研究者詳細 - 尾上　弘晃

論文 - 尾上　弘晃

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MECHANICALLY-SENSITIVITY-TUNABLE STRUCTURAL-COLOR CHEMICAL SENSOR COMBINED WITH DNA-APTAMER HYDROGEL FOR VISIBLE SILVER ION DETECTION

Ueno R., Yamawaki S., Onoe H.

MicroTAS 2022 - 26th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2022 - 26th International Conference on Miniaturized Systems for Chemistry and Life Sciences） 1071 - 1072 2022年

This paper describes an eye-recognizable structural-color hydrogel chemical sensor that can mechanically adjust its sensitivity. In our system, the Ag+-ion-responsive DNA-aptamer hydrogel and structural-color hydrogel are patterned between two substrates. We built the working theory of our sensor based on mechanics of material and plotted the sensitivity characteristics with respect to its design parameters: the geometric designs and the Young's moduli of the hydrogels. To examine this theory, we fabricated the sensor device and its sensitivity to Ag+ ions showed good agreement with the theoretical calculation derived from material of mechanics.

MEGAHELTZ-BAND ULTRASOUND-TRIGGERED ON-DEMAND DRUG RELEASE FROM HYDROGEL MICROSPHERES WITH ACOUSTIC-RESPONSIVE MICROBUBBLES

Takatsuka S., Kubota T., Kurashina Y., Onoe H.

This paper reports MHz-band ultrasound (US)-triggered on-demand drug release from alginate hydrogel microspheres with release promoting microbubbles (MBs). As a drug carrier, calcium alginate (Ca-Alg.) hydrogel microspheres were centrifugally fabricated by ejecting a mixed pre-gel solution composed of sodium alginate (Na-Alg.), fluorescent polystyrene nanoparticle (fluor-PS-NPs) (drug model) and MBs to CaCl2 solution to form ionically cross-linked instantly. The MBs were vibrated and crushed by MHz-US irradiation that is non-harmful to human and frequently used in practical clinical scene. Therefore, MBs can improve the US-response of microspheres. The encapsulated MBs promoted the release of the drug by US. Therefore, this US-triggered system can be an effective on-demand drug delivery system (DDS) because of its ability of precise controlled drug release.

Multiphoton Photoreduction for Biomimetic Applications of Hydrogels

Nagano Y., Tsunemitsu K., Onoe H., Terakawa M.

2022 Conference on Lasers and Electro-Optics Pacific Rim, CLEO-PR 2022 - Proceedings （2022 Conference on Lasers and Electro-Optics Pacific Rim, CLEO-PR 2022 - Proceedings） 2022年

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Multiphoton Photoreduction for Biomimetic Applications of Hydrogels

Nagano Y., Tsunemitsu K., Onoe H., Terakawa M.

Optics InfoBase Conference Papers （Optics InfoBase Conference Papers） 2022年

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OIL-SEALED HYDROGEL MICROWELL ARRAY FOR ANALYSIS ON SECRETORY COMPONENTS FROM CONFINED SINGLE CELLS

Yamagata C., Itai S., Kurashina Y., Asai M., Hoshino A., Onoe H.

We proposed an oil-sealed hydrogel microwell array for analysis of secretory components from isolated single cells. The purpose of our device is to realize the isolation of the secretory components during cell culture by combining the semi-permeable arginine-glycine-aspartate (RGD)-modified calcium alginate microwell and the oil sealing. We demonstrated the oil-sealing property, the impermeability to extracellular vesicles (EVs) or growth factor proteins (GFs), and the permeability to nutrients of our device by using three types of fluorescent particles with different diameters. We believe that our oil-sealed hydrogel microwell array will contribute to biomedical analysis on single-cell metabolism that helps to understand the mechanisms of various diseases.

PERMEATION CHARACTERISTIC OF EXOSOME-ENCAPSULATING MICRO-HYDROGEL

Takeuchi D., Takatsuka S., Hamazaki Y., Kurashina Y., Hoshino A., Onoe H.

This paper describes exosome-encapsulating micro-hydrogels that enable diffusion-driven release of exosomes (Figure 1). The exosome-encapsulating micro-hydrogels were fabricated (i) by micromolding and (ii) by ejecting exosome-containing pre-gel solution with a centrifugal microfluidic device. We confirmed the permeation characteristics of exosomes by using two types of gels, calcium alginate, and barium alginate whose pore sizes are smaller than the exosome size (30-150 nm). We confirmed that ~25% of the encapsulated exosomes were successfully released from the exosome-encapsulating micro-hydrogels for 4 days, indicating that alginate-based micro-hydrogel could be used for therapeutic system capable of release of exosomes.

