論文 - 尾上　弘晃

Adeno-Associated Virus-Encapsulated Alginate Microspheres Loaded in Collagen Gel Carriers for Localized Gene Transfer

Kurashina Y., Kurihara S., Kubota T., Takatsuka S., Hirabayashi M., Shimmura H., Miyahara H., Hioki A., Matsushita Y., Muramatsu J., Ogawa Y., Fujioka M., Okano H.J., Onoe H.

Advanced Healthcare Materials （Advanced Healthcare Materials）  13 （ 12 ）  2024年05月

ISSN  21922640

　概要を見る

This work reports localized in vivo gene transfer by biodegradation of the adeno-associated virus-encapsulating alginate microspheres (AAV-AMs) loaded in collagen gel carriers. AAV-AMs are centrifugally synthesized by ejecting a mixed pre-gel solution of alginate and AAV to CaCl2 solution to form an ionically cross-linked hydrogel microsphere immediately. The AAV-AMs are able to preserve the AAV without diffusing out even after spreading them on the cells, and the AAV is released and transfected by the degradation of the alginate microsphere. In addition, AAV-AMs can be stored by cryopreservation until use. By implanting this highly convenient AAV-encapsulated hydrogel, AAV-AMs can be loaded into collagen gel carriers to fix the position of the implanted AAV-AMs and achieve localized gene transfer in vivo. In vivo experiments show that the AAV-AMs loaded in collagen gel carriers are demonstrated to release the encapsulated AAV for gene transfer in the buttocks muscles of mice. While conventional injections caused gene transfer to the entire surrounding tissue, the biodegradation of AAV-AMs shows that gene transfer is achieved locally to the muscles. This means that the proposed AAV-loaded system is shown to be a superior method for selective gene transfer.

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Light-Triggered Transmittance Control in Thermoresponsive Hydrogels by Femtosecond Laser Direct Writing

Kashikawa K., Tomikawa H., Onoe H., Terakawa M.

ACS Applied Optical Materials （ACS Applied Optical Materials）  2 （ 4 ） 565 - 573 2024年04月

　概要を見る

Thermoresponsive hydrogels, which exhibit changes in their optical properties and volume due to temperature variations, are promising candidates for applications in soft devices. In this study, we demonstrate the modulation of transmittance in a thermoresponsive hydrogel through light stimulation employing gold microstructures fabricated via multiphoton photoreduction. The spatial integration of photoresponsiveness, attributed to high-density gold nanoparticles within the thermoresponsive hydrogel, was accomplished through the high-speed laser scanning of femtosecond laser pulses. The temperature measurement during the fabrication of the gold microstructure revealed that the high-speed and multiple scanning over the same path effectively reduced the temperature in the irradiated area of femtosecond laser pulses. The present approach enabled the mitigation of thermal effects during the fabrication, resulting in minimizing distortion in the fine lines of the structures. Upon exposure to stimulus light, a rapid change in the transmittance of the region where the structures were fabricated was prominently observed. The present method unveils a promising avenue for the advancement of light-responsive soft devices.

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In-line micro-spectrometer with a structural color polymer filter for the color and concentration monitoring system

Nishita S., Onoe H.

Sensors and Actuators A: Physical （Sensors and Actuators A: Physical）  367 2024年03月

ISSN  09244247

　概要を見る

Monitoring systems for color and concentration of liquids have an important role in improving the fabrication process stably, not only in pipelines but also in microchannels. Our suggested in-line micro-spectrometer with an elastic structural color filter has detectability for color and concentration changes with a 40-mm size. The sequence of our device is the following: (1) the elastic structural color filter splits the white light from an LED, (2) the split light transmits the sample liquid, and (3) a photodiode receives the transmitted light. The structural color polymer is mechanically compressed inside the micro-spectrometer, leading to fixing the optical path even though the light wavelength is changed continuously. We fabricated the elastic structural color polymer with 200 nm silica nanoparticles and PEGPEA (poly- (ethylene glycol) phenyl ether acrylate). The prototype of the in-line micro-spectrometer with a red (λ = 596 nm) filter showed the detectability of the difference between yellow and green dyes. Moreover, the micro-spectrometer successfully distinguished the concentration of green-dyed water. This proposed in-line micro-spectrometer would contribute to developing in-line microfluidic color monitoring systems for biochemical analyses and material production.

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Mucin-Layer-Secreting in Vitro Intestinal Tube-Shaped Device with Cryptic Structure for Bacterial Co-Culture

Uramoto S., Tanaka S., Itai S., 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)）     485 - 488 2024年

ISSN  10846999

　概要を見る

We propose an in vitro intestinal tube-shaped device with a secreted mucin layer that enables us to achieve stable and continuous co-culturing with bacteria. Our tube-shaped device is made of collagen hydrogel and has 3D crypt-like structures created by electrolytically generated microbubbles. Bacterial suspension can be perfused via glass/silicone tubes attached at both ends of the tube device. Supply of culture medium diffused from the outside of the tube ensures a stable culture of Caco-2 and HT29 cells on the inside of the tube. We confirmed that HT29 cells mainly secreted a mucin layer in the apical portion of cryptic structures that spatially separates the intestinal cells and bacteria as seen in vivo environments. As a result, the co-culture of intestinal cells and lactobacillus in vitro was demonstrated in the 3D crypt-like structures in our intestinal tube-shaped device.

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Entirely Biodegradable Wireless pH Sensor with Split-Ring Resonators for Soil pH Monitoring

Sakabe K., Kan T., Onoe H.

Advanced Materials Technologies （Advanced Materials Technologies）  2024年

　概要を見る

This paper describes a wireless and battery-free soil pH sensor made entirely of degradable materials. Soil pH monitoring is significant for precision agriculture and environmental conservation because soil health can be estimated by measuring soil pH. Soil pH can be measured by collecting soil samples and analyzing them in a laboratory environment or by inserting an electrode-type sensor into the soil and measuring soil pH on site. However, neither method is suitable for wide-area soil pH sensing for precision agriculture or environmental conservation. Herein, a fully biodegradable wireless pH sensor is presented that can be dispersed to outdoor environment to detect soil acidity. The sensor is operated wirelessly through split-ring resonators (SRRs) that consist of patterned octacalcium phosphate (OCP)-coated magnesium (Mg) on a poly-lactic acid (PLA) sheet. At acidic soil pH, the degradation of each SRR results in a change in the electromagnetic response of the sensor. The operation of the sensor in six different types of acidic soils is demonstrated to distinguish the acidic soil wirelessly. It is expected that the biodegradable sensor can be applied to low-cost, easy-to-use, and environmentally friendly monitoring of soil pH.

