes the consideration of several important design parameters, such as throughput, sensitivity, dynamic range, image quality, sort purity, and sort yield; the development and integration of optical, microfluidic, electrical, computational, and mechanical components; and the characterization and practical usage of the integrated system. Assuming that all components are readily available, a team of several researchers experienced in optics, electronics, digital signal processing, microfluidics, mechatronics, and flow cytometry can complete this protocol in ~3 months. - Intelligent image-activated cell sorting and beyond
Yasuyuki Ozeki, Nao Nitta, Takeaki Sugimura, Akihiro Isozaki, Hideharu Mikami, Dino Di Carlo, Yoichiroh Hosokawa, Sotaro Uemura, Keisuke Goda
Optics InfoBase Conference Papers, 2019, OSA - The Optical Society, 2019
English, International conference proceedings - Simple, stable, compact implementation of frequency-division-multiplexed microscopy by inline interferometry
Hiroshi Kanno, Hideharu Mikami, Yasin Kaya, Yasuyuki Ozeki, Keisuke Goda
Optics Letters, 44, 3, 467, 470, 2019, [Peer-reviewed]
English, Scientific journal - High-Speed Imaging Meets Single-Cell Analysis
Hideharu Mikami, Cheng Lei, Nao Nitta, Takeaki Sugimura, Takuro Ito, Yasuyuki Ozeki, Keisuke Goda
CHEM, 4, 10, 2278, 2300, Oct. 2018
English - Intelligent Image-Activated Cell Sorting.
Nao Nitta, Takeaki Sugimura, Akihiro Isozaki, Hideharu Mikami, Kei Hiraki, Shinya Sakuma, Takanori Iino, Fumihito Arai, Taichiro Endo, Yasuhiro Fujiwaki, Hideya Fukuzawa, Misa Hase, Takeshi Hayakawa, Kotaro Hiramatsu, Yu Hoshino, Mary Inaba, Takuro Ito, Hiroshi Karakawa, Yusuke Kasai, Kenichi Koizumi, SangWook Lee, Cheng Lei, Ming Li, Takanori Maeno, Satoshi Matsusaka, Daichi Murakami, Atsuhiro Nakagawa, Yusuke Oguchi, Minoru Oikawa, Tadataka Ota, Kiyotaka Shiba, Hirofumi Shintaku, Yoshitaka Shirasaki, Kanako Suga, Yuta Suzuki, Nobutake Suzuki, Yo Tanaka, Hiroshi Tezuka, Chihana Toyokawa, Yaxiaer Yalikun, Makoto Yamada, Mai Yamagishi, Takashi Yamano, Atsushi Yasumoto, Yutaka Yatomi, Masayuki Yazawa, Dino Di Carlo, Yoichiroh Hosokawa, Sotaro Uemura, Yasuyuki Ozeki, Keisuke Goda
Cell, 175, 1, 266, 276, 20 Sep. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal - High-throughput imaging flow cytometry by optofluidic time-stretch microscopy
Lei Cheng, Kobayashi Hirofumi, Wu Yi, Li Ming, Isozaki Akihiro, Yasumoto Atsushi, Mikami Hideharu, Ito Takuro, Nitta Nao, Sugimura Takeaki, Yamada Makoto, Yatomi Yutaka, Di Carlo Dino, Ozeki Yasuyuki, Goda Keisuke
NATURE PROTOCOLS, 13, 7, 1603, 1631, Jul. 2018, [Peer-reviewed]
English, Scientific journal - On-chip light-sheet fluorescence imaging flow cytometry at a high flow speed of 1 m/s