UNIDIRECTIONAL ANALYSIS OF CARDIAC PROPAGATION VELOCITY BY HUMAN IPSC-DERIVED CARDIAC CORE-SHELL MICROFIBER

Masuda A., Itai S., Kurashina Y., Tohyama S., Onoe H.

We propose a simple and quantitative assessment of cardiac maturation by calcium propagation velocity. A microfiber-shaped cardiac tissue enables the uniform orientation of cardiomyocyte along the fiber direction, allowing the easy calculation of propagation velocities by one-way-transmission of signals over a long distance. We evaluated the maturation of our microfiber tissues by electrical stimulation and detected 26% increase in the propagation velocity comparing to the immature tissue. Our system of maturity assessment would contribute to the construction of matured cardiac model as a platform for elucidating the pathology of cardiac diseases and drug effects.

Microfabrication of cellulose nanofiber-reinforced hydrogel by multiphoton polymerization

Sugiyama H., Tsunemitsu K., Onoe H., Obata K., Sugioka K., Terakawa M.

Scientific Reports （Scientific Reports） 11 （ 1 ） 2021年12月

The mechanical strength of hydrogel microstructures is crucial for obtaining the desired flexibility, robustness, and biocompatibility for various applications such as cell scaffolds and soft microrobots. In this study, we demonstrate the fabrication of microstructures composed of cellulose nanofibers (CNFs) and poly(ethylene glycol) diacrylate (PEGDA) hydrogels by multiphoton polymerization. The stress of the fabricated microstructure during tensile testing increased with an increase in the CNF concentration, indicating that the mechanical strength of the microstructure was enhanced by using CNFs as fillers. Moreover, the swelling ratio of the microstructure increased with increasing CNF concentration in the PEGDA hydrogel. Our results show the potential of the technique for the microfabrication of advanced cell scaffolds and soft microrobots with the desired mechanical strength.

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Janus hydrogel microbeads for glucose sensing with ph calibration

Ando M., Tsuchiya M., Itai S., Murayama T., Kurashina Y., Heo Y.J., Onoe H.

Sensors （Sensors） 21 （ 14 ） 2021年07月

ISSN 14248220

We present fluorescent Janus hydrogel microbeads for continuous glucose sensing with pH calibration. The Janus hydrogel microbeads, that consist of fluorescent glucose and pH sensors, were fabricated with a UV-assisted centrifugal microfluidic device. The microbead can calibrate the pH values of its surroundings and enables accurate measurements of glucose within various pH condi-tions. As a proof of concept, we succeeded in obtaining the accurate value of glucose concentration in a body-fluid-like sample solution. We believe that our fluorescent microbeads, with pH calibration capability, could be applied to fully implantable sensors for continuous glucose monitoring.

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Analysis on Internal Biomolcular Network Structure of ATP-Drive Actomyosin-Collagen Hybrid Actuator

Kohno K., Hiratsuka Y., Onoe H.

21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021 （21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021） 651 - 654 2021年06月

We investigated the relationship between the deformation of the molecular network of myosin and actin and the macroscopic actuator contraction. Although several bioactuators using actomyosin have been reported in the past, the relationship between the molecular-scale structure and the motion of actomyosin actuators remains largely unexplored. We stained for actin, myosin, and collagen, respectively, and observed the internal biomolecular structure of the actuator by fluorescence observation. We took time-lapse images of the contraction of fluorescently stained actuators and determined the molecular contraction ratio of actomyosin. Finally, the macro and micro contraction ratios of the actuators were compared and examined to understand the internal mechanism of the actomyosin-collagen bioactuator.

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Stimuli-Responsive Structural-Color Hydrogel Chemical Sensor Microarray with Separated Functional Structures

Ueno R., Yamawaki S., Onoe H.

This paper describes an eye-recognizable stimuli-responsive structural-color hydrogel chemical sensor microarray having independent functional structures. Single unit of this microarrayed sensor is separated into two functional parts: a stimuli-responsive part and a structural-color part, enabling visible color sensing for various types of target molecules. In order to demonstrate our concept, we fabricated ethanol and Ag+ ions responsive microarrayed sensors with l00-m-scale units and observed their color change in response to these chemical targets. We believe that our sensor could be applied to continuous environmental monitoring such as water quality, and widen the range of materials for stimuli responsive structural color hydrogel sensors.

