Kyohei OkuboTokyo Institute of Technology | TITech · Department of Materials Science and Engineering
Kyohei Okubo
Doctor of Engineering
About
59
Publications
9,758
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355
Citations
Introduction
Assistant Professor at Tokyo Institute of Technology. My research interests are magnetic sensing, photonics, and bioimaging.
Additional affiliations
April 2018 - March 2023
April 2017 - March 2018
Position
- Postdoctoral Researcher
Description
- Nanobio Devices Group. Research Fellowships for Young Scientists Funded by Japan Society for Promotion of Science (JSPS)
September 2014 - December 2014
Education
April 2012 - March 2017
April 2008 - March 2012
Publications
Publications (59)
Arraying individual extracellular vesicles (EVs) on a chip is expected one of the promising approaches for investigating their inherent properties. In this study, we immobilized individual EVs on a surface using a nanopatterned tethering chip-based versatile platform. A microfluidic device was used to ensure soft, reproducible exposure of the EVs o...
The diagnosis of gastrointestinal stromal tumor (GIST) using conventional endoscopy is difficult because submucosal tumor (SMT) lesions like GIST are covered by a mucosal layer. Near-infrared hyperspectral imaging (NIR-HSI) can obtain optical information from deep inside tissues. However, far less progress has been made in the development of techni...
Lipid distribution in the liver provides crucial information for diagnosing the severity of fatty liver and fatty liver-associated liver cancer. Therefore, a noninvasive, label-free, and quantitative modality is eagerly anticipated. We report near-infrared hyperspectral imaging for the quantitative visualization of lipid content in mouse liver base...
Rare-earth-doped nanoparticles (NPs), such as NaGdF4 nanocrystals doped with light-emitting rare earth ions, are promising bimodal probes that allow the integration of over 1000 nm near-infrared (OTN-NIR; NIR-II/III) fluorescence imaging and magnetic resonance imaging (MRI) of live bodies. A precise control of the particle size is the key factor fo...
Fatty acids play various physiological roles owing to their diverse structural characteristics, such as hydrocarbon chain length (HCL) and degree of saturation (DS). Although the distribution of fatty acids in biological tissues is associated with lipid metabolism, in situ imaging tools are still lacking for HCL and DS. Here, we introduce a framewo...
Micelles have been extensively used in biomedicine as potential carriers of hydrophobic fluorescent dyes. Their small diameters can potentially enable them to evade recognition by the reticuloendothelial system, resulting in prolonged circulation. Nevertheless, their lack of stability in physiological environments limits the imaging utility of mice...
Significance:
Determining the extent of gastric cancer (GC) is necessary for evaluating the gastrectomy margin for GC. Additionally, determining the extent of the GC that is not exposed to the mucosal surface remains difficult. However, near-infrared (NIR) can penetrate mucosal tissues highly efficiently.
Aim:
We investigated the ability of near...
We developed a small MRI/NIR-II probe to target HER2 (tetanucleotide) breast cancer cells. The probe is composed of PLGA-b-PEG micelles encapsulated NIR-II, and Gd-DOTA is conjugated at the border of PLGA/PEG. Herceptin was then conjugated to carboxyl residues of PLGA-b-PEG chains. We examined the influence of carboxyl group ratios on the probe pro...
Rare-earth-doped ceramics, which are near-infrared (NIR) fluorescent materials, have applications as photonic materials in various fields, including medical biology. The NIR wavelength range in which these rare-earth-based materials function is highly transparent in biological tissues and is suitable for deep-tissue imaging. However, the most commo...
Multimodal imaging is attractive in biomedical research because it can provide multidimensional information about objects that individual techniques can not accomplish. In particular, combining over one-thousand-nanometer near-infrared (OTN–NIR) fluorescence and magnetic resonance (MR) imaging is promising for detecting lesions with high sensitivit...
We report a computed tomography (CT) technique for mapping near-infrared fluorescence (NIRF) lifetime as a multiplex three-dimensional (3D) imaging method, using a conventional NIR camera. This method is achieved by using a time-gated system composed of a pulsed laser and an NIR camera synchronized with a rotatable sample stage for NIRF-CT imaging....