Miura Taichi, Mikami Hideharu, Isozaki Akihiro, Ito Takuro, Ozeki Yasuyuki, Goda Keisuke
BIOMEDICAL OPTICS EXPRESS, 9, 7, 3424, 3433, 01 Jul. 2018, [Peer-reviewed]
English, Scientific journal - Ultrafast confocal fluorescence microscopy beyond the fluorescence lifetime limit
Hideharu Mikami, Jeffrey Harmon, Hirofumi Kobayashi, Syed Hamad, Yisen Wang, Osamu Iwata, Kengo Suzuki, Takuro Ito, Yuri Aisaka, Natsumaro Kutsuna, Kazumichi Nagasawa, Hiroshi Watarai, Yasuyuki Ozeki, Keisuke Goda
Optica, 5, 2, 117, 126, 20 Feb. 2018, [Peer-reviewed]
English, Scientific journal - High-speed bioimaging with frequency-division-multiplexed fluorescence confocal microscopy
Hideharu Mikami, Jeffrey Harmon, Yasuyuki Ozeki, Keisuke Goda
Proceedings of SPIE - The International Society for Optical Engineering, 10251, 2017, [Peer-reviewed]
English, International conference proceedings - Rapid mesoscale multiphoton microscopy of human skin
Mihaela Balu, Hideharu Mikami, Jue Hou, Eric O. Potma, Bruce J. Tromberg
BIOMEDICAL OPTICS EXPRESS, 7, 11, 4375, 4387, Nov. 2016, [Peer-reviewed]
English, Scientific journal - Ultrafast optical imaging technology: principles and applications of emerging methods
Hideharu Mikami, Liang Gao, Keisuke Goda
NANOPHOTONICS, 5, 4, 497, 509, Oct. 2016, [Peer-reviewed]
English - Ultrafast optical imaging technology: Principles and applications of emerging methods
Hideharu Mikami, Liang Gao, Keisuke Goda
Nanophotonics, 5, 4, 441, 453, Walter de Gruyter GmbH, 01 Sep. 2016, [Peer-reviewed]
English, Scientific journal - Large field of view multiphoton microscopy of human skin
Mihaela Balu, Hideharu Mikami, Jue Hou, Eric O. Potma, Bruce J. Tromberg
Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 9712, SPIE, 2016, [Peer-reviewed]
English, International conference proceedings - Large field of view multiphoton microscopy of human skin
Mihaela Balu, Hideharu Mikami, Jue Hou, Eric O. Potma, Bruce J. Tromberg
MULTIPHOTON MICROSCOPY IN THE BIOMEDICAL SCIENCES XVI, 9712, 2016, [Peer-reviewed]
English, International conference proceedings - Enhanced speed in fluorescence imaging using beat frequency multiplexing
Hideharu Mikami, Hirofumi Kobayashi, Yisen Wang, Syed Hamad, Yasuyuki Ozeki, Keisuke Goda
HIGH-SPEED BIOMEDICAL IMAGING AND SPECTROSCOPY: TOWARD BIG DATA INSTRUMENTATION AND MANAGEMENT, 9720, 2016, [Peer-reviewed]
English, International conference proceedings - Ultrafast Confocal Fluorescence Microscopy by Frequency-Division-Multiplexed Multi-Line Focusing
Hideharu Mikami, Hirofumi Kobayashi, Syed Hamad, Yasuyuki Ozeki, Keisuke Goda
2016 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO), 2016, [Peer-reviewed]
English, International conference proceedings - Compact and fully collinear light source for broadband multiplex CARS microscopy covering the fingerprint region