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Split-Ring-Shaped Biodegradable pH Sensor for Wireless and Battery-Free Monitoring of Agricultural Fields

Hori K., Inami A., Kan T., Onoe H.

This paper describes a pH sensor for soil monitoring that is composed of fully biodegradable materials in the soil. Our biodegradable pH sensor is composed of only two key elements: One is a magnesium electromagnetic antenna that dissolves in water, and the other is a protection layer of hydroxyapatite that decomposes in response to pH. This sensor works as an electromagnetic split-ring resonator (metamaterial) that reflects electromagnetic waves with specific frequency in GHz band, enabling in wireless remote sensing without any electric circuits or batteries. We demonstrated wireless pH detection of soil for aiming to realize an environmentally friendly monitoring sensor that does not require collection after installation.

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Near Infrared Light-Triggerd on-Demand Drug Delivery from Non-Toxic Hydrogel Microbeads with Heat Transducer

Takatsuka S., Kubota T., Kurashina Y., Onoe H.

This paper describes a near-infrared (NIR) light-triggered drug release system using alginate hydrogel microbeads. As a drug carrier, calcium alginate hydrogel microbeads encapsulating heat transducing particle (Fe304 particles) were fabricated by a centrifugal based fabrication method. The Fe304 particles instantly generate heat due to localized surface plasmon resonance when irradiated with NIR light. As a result, the calcium alginate hydrogel is thermally denatured to release a drug model. By irradiating NIR-laser to the hydrogel microbeads, we confirmed the release of fluorescent polystyrene particles ( 10 nm) as a drug model. This result indicates that the polymer network of the calcium alginate hydrogel responded to the heat at the molecular scale, even though calcium alginate hydrogel is generally stable to heat. This NIR light-triggered drug release system using Fe3O4 particles would be an effectiveand safe platform for on-demand drug delivery.

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Endothelial Chemical Reaction and Drug Test Reproduced on Molded Flexible Collagen Hydrogel Tube

Itai S., Onoe H.

We reproduce chemical reactions of blood vessels by a flexibly deformable collagen tube device. The device is composed of an unfixed collagen hydrogel tube, enabling the reproduction of both macro and micro scale deformation of the vessel tissue. In addition, the device is easily perfused because the collagen hydrogel tube is directly attached to silicone tubes. We succeeded in demonstrating the chemical deformation of vessel tissue and endothelial cells by inflammatory mediators. Moreover, the drug testing was presented by anti-inflammatory chemicals. We believe that our flexible culturing device could help the construction of functional blood vessels reproducing in vivo chemical reactions in high similarity, and contribute to biomedical researches and pharmacokinetic testing.

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Ultrasound-triggered on-demand drug delivery using hydrogel microbeads with release enhancer

Kubota T., Kurashina Y., Zhao J.Y., Ando K., Onoe H.

Materials and Design （Materials and Design） 203 2021年05月

ISSN 02641275

Ultrasound-triggered drug delivery has been widely researched for its potential to improve the therapeutic efficacy of drugs. This paper presents drug release using hydrogel microbeads with release enhancer for efficient ultrasound-triggered drug delivery. By using a centrifuge-based microfluidic device, drug-model-encapsulating calcium alginate hydrogel microbeads containing tungsten particles with high acoustic impedance were fabricated. Because the tungsten particles work as release enhancer, the hydrogel microbeads become to have high sensitivity to ultrasound with localized variation in acoustic impedance so that the release rate of drug models improves. By applying ultrasound at 20 kHz to the hydrogel microbeads, the release of fluorescent silica nanoparticles that are a drug model for virus vectors, micelles, and proteins was tested. Importantly, the proposed hydrogel microbeads released the drug model even under a cavitation-suppressed environment. Furthermore, the additional coating on the hydrogel microbeads with poly-L-lysine enabled us to adjust the release rate of the drug model. The proposed ultrasound-triggered drug release system using release enhancer is expected to be an effective approach for expanding the varieties of applicable treatments using on-demand drug delivery systems.

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Shape-recognizable origami sheet device with single walled carbon nanotube strain sensor

Mori T., Onoe H.