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Electromagnetic Metamaterial Absorbers for Soil Property Evaluation

Sato S., Sakabe K., Onoe H., Kan T.

Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS) （Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)）     999 - 1002 2024年

ISSN  10846999

　概要を見る

In this paper, we proposed a sensor probe utilizing an electromagnetic metamaterial absorber. This device comprises a tri-layer structure with periodically arranged copper split-ring resonators, a resin layer, and a magnesium layer, forming a complete electromagnetic wave absorber. Magnesium in contact with the soil dissolves in response to soil properties, and wireless measurement of the reflected response due to dissolution enables measurement of soil properties. Simulation and reflection measurement results revealed that this device can absorb 70% of incident electromagnetic waves. Furthermore, we examined the relationship between the reflection spectrum and the polarization direction, as well as the correlation between the time of device placement on soil and the reflection spectrum. The results showed that the device exhibited a low dependency on polarization direction and underwent significant changes in the reflection spectrum with the dissolution of magnesium. Therefore, this device shows a promising potential for a practical application in soil property evaluation.

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Dual-Sensing Mechanical Hydrogel Biosensor Composed by Aptamer Recognition and DNA Logic Gates

Kato S., Takinoue M., 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)）     322 - 325 2024年

ISSN  10846999

　概要を見る

This paper presents a hydrogel biosensor that can simultaneously sense the co-existence of two substances through mechanical response using aptamer molecular recognition and DNA logic gates. Mechanical response is a preferable property in hydrogel sensors, so we have created a swelling hydrogel biosensor and have also added logical processing abilities to widen the applications of the sensor. We demonstrated the biosensor's ability against two targets, caffeine and theophylline, by measuring the swelling ratio of the hydrogel. We believe that our proposed hydrogel biosensor can be applied to many MEMS and μTAS applications because of its mechanical responsiveness and programmable reactions.

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Collagen Hollow Microbeads for Engineered Hollow Organ Model in Vitro

Abeta S., Masuda A., Hioki A., Shoji 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)）     477 - 480 2024年

ISSN  10846999

　概要を見る

We propose an in vitro model to mimic the hollow structure of biological tissues (e.g. heart or stomach) using hollow core-shell collagen microgel beads. By using collagen hydrogel as the shell of the microbeads, cells encapsulated inside of the collagen shell can proliferate and form a tissue structure with a hollow center. In this paper, as a first step toward engineered hollow structure tissue formation, we report a fabrication method for core-shell (hollow) alginate microgel beads by a simple droplet-dipping method using a two-layer coaxial nozzle device. To apply collagen hydrogel to this droplet-dipping method, we applied alginate cross-linking network as a template for creating collagen microgel beads and dissolved the alginate network after the collagen hydrogel was stabilized. By combining these techniques, we believe that hollow collagen microgel beads encapsulating cells can easily and massively be produced for reconstructing in vitro hollow organ models.

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Macroscale Collagen-Actomyosin Hybrid Actuator Built from Bioderived Materials

Yoshida K., Kohno K., Hiratsuka Y., Onoe H.

Advanced Functional Materials （Advanced Functional Materials）  33 （ 51 ）  2023年12月

ISSN  1616301X

　概要を見る

Biological muscles mainly consist of motor proteins that play essential roles and have a hierarchical structure covered with collagen that can transmit the tension to bones via tendons. The artificial reconstruction of motor proteins is highly expected from the viewpoint of engineering and biology. Although artificial muscles have been developed via synthetic and biological molecular motors, there is a considerable gap between the components of artificial and biological muscles, resulting in a significant obstacle to further scale-up and force transfer through macroscale structures. To overcome these obstacles via bioderived biomolecules, this study proposes a collagen-actomyosin hybrid soft actuator inspired by the structure of biological muscles. Collagen gel entrapping actomyosin can play roles in maintaining the actuator's shape and transmitting the tensile force. The generated forces reach the micro-newton range, enabling the actuation of millimeter-scale mechanical components. These properties may be helpful for the fabrication of soft robotic systems with advanced functionalities.

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Hydrogel-Sheathed hiPSC-Derived Heart Microtissue Enables Anchor-Free Contractile Force Measurement

Kurashina Y., Fukada K., Itai S., Akizuki S., Sato R., Masuda A., Tani H., Fujita J., Fukuda K., Tohyama S., Onoe H.

Advanced Science （Advanced Science）  10 （ 35 ）  2023年12月

　概要を見る

In vitro reconstruction of highly mature engineered heart tissues (EHTs) is attempted for the selection of cardiotoxic drugs suitable for individual patients before administration. Mechanical contractile force generated in the EHTs is known to be a critical indicator for evaluating the EHT response. However, measuring contractile force requires anchoring the EHT in a tailored force-sensing cell culture chamber, causing technical difficulties in the stable evaluation of contractile force in long-term culture. This paper proposes a hydrogel-sheathed human induced pluripotent stem cell (hiPSC)-derived heart microtissue (H3M) that can provide an anchor-free contractile force measurement platform in commonly used multi-well plates. The contractile force associated with tissue formation and drug response is calculated by motion tracking and finite element analysis on the bending angle of the hydrogel sheath. From the experiment of the drug response, H3M is an excellent drug screening platform with high sensitivity and early testing capability compared to conventionally anchored EHT. This unique platform would be useful and versatile for regenerative therapy and drug discovery research in EHT.

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Schwann cell-encapsulated chitosan-collagen hydrogel nerve conduit promotes peripheral nerve regeneration in rodent sciatic nerve defect models

Takeya H., Itai S., Kimura H., Kurashina Y., Amemiya T., Nagoshi N., Iwamoto T., Sato K., Shibata S., Matsumoto M., Onoe H., Nakamura M.

Scientific Reports （Scientific Reports）  13 （ 1 ）  2023年12月

　概要を見る

Chitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN−), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN− and silicone+ groups. Meanwhile, the CCN− and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects.

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Spatiotemporal single-cell tracking analysis in 3D tissues to reveal heterogeneous cellular response to mechanical stimuli

Kasahara K., Muramatsu J., Kurashina Y., Miura S., Miyata S., Onoe H.