Hideharu Mikami, Manabu Shiozawa, Masataka Shirai, Koichi Watanabe
OPTICS EXPRESS, 23, 13, 17217, 17222, Jun. 2015, [Peer-reviewed]
English, Scientific journal - Compact and fully collinear light source for broadband multiplex CARS microscopy covering the fingerprint region
Hideharu Mikami, Manabu Shiozawa, Masataka Shirai, Koichi Watanabe
OPTICS EXPRESS, 23, 13, 17217, 17222, Jun. 2015, [Peer-reviewed]
English, Scientific journal - Compact light source for ultrabroadband coherent anti-Stoke Raman scattering (CARS) microscopy
Hideharu Mikami, Manabu Shiozawa, Masataka Shirai, Koichi Watanabe
OPTICS EXPRESS, 23, 3, 2872, 2878, Feb. 2015, [Peer-reviewed]
English, Scientific journal - Quantitative index of arbitrary molar concentration for coherent anti-Stoke Raman scattering (CARS) spectroscopy and microscopy
Hideharu Mikami, Manabu Shiozawa, Masataka Shirai, Koichi Watanabe
OPTICS EXPRESS, 23, 4, 5300, 5311, Feb. 2015, [Peer-reviewed]
English, Scientific journal - Compact light source for ultrabroadband coherent anti-Stoke Raman scattering (CARS) microscopy
Hideharu Mikami, Manabu Shiozawa, Masataka Shirai, Koichi Watanabe
OPTICS EXPRESS, 23, 3, 2872, 2878, Feb. 2015, [Peer-reviewed]
English, Scientific journal - Quantitative index of arbitrary molar concentration for coherent anti-Stoke Raman scattering (CARS) spectroscopy and microscopy
Hideharu Mikami, Manabu Shiozawa, Masataka Shirai, Koichi Watanabe
OPTICS EXPRESS, 23, 4, 5300, 5311, Feb. 2015, [Peer-reviewed]
English, Scientific journal - Microholographic optical data storage with spatial mode multiplexing
Hideharu Mikami, Koichi Watanabe
Japanese Journal of Applied Physics, 52, 9, Sep. 2013, [Peer-reviewed]
English, Scientific journal - Compact Optical Module of Homodyne Detection
Hideharu Mikami, Takahiro Kurokawa, Koichi Watanabe
JAPANESE JOURNAL OF APPLIED PHYSICS, 51, 8, Aug. 2012, [Peer-reviewed]
English, Scientific journal - Read Data Transfer Rate Estimation in Optical Phase Multilevel Recording
Atsushi Kikukawa, Hideharu Mikami, Tatsuro Ide, Kentaro Osawa, Koichi Watanabe
JAPANESE JOURNAL OF APPLIED PHYSICS, 51, 8, Aug. 2012, [Peer-reviewed]
English, Scientific journal - Experimental Demonstration of Optical Phase Multilevel Recording in Microhologram
Hideharu Mikami, Kentaro Osawa, Eriko Tatsu, Koichi Watanabe
JAPANESE JOURNAL OF APPLIED PHYSICS, 51, 8, Aug. 2012, [Peer-reviewed]
English, Scientific journal - Reduction of Interlayer Crosstalk of Multilayer Optical Disc by Using Phase-Diversity Homodyne Detection
Tatsuro Ide, Kentaro Osawa, Hideharu Mikami, Koichi Watanabe
JAPANESE JOURNAL OF APPLIED PHYSICS, 51, 8, Aug. 2012, [Peer-reviewed]
English, Scientific journal - Analysis of Phase Multilevel Recording on Microholograms