Journal of Microelectromechanical Systems （Journal of Microelectromechanical Systems） 30 （ 2 ） 234 - 242 2021年04月

ISSN 10577157

This article describes a shape-recognizable sheet device using origami structures with single-walled carbon nanotubes (SWCNTs) strain sensors. Recently, a sheet-like measurement system that is directly attached to an object has been attracting attention for obtaining the shape, motion, and deformation of the object as alternative systems with external cameras. However, previous sheet-like measurement systems are difficult to distinguish between the stretch and the bend of the object appropriately. Here we propose a sheet-like measurement system that can distinguish the stretch and the bend individually by using origami structures. We formed a strain sensor using SWCNTs that was deposited on a substrate to form a 5-7 nm thin film. By patterning the SWCNTs strain sensors, origami-based sheet devices were fabricated. We confirmed that our origami sheet device obtained the bending and stretching information separately by attaching the device to cylinders. We believe that the origami system could contribute to the observation of complex deformations such as artificial skin, human interface, and biomedical applications. [2020-0324]

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Simultaneous crosslinking induces macroscopically phase-separated microgel from a homogeneous mixture of multiple polymers

Kurashina Y., Tsuchiya M., Sakai A., Maeda T., Heo Y.J., Rossi F., Choi N., Yanagisawa M., Onoe H.

Applied Materials Today （Applied Materials Today） 22 2021年03月

This paper reports a unique phase separation behavior, a simultaneous-crosslinking-driven phase separation in co-gelation (SPSiC) core–shell microgel that spontaneously forms from a homogeneous pre-gel solution of multiple polymers. The SPSiC microgel, composed of an alginate shell and an N-isopropylacrylamide (NIPAM) core, were synthesized by a single fabrication step wherein a mixed pre-gel solution of sodium alginate and NIPAM monomer was ejected by centrifugation with photo-polymerization and ion crosslinking instantaneously. Phase separation was modeled by varying the degree of polymerization and the size of the polymer chain. Moreover, an implantable, multi-functional drug delivery system combined with a transdermal glucose sensor was demonstrated with core–shell Janus SPSiC microgels. This work shows a macroscopic phase separation behavior, which occurs during the gelation process, and also provides a simple and unique methodology to create multifunctional bio-microprobes.

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Deformation Simulation of Soft Spiral-Shaped Hydrogel Swimmers for Autonomous Swimming Control

Yoshida K., Onoe H.

Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS) （Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)） 2021-January 736 - 739 2021年01月

ISSN 9781665419123

Many of these microorganisms can change the morphology of their spiral-shaped flagella to control their motility. By mimicking these flagella system, soft spiral-shaped microswimmers for autonomous swimming controlled have been proposed. By patterning the stimuli-responsive hydrogel, the geometry of the microswimmer changes in response to the external stimuli, and thus the swimming velocity is also changed. However, a more detailed analysis of geometry change is essential for the determination of the suitable design and accurate propulsion control. Therefore, we analyzed the deformation behavior in detail. We revealed that the pattern angle is an important parameter for acceleration/deceleration of the microswimmer.

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Ultrasound-Triggered Drug Release from Hydrogel Microspheres with Release Booster

Kubota T., Kurashina Y., Onoe H.

ISSN 9781665419123

This paper describes ultrasound-triggered drug release from hydrogel microspheres with release booster. As a drug carrier, calcium alginate hydrogel microspheres containing drug model and tungsten particles were fabricated by using a centrifugal microfluidic device. The tungsten particles with high acoustic impedance enable the hydrogel microspheres to have high sensitivity to ultrasound so that the release rate of the drug models improves. By applying ultrasound to the hydrogel microspheres, we confirmed the release of fluorescent silica nanoparticles and protein as a drug model. Importantly, the drug model was released from our hydrogel microspheres even in a cavitation-suppressed environment, indicating that this system could reduce the damage to tissues. Our proposed ultrasound-triggered drug release system using tungsten particles would be an effective on-demand drug delivery system (DDS).

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Shape-Measurable Device Based on Origami Structure with Single Walled Carbon Nanotube Strain Sensor

Mori T., Onoe H.

ISSN 9781665419123

This paper describes a shape-measurable sheet device using origami structures with single-walled carbon nanotubes (SWCNTs) strain sensors. Previous measurement systems tended to be unable to recognize the stretching and bending of the object surface as different deformation. Here, we propose a shape-measurable device based on origami structure that can distinguish the stretching and the bending appropriately using only strain sensors. We fabricated the strain sensors using SWCNTs that was formed a 5-7 nm thin film on a substrate. We experimented that our origami sheet device could recognize the bending and stretching information separately by attaching the device to cylinders. We are convinced that the origami sheet system could contribute to the observation of complex deformations in various fields.

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尾上 弘晃

論文 - 尾上 弘晃

尾上　弘晃

論文 - 尾上　弘晃