Science Advances （Science Advances）  9 （ 41 ）  2023年10月

　概要を見る

Mechanical stimuli have been recognized as important for tissue maturation, homeostasis and constructing engineered three-dimensional (3D) tissues. However, we know little about the cellular mechanical response in tissues that could be considerably heterogeneous and spatiotemporally dynamic due to the complex structure of tissues. Here, we report a spatiotemporal single-cell tracking analysis of in vitro 3D tissues under mechanical stretch, to reveal the heterogeneous cellular behavior by using a developed stretch and optical live imaging system. The system could affect the cellular orientation and directly measure the distance of cells in in vitro 3D myoblast tissues (3DMTs) at the single-cell level. Moreover, we observed the spatiotemporal heterogeneous cellular locomotion and shape changes under mechanical stretch in 3DMTs. This single-cell tracking analysis can become a principal method to investigate the heterogeneous cellular response in tissues and provide insights that conventional analyses have not yet offered.

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Spatially-selective enhancement of mechanical strength through localized cross-linking of double network hydrogels

Tsunemitsu K., Watanabe A., Onoe H., Terakawa M.

Optical Materials Express （Optical Materials Express）  13 （ 10 ） 2914 - 2924 2023年10月

　概要を見る

To advance the development of flexible materials for soft robotics applications, it is crucial to enhance the elastic modulus and breaking the stress of soft materials, such as hydrogels. Double network hydrogels (DN gels) have displayed remarkable mechanical strength owing to their unique network structure composed of two types of polymer networks. However, current fabrication methods for DN gels entail cross-linking two distinct hydrogel polymers throughout the entire hydrogel matrix. In this study, we focused on employing multi-photon polymerization (MPP) with femtosecond laser pulses as a cross-linking method for hydrogels to achieve spatially selective formation of DN gel structures at the micrometer scale, along with the consequent improvement in local mechanical strength. We assessed the mechanical properties of the fabricated structures and confirmed that the mechanical strength varied within the regions where DN gel was locally formed.

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Unusual Selective Monitoring of N,N-Dimethylformamide in a Two-Dimensional Material Field-Effect Transistor

Fukui A., Matsuyama K., Onoe H., Itai S., Ikeno H., Hiraoka S., Hiura K., Hijikata Y., Pirillo J., Nagata T., Takei K., Yoshimura T., Fujimura N., Kiriya D.

ACS Nano （ACS Nano）  17 （ 15 ） 14981 - 14989 2023年08月

ISSN  19360851

　概要を見る

N,N-Dimethylformamide (DMF) is an essential solvent in industries and pharmaceutics. Its market size range was estimated to be 2 billion U.S. dollars in 2022. Monitoring DMF in solution environments in real time is significant because of its toxicity. However, DMF is not a redox-active molecule; therefore, selective monitoring of DMF in solutions, especially in polar aqueous solutions, in real time is extremely difficult. In this paper, we propose a selective DMF sensor using a molybdenum disulfide (MoS2) field-effect transistor (FET). The sensor responds to DMF molecules but not to similar molecules of formamide, N,N-diethylformamide, and N,N-dimethylacetamide. The plausible atomic mechanism is the oxygen substitution sites on MoS2, on which the DMF molecule shows an exceptional orientation. The thin structure of MoS2-FET can be incorporated into a microfluidic chamber, which leads to DMF monitoring in real time by exchanging solutions subsequently. The designed device shows DMF monitoring in NaCl ionic solutions from 1 to 200 μL/mL. This work proposes the concept of selectively monitoring redox-inactive molecules based on the nonideal atomic affinity site on the surface of two-dimensional semiconductors.

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Controlled release of adeno-associated virus from alginate hydrogel microbeads with enhanced sensitivity to ultrasound

Takatsuka S., Kubota T., Kurashina Y., Kurihara S., Hirabayashi M., Fujioka M., Okano H.J., Onoe H.

Biotechnology and Bioengineering （Biotechnology and Bioengineering）  120 （ 8 ） 2371 - 2377 2023年08月

ISSN  00063592

　概要を見る

Adeno-associated virus (AAV)-based gene therapy holds promise as a fundamental treatment for genetic disorders. For clinical applications, it is necessary to control AAV release timing to avoid an immune response to AAV. Here we propose an ultrasound (US)-triggered on-demand AAV release system using alginate hydrogel microbeads (AHMs) with a release enhancer. By using a centrifuge-based microdroplet shooting device, the AHMs encapsulating AAV with tungsten microparticles (W-MPs) are fabricated. Since W-MPs work as release enhancers, the AHMs have high sensitivity to the US with localized variation in acoustic impedance for improving the release of AAV. Furthermore, AHMs were coated with poly-l-lysine (PLL) to adjust the release of AAV. By applying US to the AAV encapsulating AHMs with W-MPs, the AAV was released on demand, and gene transfection to cells by AAV was confirmed without loss of AAV activity. This proposed US-triggered AAV release system expands methodological possibilities in gene therapy.

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L-2L ladder digital-to-analogue converter for dynamics generation of chemical concentrations

Chatani T., Shiraishi S., Miyazako H., Onoe H., Hori Y.

Royal Society Open Science （Royal Society Open Science）  10 （ 4 ）  2023年04月

　概要を見る

Cellular response to dynamic chemical stimulation encodes rich information about the underlying reaction pathways and their kinetics. Microfluidic chemical stimulators play a key role in generating dynamic concentration waveforms by mixing several aqueous solutions. In this article, we propose a multi-layer microfluidic chemical stimulator capable of modulating chemical concentrations by a simple binary logic based on the electronic-hydraulic analogy of electronic R-2R ladder circuits. The proposed device, which we call L-2L ladder digital-to-analogue converter (DAC), allows us to systematically modulate 2n levels of concentrations from single sources of solution and solvent by a single operation of 2n membrane valves, which contrasts with existing devices that require complex channel geometry with multiple input sources and valve operations. We fabricated the L-2L ladder DAC with n = 3 bit resolution and verified the concept by comparing the generated waveforms with computational simulations. The response time of the proposed DAC was within the order of seconds because of its simple operation logic of membrane valves. Furthermore, detailed analysis of the waveforms revealed that the transient concentration can be systematically predicted by a simple addition of the transient waveforms of 2n = 6 base patterns, enabling facile optimization of the channel geometry to fine-tune the output waveforms.