Tatsuro Ide, Hideharu Mikami, Kentaro Osawa, Koichi Watanabe
JAPANESE JOURNAL OF APPLIED PHYSICS, 50, 9, Sep. 2011, [Peer-reviewed]
English, Scientific journal - Ultra-compact optical module of homodyne detection
Hideharu Mikami, Takahiro Kurokawa, Koichi Watanabe
Optics InfoBase Conference Papers, Optical Society of America (OSA), 2011
English, International conference proceedings - Read data transfer rate estimation on optical phase multilevel recording
Atsushi Kikukawa, Hideharu Mikami, Tatsuro Ide, Kentaro Osawa, Koichi Watanabe
Optics InfoBase Conference Papers, Optical Society of America (OSA), 2011
English, International conference proceedings - Homodyne detection for readout signals of optical disc with a high-coherence laser
Kentaro Osawa, Hideharu Mikami, Takahiro Kurokawa, Koichi Watanabe
OPTICAL DATA STORAGE 2010, 7730, 2010, [Peer-reviewed]
English, International conference proceedings - Optical phase multi-level recording in microhologram
Hideharu Mikami, Kentaro Osawa, Koichi Watanabe
OPTICAL DATA STORAGE 2010, 7730, 2010, [Peer-reviewed]
English, International conference proceedings - Amplification of Optical Disk Readout Signals by Homodyne Detection
Hideharu Mikami, Takeshi Shimano, Takahiro Kurokawa, Tatsuro Ide, Jiro Hashizume, Koichi Watanabe, Harukazu Miyamoto
JAPANESE JOURNAL OF APPLIED PHYSICS, 48, 3, Mar. 2009, [Peer-reviewed]
English, Scientific journal - Signal-Readout System for Optical Pickup with Homodyne Detection Scheme
Takahiro Kurokawa, Hideharu Mikami, Hiroyuki Minemura, Tatsuro Ide, Koichi Watanabe, Harukazu Miyamoto
JAPANESE JOURNAL OF APPLIED PHYSICS, 48, 3, Mar. 2009, [Peer-reviewed]
English, Scientific journal - Demonstration of Readout-Signal Quality Improvement by Homodyne Detection
Hideharu Mikami, Takahiro Kurokawa, Koichi Watanabe, Harukazu Miyamoto
2009 OPTICAL DATA STORAGE TOPICAL MEETING, 46, 48, 2009, [Peer-reviewed]
English, International conference proceedings - Remote preparation of qutrit states with biphotons
Hideharu Mikami, Takayoshi Kobayashi
Physical Review A - Atomic, Molecular, and Optical Physics, 75, 2, 22 Feb. 2007, [Peer-reviewed]
English, Scientific journal - Remote preparation of qutrit states with biphotons
Hideharu Mikami, Takayoshi Kobayashi
PHYSICAL REVIEW A, 75, 2, Feb. 2007, [Peer-reviewed]
English, Scientific journal - Single-mode approximation of parametric down-conversion
YM Li, H Mikami, HB Wang, T Kobayashi
PHYSICAL REVIEW A, 72, 6, Dec. 2005, [Peer-reviewed]
English, Scientific journal - New high-efficiency source of a three-photon W state and its full characterization using quantum state tomography
H Mikami, YM Li, K Fukuoka, T Kobayashi
PHYSICAL REVIEW LETTERS, 95, 15, 150404, Oct. 2005, [Peer-reviewed]
English, Scientific journal - Efficient generation of a three-photon W state