Organic molecules that emit near-infrared (NIR) fluorescence at wavelengths above 1000 nm, also known as the second NIR (NIR-II) biological window, are expected to be applied to optical in vivo imaging of deep tissues. The study of molecular states of NIR-II dye and its optical properties are important to yield well-controlled fluorescent probes; h...
Multimodal imaging can provide multidimensional information for understanding concealed microstructures or bioprocesses in biological objects. The combination of over-1000 nm near-infrared (OTN-NIR) fluorescence imaging and magnetic resonance (MR) imaging is promising in providing high sensitivity and structural information of lesions. This combina...
Fluorescence imaging in the over-thousand nanometer (OTN-) near-infrared (NIR) wavelength region is an emerging technique for real-time bioimaging. OTN-NIR probe is made from micellar nanoparticles encapsulated IR-1061 dye in the core of poly(ethylene glycol) (PEG) phospholipid (PL), such as 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-N...
Over-thousand-nanometer (OTN) near-infrared (NIR) fluorophores are useful for biological deep imaging because of the reduced absorption and scattering of OTN-NIR light in biological tissues. IR-1061, an OTN-NIR fluorescent dye, has a hydrophobic and cationic backbone in its molecular structure, and a non-polar counter ion, BF4 -. Because of its hyd...
Gastric cancer is one of the most serious cancers that affects and kills many people around the world every year. Early treatment of gastric cancer dramatically improves the survival rate. Endoscopy has become an important tool for early detection. Since invasive gastric cancer or the edge of the invasive gastric cancer is difficult to find by usin...
The refraction of fluorescence from the inside of a sample at the surface results in fluctuations in fluorescence computed tomography (CT). We evaluated the influence of the difference in refractive index (RI) between the sample body and the surroundings on fluorescence CT results. The brightest fluorescent point is away from the correct point on t...
Near infrared (NIR) light offers high transparency in biological tissue. Recent advances in NIR fluorophores including organic dyes and lanthanide-doped inorganic nanoparticles have realized the effective use of the NIR optical window for in vivo bioimaging and photodynamic therapy. The narrow energy level intervals used for electronic transition t...
Trivalent lanthanide ions (Ln3+) have been used as active centers for fluorescence mainly in inorganic crystalline or glassy solids. Ln3+-containing systems allow easier thermal emission with narrower energy gaps under near-infrared light excitation because the Ln3+ electron–phonon interaction is a weak coupling. The multiphonon relaxation theory h...
Rare-earth-doped ceramic nanoparticles (RED-CNPs) have been studied for biological applications because they can convert biopermeable near-infrared light into visible and ultraviolet light. Both the host ceramic and the microenvironment around RED-CNPs may influence their luminescence characteristics; however, the effects of surrounding molecules h...
Near-infrared (NIR) light has been used for in vivo deep imaging in the biomedical field owing to its high permeability in biological tissues. Conventional fluorescence bioimaging requires simultaneous optical excitation, which can induce undesired results such as autofluorescence. In the present study, we report a polymer-based NIR afterglow fluor...
Rare-earth doped ceramics nanoparticles are promising near-infrared fluorescent emitters for ratiometric nanothermometry in biological system. This study investigated the use of polypentaerythritol tetraacrylate as a coating of β-NaYF4:Yb3+,Ho3+,Er3+ nanoparticles to suppress luminescence quenching in water. It was found that upconversion emission...
We designed a biodegradable hybrid nanostructure for near-infrared (NIR)-induced photodynamic therapy (PDT) using an ultrasmall upconversion (UC) phosphor (β-NaYF4:Yb³⁺, Er³⁺ nanoparticle: NPs) and a hydrocarbonized rose bengal (C18RB) dye, a hydrophobized rose bengal (RB) derivative. The UC-NPs were encapsulated along with C18RB in the hydrophobic...
In this study, a laparoscopic imaging device and a light source able to select wavelengths by bandpass filters were developed to perform multispectral imaging (MSI) using over 1000 nm near-infrared (OTN-NIR) on regions under a laparoscope. Subsequently, MSI (wavelengths: 1000–1400 nm) was performed using the built device on nine live mice before an...
Japanese Journal of Optics: Publications of the Optical Society of Japan.
Bending and absorption of light dominate transparency in biological tissue. Refractive index matching is a promising approach to achieve transparency in various organs and tissues. Near-infrared (NIR) light, especially longer than 1000 nm in wavelength, provides an observatio...