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Near-Infrared-Triggered On-Demand Controlled Release of Adeno-Associated Virus from Alginate Hydrogel Microbeads with Heat Transducer for Gene Therapy

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

Small （Small）  19 （ 7 ）  2023年02月

ISSN  16136810

　概要を見る

Gene therapy using adeno-associated virus (AAV) has potential as a radical treatment modality for genetic diseases such as sensorineural deafness. To establish clinical applications, it is necessary to avoid immune response to AAV by controlled release system of AAV. Here, a near-infrared (NIR)-triggered on-demand AAV release system using alginate hydrogel microbeads with a heat transducer is proposed. By using a centrifuge-based microdroplet shooting device, the microbeads encapsulating AAV with Fe3O4 microparticles (Fe3O4-MPs) as a heat transducer are fabricated. Fe3O4-MPs generated heat by NIR enhanced the diffusion speed of the AAV, resulting in the AAV being released from the microbeads. By irradiating the microbeads encapsulating fluorescent polystyrene nanoparticles (FP-NPs) (viral model) with NIR, the fluorescence intensity decreased only for FP-NPs with a diameter of 20 nm and not for 100 or 200 nm, confirming that this system can release virus with a diameter of several tens of nanometers. By irradiating NIR to the AAV-encapsulating microbeads with Fe3O4-MPs, the AAV is released on demand, and gene transfection to cells by AAV is confirmed without loss of viral activity. The NIR-triggered AAV release system proposed in this study increases the number of alternatives for the method of drug release in gene therapy.

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A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber

Komatsu T., Ohta H., Takakura N., Hata J., Kitagawa T., Kurashina Y., Onoe H., Okano H.J., Iguchi Y.

Translational Stroke Research （Translational Stroke Research）  2023年

ISSN  18684483

　概要を見る

The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n=14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3–8 min). Mean infarct volume was 388 mm3 (IQR, 354–420 mm3) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P = 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P < 0.001). We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of "pure" cell transplantation in treating stroke.

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Oil-Sealed Rgd-Modified Hydrogel Microwell Array with Size-Selective Permeation for Analysis on Exosomes from Single Cells

Yamagata C., Itai S., Kurashina Y., Asai M., Hoshino A., 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)）  2023-January   319 - 322 2023年

ISSN  10846999

　概要を見る

We propose an oil-sealed arginine-glycine-aspartate (RGD)-modified hydrogel microwell array for analyzing exosomes secreted from single cells. Our device realizes the collection of exosomes from single cells in parallel. The size-selective permeation of the RGD-modified alginate hydrogel allows both stable cell culturing of single or few cells in closed wells and the confinement of exosomes secreted in each space. The nutrients (< 20 nm) that are necessary for cell culture can pass through the hydrogel, while exosomes (30-150 nm) do not permeate the walls of microwells. The cell culture property and the permeability of our device were examined, showing the capability to collect exosomes from single cells. We believe that our device would contribute to understanding the mechanisms of various diseases.

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In-Ice Polymerization for Functional Hydrogel Microbead with Flash Freezing Centrifugal Microfluidic Device

Murayama T., Yoshida K., Kurashina Y., 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)）  2023-January   1084 - 1087 2023年

ISSN  10846999

　概要を見る

This paper describes a centrifuge-based fabrication method of microgel beads using flash freezing in liquid nitrogen and in-ice polymerization. Previously, materials for fabricating microgel beads with centrifugal microfluidic systems have been limited to only sodium alginate solution using rapid ionic cross-linking. By using our proposed method, the shape of beads can be defined by flash freezing of the ejected pre-gel microdroplets in liquid nitrogen and successive in-ice polymerization by UV irradiation. We succeeded in fabricating ethanol-responsive structural-color beads and confirmed their ethanol responsivity by exhibiting visible structural color change. Our fabrication method will expand the variety of materials for the centrifugal microfluidic microgel beads fabrication method and possible applications including biosensors and drug delivery systems.

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Controlling Firing Point of Microfiber-Shaped Hipsc-Derived Cardiac Tissue with Localized Electrical Stimulation Device

Masuda A., Itai S., Kurashina Y., Tohyama S., 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)）  2023-January   305 - 308 2023年

ISSN  10846999

　概要を見る

We propose a device to apply localized electrical stimulation to control cardiac conduction in in vitro cardiac tissue. Our system can initiate the generation of electrical impulses at any location by applying local electrical stimulation to the desired point of the microfiber-shaped cardiac tissue. Our system generated a strong and intense electric field between the electrodes in FEM analysis, indicating only the cardiac tissue between the electrodes was electrically stimulated. We could observe the cardiac conduction optically by visualizing the timing and location of impulses with calcium imaging at any location and time on the tissue. The system enables accurate analysis of cardiac potential and conduction velocity of the heart model, and could contribute to the elucidation of pathological dynamics such as arrhythmia, whose mechanism of occurrence still remains unknown.

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A Three-Dimensional Artificial Intestinal Tissue With A Crypt-Like Inner Surface

Tanaka S., Itai S., 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)）  2023-January   456 - 459 2023年

ISSN  10846999

　概要を見る

Disruption of the microbiome in humans caused several diseases. To infer causality, the intestinal models are essential, but the commonly used model has still room for improvements such as biomimicry, productivity, and ability to co-culture with bacteria. This paper describes the artificial intestinal tissue by culturing intestinal cells (Caco-2) in the collagen gel tube with crypt-like cavities created by electrolysis-triggered microbubbles. This tube device has high biomimicry and productivity and also consists of glass/silicone tubes connector at both ends, which allows for connecting external pumps easily and running two types of flows: the inside of the tube (internal flow) and permeation from the outside of the tube to the inside (external flow). In order to show this high extensibility, we demonstrated the co-culture of Caco-2 cells and bacteria (Bifidobacteria). We believe that our device will be a platform for investigating complex intestinal diseases due to its high biomimetic properties.

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Repeatable detection of Ag⁺ ions using a DNA aptamer-linked hydrogel biochemical sensor integrated with microfluidic heating system

Yoshida K., Hayashi T., Takinoue M., Onoe H.