Hideharu Mikami, Yongmin Li, K. Fukuoka, Takayoshi Kobayashi
Optics InfoBase Conference Papers, Optical Society of America, 2005
English, International conference proceedings - New high-efficiency source of a three-photon W state and its full characterization using quantum state tomography
Hideharu Mikami, Yongmin Li, Kyosuke Fukuoka, Takayoshi Kobayashi
IQEC, International Quantum Electronics Conference Proceedings, 2005, 1012, 1013, 2005, [Peer-reviewed]
English, International conference proceedings - Generation of the four-photon W state and other multiphoton entangled states using parametric down-conversion
Hideharu Mikami, Yongmin Li, Takayoshi Kobayashi
Physical Review A - Atomic, Molecular, and Optical Physics, 70, 5 A, 1, 52308, Nov. 2004, [Peer-reviewed]
English, Scientific journal - Generation of the four-photon W state and other multiphoton entangled states using parametric down-conversion
H Mikami, YM Li, T Kobayashi
PHYSICAL REVIEW A, 70, 5, Nov. 2004, [Peer-reviewed]
English, Scientific journal
Other Activities and Achievements
- 超高速イメージングで生命科学 (特集 バイオイメージング最前線)
三上 秀治, 雷 诚, 鈴木 祐太, 小関 泰之, 合田 圭介, O plus E : Optics + electronics, 38, 10, 922, 926, Oct. 2016
アドコム・メディア, Japanese
Research Themes
- Advanced Bioimaging Support
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2028
鍋倉 淳一, 根本 知己, 山中 めぐみ, 上野 直人, 真野 昌二, 大浪 修一, 藤森 俊彦, 野中 茂紀, 今村 健志, 平岡 泰, 甲本 真也, 松田 道行, 洲崎 悦生, 稲葉 一男, 菅谷 佑樹, 澤田 和明, 佐藤 良勝, 三上 秀治, 岡田 康志, 大野 伸彦, 安永 卓生, 太田 啓介, 小池 正人, 宮澤 淳夫, 深澤 有吾, 渡辺 雅彦, 豊岡 公徳, 片岡 洋祐, 定藤 規弘, 青木 茂樹, 岡田 直大, 林 拓也, 内田 誠一, 桧垣 匠, 舟橋 啓, 小田 祥久, 木森 義隆
前年度までの新学術領域研究(学術研究支援基盤形成)「先端バイオイメージング支援プラットフォーム(ABiS)」の実績を元に、研究者のニーズを調査し、新たな支援内容も加えた体制を構築し、光学顕微鏡、電子顕微鏡、磁気共鳴機器による画像取得、およびそれらの機器より得られた画像の解析の支援を行った。2022年度は、光学顕微鏡支援として101件、電子顕微鏡支援として45件、磁気共鳴画像支援として17件、画像解析支援として17件行い、トレーニングを14回開催した。
新たな支援活動を行うにあたり、オフィシャルサイトをリニューアルした。新しいオフィシャルサイトでは、各支援内容を紹介する動画の掲載や連携している国際バイオイメージングコンソーシアム(GBI: Global BioImaging)の情報の自動アップデート機能などを実装した。公募の周知活動として、このオフィシャルサイトを随時更新して最新情報を発信するとともに、公募案内のポスターをリニューアルして、大学・研究機関に送付した(1,353部)。また、新しい体制を紹介するためのリーフレットも刷新し、周知活動に用いた。
本年度は、発生生物学会第55回大会、第74回日本細胞生物学会年会、日本植物学会第86回大会、第81回日本癌学会学術総会、第95回日本生化学会大会、第45回日本分子生物学会年会、日本生理学会第100回記念大会、日本薬学会143年会において、ブース出展やランチョンセミナー、シンポジウム共催を行い、大会参加者へ支援概要や応募方法の説明を行った。上記の大会のうち、第81回日本癌学会学術総会、第95回日本生化学会大会、第45回日本分子生物学会年会、日本生理学会第100回記念大会、日本薬学会143年会は、生命科学連携推進協議会のもと、4つのプラットフォームが合同で参加した。
Japan Society for the Promotion of Science, Grant-in-Aid for Transformative Research Areas (platforms for Advanced Technologies and Research Resources), National Institute for Physiological Sciences, 22H04926 - 高速・高次元閉ループ光計測技術の確立と神経科学への応用
戦略的な研究開発の推進 戦略的創造研究推進事業 CREST
2022 - 2027
三上 秀治
従来の大規模計測・解析の限界を打破する新しい新たな実験手法「高速・高次元閉ループ光計測技術」を確立し、次世代のバイオDXに貢献する。先端光学技術およびAI技術を軸とした技術開発を行い、開発した装置をマウスおよび線虫の神経系の研究に適用して従来の実験のアプローチでは現実的な時間内での解析が困難であった神経系の機序解明を目指す。