This book explains transparency in biology with emphasis on bending and absorption, which together are the essence of transparency. The reader is provided with an understanding of why the interior of the body can be made to appear transparent through the application of elementary physics. Based on the principle of transparency, emerging imaging tec...
Hyperspectral imaging (HSI) is a powerful imaging technique for biomedical applications, such as disease detection, diagnosis, and surgery assistance. HSI provides a three-dimensional dataset (two spatial and one spectral), which allows to obtain spectral curve at each pixel in acquired images. Spectral imaging data offers diagnostic information on...
This study shows the possibility of plaque detection by near-infrared hyper spectrum imaging (NIR-HSI) and machine learning without plaque stain. While the plaque stain shows where the plaque is, the plaque stain leaves color and may cause anaphylaxis. Near-infrared images are obtained from the plaque cultured teeth by NIR-HSI. RGB images of staine...
In this study, we proposed to detect the unstained plaque by using the near infrared hyperspectral image and Artificial Neural Network. The proposed method suggested that invisible plaques could be visualized without staining.
Upconverting erbium(III) complexes in N,N-dimethylformamide (DMF) were prepared via chloride ligand replacement by tetrafluoroborate, as suggested by changes in the spectral profile. Cl − removal as precipitated salts was evidenced by X-ray diffraction (XRD) analysis. The systematic spectroscopic work indicated optimal condition for complex prepara...
Imaging utilizing the near-infrared (NIR) light has attracted numerous attention due to the possibility in the deep tissue penetration as it can overcome the light scattering and absorption of tissue components. The ultraviolet (UV) unlikely penetrates the skin, while the visible (VIS) light can be scattered or absorbed by tissue components. This p...
The field of self-reporting materials is gaining increased attention recently. These materials can convey the forces applied to them without the need to integrate external devices. The ability to report strain exerted onto polymers is especially important, as it might give indication of high levels of force that may damage the material. These mater...
One of the most commonly used near infrared (NIR) dyes is indocyanine green (ICG), which has been extensively used for NIR bioimaging, photothermal and photodynamic therapy. However, upon excitation this dye can react with molecular oxygen to form singlet oxygen (SO), which can then cleave ICG to form non-fluorescent debris. In order to reduce the...
It had been known that the near-infrared is the most transparent optical region. In early 2000’ s, near infrared imaging device came into market for various imaging use as the fruit of fiber optics communication development. Various near-infrared laser diodes are also becoming convenient and inexpensive for easy operation and compact device designs...
Contactless thermal imaging generally relies on mid-infrared cameras and fluorescence imaging with temperature-sensitive phosphors. Fluorescent thermometry in the near-infrared (NIR) region is an emerging technique for analysing deep biological tissues but still requires observation depth calibration. We present an NIR fluorescence time-gated imagi...
A compact photonic sensor using a perforated waveguide (PW) that functions as a bimodal interferometer (BiMI) is developed for affinity sensing. A 2D array of holes is formed on the bimodal region of the waveguide. The PW is designed to allow 1.31 μm wavelength light to transmit, harnessing the strong optical intensity distribution inside the holes...
Indocyanine Green (ICG) is one of the most common fluorescent dyes that emits in the near-infrared (NIR) region, with extensive use in the medical field. However, this dye is susceptible to photobleaching, thermal degradation and oxidation in acidic conditions. The major pathway by which ICG photobleaches involves sensitization to form singlet oxyg...
A trimodal polymer waveguide interferometer was fabricated for bio/chemical sensing. Dual single-mode waveguides were used for the input and output ports to improve coupling efficiency in the trimodal waveguide. The performance of the interferometer was characterized via numerical simulation. Based on the analysis results, the optimum dimensions of...
We present a hybrid nanofabrication technology for realizing single-crystalline metal nanoparticle ensembles, such as trimers, heptamers and periodic arrays; well-suited for nanoplasmonics applications. Top-down engineered nanotemplates result in the deterministic...
Tethering nanoarray chip enables 10^5 exosomes to be immobilized on PEG-lipid based spot array. The size of nanospots fabricated are down to 40 nm diameter, which is equivalent to minimum diameter of exosomes. AFM measurements revealed that the aspect ratio of captured exosomes derived from two different cell-lines (Sk-Br-3 and HEK 239) was signifi...