Scientific Reports （Scientific Reports）  12 （ 1 ）  2022年12月

　概要を見る

This paper describes repeatable detection of Ag+ ions using a DNA aptamer-linked hydrogel biochemical sensor integrated with a microfluidic heating system. Biochemical sensors that respond to chemical compounds and produce detectable signals have a critical role in many aspects of modern society. In particular, the repeatable measurement of environmental information such as toxic substances including Ag+ ions could be expected to improve the environment. The DNA aptamer is an attractive candidate because of the stability and the selectivity of binding to chemicals. However, previous DNA aptamer biochemical sensors could not measure repeatedly because those sensors did not have initializing functions. To overcome this challenge, we proposed a DNA aptamer-linked hydrogel biochemical sensor integrated with the microfluidic heating system enabling repeatable detection of Ag+ ions. The binding Ag+ ions are dissociated by heating and flushing through the integrated microfluidic heating device. The DNA aptamer-linked hydrogel had the capability to detect a wide range of Ag+ ion concentrations (10−5–10 mM) including a toxic range for various aquatic organisms. Finally, we demonstrated the repeatable detection of the Ag+ ions. These results indicated that our proposed biochemical sensor is expected to use for long-term monitoring with high stability in ambient temperature and low power consumption.

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Light-driven flow control in the hydrogel microchannel by utilizing a metal microstructure fabricated by multiphoton photoreduction

Nagano Y., Onoe H., Terakawa M.

Optical Materials Express （Optical Materials Express）  12 （ 8 ） 3303 - 3312 2022年08月

　概要を見る

The light-stimulated control of flow velocity in the hydrogel microchannel was demonstrated by utilizing a metal microstructure fabricated by multiphoton photoreduction. The metal microstructure was fabricated adjacent to the microchannel in a poly-N- isopropylacrylamide (PNIPAm) hydrogel. Owing to the photothermal conversion at the metal microstructure, local deformation of the microchannel and change in flow velocity was induced as a result of the volume phase transition of the supporting hydrogel around the metal microstructure. Wavelength-selective change in the flow velocity was realized by utilizing dissimilar metal microstructures, that exhibit different optical resonances. The results indicate that multiphoton photoreduction is a promising method for fabricating novel hydrogel devices having flow-controllable switches by arranging light-absorbing structures with high spatial selectivity.

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Vascular embolization of radiopaque hydrogel microfiber using ultra-minimally invasive technique for stage-adjustable renal failure model

Takakura N., Ohta H., Komatsu T., Kurashina Y., Hiroka Y., Okano H.J., Onoe H.

Materials and Design （Materials and Design）  219 2022年07月

ISSN  02641275

　概要を見る

Animal pathology models play an important role in elucidating pathology, evaluating drug efficacy, and studying therapeutic. This paper presents the creation of rats’ renal failure model by embolizing the renal artery using radiopaque hydrogel microfibers. By using a dual coaxial laminar flow microfluidic device, barium alginate gel microfibers containing zirconia particles were fabricated. Since the zirconia particles are radiopaque, the microfiber can be delivered and embolized while confirming the position of the microfiber in real-time under X-ray imaging. The delivery of microfibers through a catheter into the renal artery of rats to create a renal failure model was tested. The radiopaque microfibers were visualized by X-ray imaging when delivered by a catheter. Furthermore, the microfibers remained stable for 2 weeks after delivery. In addition, by adjusting the number of microfibers, two different rat models with severe and mild renal failure conditions were created. The proposed delivery of radiopaque hydrogel microfibers to create an embolization model is expected to be an effective approach to control the degree of symptoms and elucidate the pathology.

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A novel fabrication process of up-scalable microfiber-shaped tendon-like tissue with high cell density for uniformed macroscale assembly

Fukada K., Tachibana K., Kurashina Y., Kaneko Y., Matsumoto T., Miyamoto T., Niki Y., Nakamura M., Onoe H.

Biotechnology and Bioengineering （Biotechnology and Bioengineering）  119 （ 5 ） 1327 - 1336 2022年05月

ISSN  00063592

　概要を見る

This paper describes up-scalable microfiber-shaped tissues for macroscale tendon tissue reconstruction in vitro. C3H10T1/2 cells were encapsulated in a calcium alginate hydrogel microfiber that was fabricated via a double coaxial microfluidic device. The C3H10T1/2 cells gradually merged to construct the microfiber-shaped tendon-like tissue. Our microfiber-shaped tendon-like tissues were alive and maintained their microfiber-shaped morphology over 600 days. Immunostaining and real-time quantitative polymerase chain reaction analyses showed that our fabricated microfiber-shaped tendon-like tissue properly expressed tenomodulin and the orientation of the filaments of actin, which are one of the characteristics of tendon tissue in vivo. Furthermore, a macroscale tendon tissue assembly with ∼1 cm in length and ∼200 µm in thickness was successfully constructed by bundling the microfiber-shaped tendon-like tissues together. This feature enabled us to fabricate a macroscale tendon tissue with uniform cell distribution. We believe that our fabricated microfiber-shaped tendon-like tissue would be a suitable strategy to reconstruct tendon tissue in vitro for the treatments of tendon-related injuries.

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Microfiber-Shaped Programmable Materials with Stimuli-Responsive Hydrogel

Takeuchi N., Nakajima S., Yoshida K., Kawano R., Hori Y., Onoe H.

Soft Robotics （Soft Robotics）  9 （ 1 ） 89 - 97 2022年02月

ISSN  21695172

　概要を見る

Programmable materials have artificially designed physical shapes responding to external stimuli, as well as high design capability and high flexibility. Here, we propose a microfiber-shaped programmable material with an axial pattern of stimuli-responsive (SR) and nonresponsive hydrogels. The SR pre-gel solution was mixed to sodium alginate pre-gel solution for instantaneous gelation with ionic crosslinking and solidified on a nonresponsive hydrogel microfiber with a valve-controlled microfluidic system. A design of microfiber-shaped programmable material (patterned position of SR regions) could be flexibly altered by changing a coded sequence program. We confirmed that the three-dimensional (3D) coil-like structures were self-folded at the patterned SR regions responding to the thermal stimulus and that the chirality of the self-folded 3D coil-like structures depends on the condition of the stimulus to the microfiber. Finally, interaction with objects using the programmable microfiber as a soft actuator was demonstrated. Our microfiber-shaped programmable materials expand possibilities of fiber-based materials in biomimetics and soft robotics fields.

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Microfluidic multicolor display by juxtapositional color mixing with a pattern of primary color pixels

Muramatsu J., Onoe H.