科学技術振興機構, 北海道大学, Principal investigator - ニューロンレベル脳・人工脳インターフェース
科学研究費助成事業
30 Jun. 2022 - 31 Mar. 2024
三上 秀治
本年度は予備的検討として線虫の頭部ニューロン群の高速3D撮像を行い、取得データに対してオフラインで細胞位置の解析を試みるとともに、光操作のための高速光変調の検討を行った。まず、独自開発した高速ライトシート顕微鏡を用いて線虫の頭部神経の撮像を行うため、明視野画像をもとに線虫頭部を視野中心に固定するトラッキングステージを製作し、高速撮像(毎秒50ボリューム)に耐える追従動作を確認した。次に、高速ライトシート顕微鏡の撮像条件を線虫頭部神経にあわせて調整し、自由行動中の線虫の撮像に十分な速度である毎秒50ボリュームの撮像を行った。取得データを各種画像解析ソフトウエアにより解析し、頭部全ニューロンの8割弱にあたる約150個の神経細胞の検出および追跡が可能であることを確認した。また、リアルタイムに特定のニューロン群を選択的に光操作するための光学システムとして、高速な空間光変調器および多光子励起が可能なフェムト秒パルスレーザーを導入し、特定のニューロンにレーザー光を集光・照射する動作の時定数を詳細に検証した。なお、検証のため、照射対象はCMOSカメラで明視野撮像した蛍光ビーズとした。検証の結果、カメラの撮像から集光までの所要時間は90 ms程度であり、自由行動中の線虫であってもリアルタイムに追従しながら集光・照射できる見込みを得た。加えて、一連の処理の各要素に要した時間も確認しており、特に計算処理に要する部分が支配的であることが確認された。この点については、計算アルゴリズムの高速化および計算ハードウエアの変更による大幅な高速化が見込まれており、現状の2D撮像から3D撮像に拡張する場合においてもリアルタイム動作を実現する見通しを得た。
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 22K19261 - 情報通信技術を応用した光学的大規模膜電位計測法の開拓
科学研究費助成事業
01 Apr. 2021 - 31 Mar. 2024
三上 秀治
本年度は生体試料の計測のための環境構築を行うとともに、多重検出方式の検討を前年度に引き続き行った。生体試料計測としてマウス脳皮質の計測を想定し、マウスの飼育環境や手術から観察までの一連の作業に要する機材の整備を行い、in vivoでの神経活動計測が可能な環境を整備した。加えて、方式検討の基盤となる多光子顕微鏡もマウス観察向けに新規に設計、構築を行い、前年度に構築した装置とあわせて、様々な生体試料を用いた評価基盤が構築できた。多重化方式としては主として時分割多重方式の検討を行い、前年度に検討した周波数分割多重との比較を試みた。基礎的な検討として時分割多重は前年度に用いたものと同じ高速な空間光変調器による集光パターンの逐次的な切り替えにより実装した。このため、時定数の評価に必要な装置の特性は前年度に評価済みのものを用いた。動作確認としては3つの直径10 μmの蛍光ビーズを用い、周波数分割多重の実験と同様に明視野画像の画像処理により特定した各ビーズの座標に逐次的にパルスレーザーを照射し、取得した信号波形から各蛍光の強度を計測することができた。本検討では時分割多重方式のみの実装のため逐次的な検出(ランダムアクセス顕微鏡と呼ばれるものに相当)を行ったことになるが、実際は周波数分割多重等の他方式との組み合わせが可能である。このことを見越して各ビーズあたり1点の測定ではなく、周辺の複数点の測定により蛍光ビーズの座標を検出する動作も併せて試み、1秒あたり1 μmのステップで移動させた蛍光ビーズを(明視野画像の情報を用いることなく)追跡することができた。このような動作は計測対象が移動する場合に有効であり、特に通常の撮像に長時間を要する3次元計測において有効であると見込まれる。
日本学術振興会, 基盤研究(B), 北海道大学, 21H02437 - 生命活動をリアルタイムに追跡する超高速3D蛍光顕微鏡
戦略的な研究開発の推進 戦略的創造研究推進事業 さきがけ
2017 - 2021
三上 秀治
従来よりも数10倍高速な、1,000ボリューム/秒の超高速3D蛍光顕微鏡技術を開発する。これにより、活動する生物をリアルタイムかつ正確に記録し、神経活動をはじめとする様々な生命活動の組織・細胞レベルでの理解に貢献する。
科学技術振興機構, 東京大学, Principal investigator
Industrial Property Rights
- レーザ顕微鏡装置およびフローサイトメーター
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特願2010-092673, 13 Apr. 2010
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特開2012-151574, 09 Aug. 2012
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13 Mar. 2015
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特願2013-160079, 01 Aug. 2013
特開2013-254215, 19 Dec. 2013
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特開2012-185873, 27 Sep. 2012
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07 Feb. 2014
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06 Aug. 2010
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Patent right, 橋爪 滋郎, 三上 秀治, 島野 健, 株式会社日立製作所
特願2007-080452, 27 Mar. 2007
特開2008-243273, 09 Oct. 2008
200903041968313740