[Background] Exosomes, one of extracellular vehicles (EVs), have recently attracted much attention as promising biomarkers for an early stage diagnostic test. Exosomes are heterogeneous in size ranging from 30–150 nm in diameter. Quantitative evaluation of single exosome is a challenging issue because the coexistence of several other kinds of EVs i...
Exosomes, one of extracellular vesicles in size ranging from 30–150 nm in diameter, have recently attracted much attention as promising biomarker for an early stage diagnostic test. Here, we propose an assay platform called exosome array on which exosomes are separately immobilized and analyzed in the similar manner as DNA array. Polyethyleneglycol...
A microfabricated directional coupler (DC) was used for the label-free, real-time detection of proteins. As an alternative to biomolecules such as antibodies, molecularly imprinted polymer (MIP) was used. With human serum albumin (HSA) as a model analyte, distinct responses were observed. On the other hand, the sensor did not respond to bovine seru...
Metal nanoparticle (NP) research has made significant progress over the past few decades, and now a wide range of materials with well-controlled size and dispersity are available [1].
Much study in recent years has focused on analysis of single exosomes, where methods and instruments that enable more high-throughput and multiplex assay are still needed. This paper reports an exosome nanoarray platform fabricated by a combination of on-chip nanofabrication and selective chemical modification. The exosome array chip enables indivi...
A silicon nitride directional coupler (DC) used to create a biosensing device is presented. The DC detects changes in the refractive index of the cladding ( n clad ) as changes in the relative output intensity. The DC length ( L ), n clad -dependent sensitivities of the DC, and preferred dimensions of the single-mode DC waveguides are obtained thro...
Autonomous transport and release of bacterial cells by self-propelled micromotors was achieved. The motors consisted of zinc and platinum hemispheres formed on polystyrene beads and moved as a result of simultaneous redox reactions occurring on both metal ends. The highly negative redox potential of zinc enabled the selection of a wide variety of o...
We used silicon nitride (Si3N4) directional coupler (DC) interferometers to fabricate evanescent field biosensors for detection of aptamer hybridization. The DC detects temporal changes in refractive index (RI) as changes in the relative intensities of near-fields. Numerical simulation provided information for sensitivity of the DC as well as prefe...
A microfabricated directional coupler (DC) was used for the detection of DNA conjugated with quantum dots. Output optical signals from DCs of a wide range of device lengths correspond well to theoretical and simulation results. Even 20 µm-long DC devices could detect changes in the output optical intensity by monitoring the near-field pattern using...
Differentiation of several liquids and detection of DNAs conjugated with quantum-dots will be demonstrated using a microfabricated optical directional-coupler (DC)-based biochemical sensor. With DC sensors of different lengths, optical intensities measured at the output ports fit quite well to the corresponding fitting curve and the curve calculate...
We report a bio-photonic sensing system in a g¬apless directional coupler (DC) interferometer. Compared with conventional DCs, the structure was simplified by eliminating a gap between parallel waveguides, reducing device complexity and achieving excellent sensitivity for affinity biosensing. FDTD simulation provided conditions for a single-mode wa...
Solutions in the form of liquid droplets were processed and analyte molecule sensing was performed, based on surface plasmon resonance (SPR). Two types of devices with different microfluidic functions were used. Procedures such as measurement of solution volume, mixing of solutions, and sequential analyses were conducted, followed by SPR sensing. A...
Zinc/platinum (Zn/Pt) bimetallic micromotors have been developed. They moved based on the reduction of fuel compounds such as bromine, p-benzoquinone, and methanol at the surface of the Pt and the oxidation (dissolution) of Zn that occur simultaneously. The redox potential of Zn2+/Zn is very negative and was advantageous to cause the redox reaction...
Questions
Question (1)
I've got a positive tone resist for electron beam lithography, ZEP520A. I need to spin this resist on gold surface to pattern an array of disks ranging from ~50 nm to 300 nm diameter. Generally a resist on metal has some troubles such as weak adhesion, bubbles or cracks after baking or developing. I would like to know any way to make the resist stick enough on gold. I will start with using an adhesion promoter (HMDS) that is spun in advance of ZEP spinning. Please can you give me some advices? Thanks in advance.
-Kyohei