Journal of Micromechanics and Microengineering （Journal of Micromechanics and Microengineering）  32 （ 2 ）  2022年02月

ISSN  09601317

　概要を見る

This paper describes a microfluidic multicolor display utilizing juxtapositional color mixing of pixels. Our display has a 14 14 array of pixels (2.5 mm in pixel diameter, 8.46 ppi) on the display surface where multicolor is expressed by controlling the pattern of the four primary color inks (cyan (C), magenta (M), yellow (Y), and black (= key plate, K)) that fill the pixels. The microfluidic display has a three-layer structure composed of a top layer with pixels for displaying images, a middle layer that serves as a background screen, and a bottom layer with microchannels that connect the pixels. In order to express multicolor by combining CMYK primary colors, we optimized the concentration of the inks used as the primary colors. By designing patterns of pixels filled with CMYK ink, color gradations and multicolor images were displayed on our display. The proposed microfluidic display could be applied to eye-friendly and low-energy-consumption flexible display applications including multi-purpose sign boards used in outdoors, wearing objects, and exterior/interior of vehicles and architects.

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Flexibly Deformable Collagen Hydrogel Tube Reproducing Immunological Tissue Deformation of Blood Vessels as a Pharmacokinetic Testing Model

Itai S., Onoe H.

Advanced Healthcare Materials （Advanced Healthcare Materials）  11 （ 1 ）  2022年01月

ISSN  21922640

　概要を見る

Since the biochemical reaction of blood vessels plays an essential role in immune response or various diseases, in vitro vascular models have high demand from medical fields. However, vascular models often tend to be difficult to mimic the biomedical reaction faithfully because of the lack of implementation of the tissue deformation. Here, an inflammatory mediator-induced deformation reaction of a blood vessel on a flexibly deformable collagen hydrogel tube device is reproduced. A self-standing collagen tube enables the tissue to deform flexibly in biochemical reaction and achieves contraction both at tissue and cell level. The contraction of tissue relieves the stress between cells under reaction to maintain cellular junctions even tight junctions are broken. Also, the drug perfusion test with antihistamine chemical is easily performed due to the connector part and properly inhibits the inflammatory reaction. Moreover, the traction force on endothelial cells is analyzed as about 0.9 µN on two types of scaffolds with different stiffness. It is believed that the potential of the flexible tissue model to reproduce biochemical reactions can contribute to the fabrication of vascular tissue models mimicking in vivo in high similarity as a platform for biomedical researches and pharmacokinetic testing.

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Fixation-Free Evaluation of Cardiac Contractile Force by Human iPSC-Derived Cardiac Core-Shell Microfiber

Masuda A., Fukada K., Itai S., Kurashina Y., Akizuki S., Tohyama S., Fujita J., Onoe H.

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   172 - 175 2022年

ISSN  21601968

　概要を見る

We propose a core-shell microfiber-shaped cardiac tissue as a drug screening model with a fixation-free contractile force measurement system. The contractile force of the hiPSC-derived cardiac tissue can be calculated only with a motion analysis, thanks to a shell of hydrogel covering the cardiac tissue. Thus, the system can evaluate the behavior of the tissue in drug screenings without any specific equipment. We demonstrated drug screening tests with pharmaceuticals on our microfiber tissues, resulting in 102.7% increase of contractile force with isoproterenol and 56.3% decrease with propranolol. Our cardiac drug screening model can easily reproduce and evaluate cardiac disease models, and would contribute to the pathological research of unexplained cardiac diseases and pharmacokinetic testing.

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Tube-Shaped In-Vitro Intestinal Gut Model with 3D Isotropic Medium Supply for Bacterial Symbiosis

Kawahara M., Itai S., Onoe H.

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   321 - 324 2022年

ISSN  21601968

　概要を見る

This paper describes a tube-shaped in vitro intestinal gut model achieving both isotropic medium supply and stable co-culture with bacteria. Our tube-shaped device consists of a collagen/Matrigel tube as a scaffold for intestinal cells and glass/silicone tubes at both ends for perfusion. We confirmed intestinal cells (Caco-2) can be maintained in the luminal part with nutrient-free buffer flow mimicking bacterial suspensions and demonstrated the co-culture of Escherichia-coli (E. coli) in the Caco-2 cultured tube-shaped device. We believe this device provides ple but stable co-culture model with intestinal cells and bacteria and contributes to medical field research relating intestinal bacteria.

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Protein Expression Micro-Scale Mapping Analysis of Endothelial Tissue in in Vitro Branched Vascular Model under Mechanical Stimuli

Muramatsu J., Shimizu A., Hashimoto M., Miura S., Onoe H.

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   283 - 286 2022年

ISSN  21601968

　概要を見る

This paper describes a micro-scale mapping of protein expression on endothelial tissue in an extracellular matrix (ECM)-based branched microchannel under mechanical stimuli. Our system mimics the heterogeneity in the distribution of complex mechanical stimuli applied to tissues in vivo by applying mechanical stimuli to a branched vascular model. We confirmed the up-regulation of gene expression levels in vascular endothelial cells(ECs) by stretch stress. We cultured ECs under complex mechanical stimuli, and visualized the distribution of mechanotransducer protein expression in the branched vascular model. We believe that our system could open a new door for the analysis of local cellular responses to mechanical stimuli.

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Near Infrared-Triggered On-Demand Adeno-Associated Virus Release from Hydrogel Microbeads for Gene Therapy

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

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   388 - 391 2022年

ISSN  21601968

　概要を見る

This paper describes near infrared (NIR)-triggered on-demand adeno-associated virus (AAV) release from alginate hydrogel microbeads with heat transducer for gene therapy. As an AAV carrier, calcium alginate (Ca-Alg.) hydrogel microbeads were fabricated by injecting mixed pre-gel solution composed of sodium-alginate (Na-Alg.), AAV, and Fe3O4 particles (FPs: heat transducer) to CaCl2 solution to form ionically cross-linked instantly with a centrifuge-based microdroplet shooting device. The FPs generate heat due to localized surface plasmon resonance under NIR. By irradiating NIR to the microbeads, we confirmed the release of AAV and the gene transfection to HeLa cells. Our proposed NIR-triggered AAV release system would be an effective and safe controlled release system for gene therapy.

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Mechanically Magnified Sensitivity Enhancement with Micro-Step Substrate for Eye-Recognizable Structural-Color Hydrogel Biochemical Sensors

Yamawaki S., Onoe H.

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   739 - 742 2022年

ISSN  21601968

　概要を見る

We present a versatile device structure that can mechanically magnify the sensitivity of stimuli-responsive structural-color hydrogel biochemical sensors. In our system, the structural-color hydrogel part and the stimuli-response hydrogel part are separately arrayed on a substrate with micro-step structures, causing the height difference between the two hydrogel parts. This height difference magnifies the shrinkage ratio to be larger in the color part than in the stimulus-responsive part, achieving the x5 - x10 high sensitivity of the hydrogel-based biochemical sensor. We applied ethanol-responsive and temperature-responsive hydrogels to our proposed device and confirmed the magnification of the sensitivity compared to previous sensors. We believe that our sensor device will be an effective approach to providing sensing with practical sensitivity for medical and other applications.

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Ingestible Wireless Capsule Sensor Made from Edible Materials for Gut Bacteria Monitoring

Inami A., Kan T., Onoe H.

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   110 - 113 2022年

ISSN  21601968

　概要を見る

This report describes an ingestible capsule sensor that can wirelessly detect the activity of gut bacteria by irradiating microwaves from outside the body. The proposed sensor is composed of only edible materials: the critical sensing material is a dietary fiber, guar gum, that is decomposed by gut bacteria. We confirmed that the guar gum film can be decomposed by gut bacteria, bifidobacteria. For wireless communication, we fabricated an ingestible antenna made from rice paper and gold with a split-ring resonator (SRR), one of the elements of electromagnetic metamaterials. Our sensor fulfills swallowable size and wireless communication requirements for the first time and would be a safety sensor for gastrointestinal (GI) tract monitoring. We believe that our ingestible sensor could be an effective tool for non-invasive biological substances monitoring without retention risk.

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In Vitro Artery Model with Circumferentially Aligned &amp; Contractible Smooth Muscle by Unfixed Molding &amp; Screwing Fabrication

Itai S., Onoe H.

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   275 - 278 2022年

ISSN  21601968

　概要を見る

This paper describes a fabrication method of an artery model with circumferentially aligned and contractible smooth muscle cells (SMCs) by unfixed molding and screwing processes. The fabricated aligned smooth muscle is well-deformable, enabling the flexible contraction in biological reaction. The axially aligned fiber-shaped smooth muscle tissue was formed by unfixed molding and screwed up to be aligned circumferentially. Also, the SMC layer was covered with a collagen layer with connectors to enable co-culture with endothelial cells (ECs) and perfusion culture. The alignment of SMCs was visibly confirmed, and the ability to reproduce the biochemical contraction was proved by an inflammatory reaction. We believe that our novel fabrication method would contribute to the development of functional smooth muscle models for biomedical researches.

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Glass-Capillary-Embedded 3D Coaxial Microfluidic Device with Pneumatic Microvalve Control for Producing Patterned Functional Materials

Takakura N., Kurashina Y., Onoe H.

IEEE Symposium on Mass Storage Systems and Technologies （IEEE Symposium on Mass Storage Systems and Technologies）  2022-January   267 - 270 2022年

ISSN  21601968

　概要を見る

This paper describes a glass-embedded poly-dimethyl-siloxane microfluidic device with integrated microvalves to create a patterned 3D coaxial flow for producing functional composite materials. The microfluidic device was fabricated by transferring two layers of PDMS onto acrylic molds and bonding them across a glass capillary. We confirmed that the microfluidic device could flow coaxial flow and switch the solution. We demonstrated that core-shell microfibers with shells patterned in two different directions by flowing three different sodium alginate solutions into the microfluidic device. Our proposed microfluidic device would be used to fabricate multifunctional hydrogel microfibers made of multiple materials, which can be applied to bio-fabrication and soft-actuator.

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WIRELESS SOIL PH SENSING IN OUTDOOR ENVIRONMENT WITH PH-SELECTIVE FULLY-DEGRADABLE METAMATERIAL ANTENNA

Sakabe K., Kan T., 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）     217 - 218 2022年

　概要を見る

We propose a wireless and battery-free soil pH sensor made entirely of degradable materials for soil pH monitoring in outdoor environments. The sensor consists of magnesium (Mg) electric antenna based on inductor-capacitor circuit resonance with hydroxyapatite (Ca10(PO4)6(OH)2, HA) coating, enabling degradation of the sensor in acid soil conditions. In this report, we succeeded in measuring the changes over time of different electromagnetic responses in soils with different soil pH. Furthermore, the electromagnetic response of the sensor was also demonstrated in the outdoor field experiment. We believe that our biodegradable soil pH sensor could apply to low-cost, in situ, and environmentally friendly monitoring of soil pH.

A THREE-DIMENSIONAL ARTIFICIAL INTESTINAL TUBE WITH A CRYPT-LIKE INNER SURFACE FORMED BY ELECTROLYTIC MICROBUBBLES

Tanaka S., Itai 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）     13 - 14 2022年

　概要を見る

Crypts-like structures are indispensable to fabricating an artificial intestinal tissue reproducing the arrangement of cell types in vivo. This paper presents fabrication of an artificial intestinal tube with an uneven inner wall created by electrolysis-triggered microbubbles. During the fabrication process of a scaffold, microbubbles were generated on a tungsten electrode to form cavities on the inner surface of the collagen hydrogel tube. The method can fabricate numerous crypt-like structures in the order of a hundred micro-meter quickly. We believe that our device will be a platform for investigating complex intestinal diseases due to its high biomimetic properties.

L-2L LADDER MICROFLUIDICS FOR DYNAMIC GENERATION OF CHEMICAL CONCENTRATIONS

Shiraishi S., Chatani T., Miyazako H., Onoe H., Hori Y.

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）     897 - 898 2022年

　概要を見る

System-level understanding of dynamic biological process requires the measurement of the dynamic response of cells to chemical stimulations with various waveforms. Here, we develop a simple and scalable microfluidic chemical stimulator capable of modulating the concentration waveforms. The proposed device is based on the analogy of an electronic digital-analog converter (DAC), and thereby, the waveforms can be controlled by an intuitive binary logic. We demonstrate dynamic modulation of solution concentrations and perform systematic characterization of the waveforms to enable facile tuning and scale-up of the device.

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

　概要を見る

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.

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）     528 - 529 2022年

　概要を見る

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

　概要を見る

Light-driven control of the flow velocity inside a hydrogel microchannel is demonstrated by fabricating metal microstructures by multiphoton photoreduction. A technique to evaluate the local strain and compression of the hydrogel will also be described.

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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

　概要を見る

Light-driven control of the flow velocity inside a hydrogel microchannel is demonstrated by fabricating metal microstructures by multiphoton photoreduction. A technique to evaluate the local strain and compression of the hydrogel will also be described.

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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.

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）     466 - 467 2022年

　概要を見る

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.

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）     532 - 533 2022年

　概要を見る

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.

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）     362 - 363 2022年

　概要を見る

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

　概要を見る

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

　概要を見る

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

　概要を見る

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.

21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021 （21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021）     835 - 838 2021年06月

　概要を見る

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.

21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021 （21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021）     863 - 866 2021年06月

　概要を見る

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.

21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021 （21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021）     1000 - 1003 2021年06月

　概要を見る

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.

21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021 （21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021）     283 - 286 2021年06月

　概要を見る

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

　概要を見る

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

　概要を見る

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

　概要を見る

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

　概要を見る

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.

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   26 - 29 2021年01月

ISSN  9781665419123

　概要を見る

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.

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   775 - 778 2021年01月

ISSN  9781665419123

　概要を見る

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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Shape Retaining and Sacrificial Molding Fabrication Method for ECM-Based in vitro Vascular Model

Muramatsu J., Goh W.H., Shimizu A., Hashimoto K., Hashimoto M., Miura S., 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   230 - 233 2021年01月

ISSN  9781665419123

　概要を見る

This paper describes a new fabrication method for the extracellular matrix (ECM)-based in vitro vascular model. The vascular model was fabricated with shape retaining mold and sacrificial mold (shape retaining and sacrificial molding, SRS-molding). We compared SRS-molding and sacrificial molding. In addition, complex mechanical stimuli such as stretching and flowing in the branches of the vascular model were analyzed by simulation software. Finally, we performed the perfusion culturing with our vascular model and stretching them. Our vascular model and mechanical stimuli analysis would elevate the vascular culturing to the next step.

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Real-Time Three-Dimensional Single-Cell-Resolution Monitoring System for Observation of Dynamic Cell Behavior under Mechanical Stimuli

Kasahara K., Kurashina Y., Miura S., Miyata S., 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   454 - 457 2021年01月

ISSN  9781665419123

　概要を見る

We present an experimental system for real-time monitoring of 3D constructed tissues at single-cell resolution to further understand cellular response against mechanical stimuli. The system enables us to continuously monitor the same cells in a 3D tissue at a subcellular level under uniaxial cyclic stretch. We confirmed our system's effectiveness by observing that 3D tissues cultured under cyclic stretch were oriented to the direction of stretch. Moreover, cells in a 3D tissue were successfully observed continuously at single-cell resolution even under cyclic stretch. We believe that the real-time observation of cellular response against mechanical stimuli with our demonstrated system could be an effective method for investigating the relationship between cellular response and mechanical stimuli in detail.

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On-The-Fly Rapid-Cooling Gelation of Microgel Beads in Centrifugal Microfluidic Device with Liquid Nitrogen

Murayama T., Tsuchiya M., Yoshida K., Kurashina Y., 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   1027 - 1030 2021年01月

ISSN  9781665419123

　概要を見る

This paper describes a new fabrication method of microgel beads crosslinked by rapid temperature change using a centrifugal microfluidic device with a heating system and liquid nitrogen. Previously, materials for fabricating microgel beads with centrifugal microfluidic systems is limited to only sodium alginate solution. By using our proposed method, microgel beads could be fabricated by rapidly cooling pre-gel droplet ejected by centrifugal force. We succeeded in fabricating agarose microgel beads by rapid gelation in the liquid nitrogen. Our fabrication method will expand the variety of materials for the centrifugal microfluidic microgel beads fabrication method and possible applications including biosensors, tissue engineering and drug delivery systems.

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Ethanol Driven Micro-Robots with Photonic Colloidal Crystal Hydrogel for Exploring and Sensing Stimuli

Yoshida K., Yamawaki S., 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   47 - 50 2021年01月

ISSN  9781665419123

　概要を見る

Photonic colloidal crystal hydrogels are expected to be a powerful tool for environmental monitoring and healthcare. The photonic colloidal crystal hydrogel reflects visible-light, so the intensity of the stimulus can be converted to visible color. However, these sensors required taking a measured sample from the target environment. To detect a specific substance in a vast environment, exploring and detecting systems are required. Therefore, we proposed ethanol driven micro-robots with photonic colloidal crystal hydrogel. We achieved the color changes of micro-robots response to the external stimuli. Proposed micro-robots propelled over 600 s by the Marangoni effect caused by ethanol diffusion.

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Electrical Field Chamber with Dinamically Adaptable Stimuli for Myocyte Orientation during Cultivation

Ramirez S.R.M., Yamada T., Funahashi A., 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   498 - 501 2021年01月

ISSN  9781665419123

　概要を見る

Tissue engineering is a promising technology for both its possible applications in the fields of regenerative medicine and medical research. One of its challenges is to create an environment which allows the cell cultures to develop correctly. This environment is far from static and normally is modified by the cells themselves. To this end, adaptable systems have to be developed to ensure a successful development of the in-vitro tissue. This research focuses on a system which is able to modify an external electrical stimulus on a culture chamber, during its cultivation. This system, through a variation of the stimulus direction, successfully improved the orientation of the developing myocytes.

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Anionic fluorophore-assisted fabrication of gold microstructures inside a hydrogel by multi-photon photoreduction

MACHIDA M., SHEN W., ONOE H., HIRUTA Y.U.K.I., HEISTERKAMP A., MAZUR E.R.I.C., TERAKAWA M.

Optical Materials Express （Optical Materials Express）  11 （ 1 ） 48 - 58 2021年01月

　概要を見る

The fabrication of accentuated gold microstructures is demonstrated by multi-photon photoreduction inside an anionic fluorophore-containing hydrogel. We attempted to facilitate gold-ion photoreduction near the focal point of laser pulses, expecting the donation of electrons by the oxidation of fluorophores in the vicinity of gold ions. The presence of anionic FITCdextran also inhibited the spontaneous reduction in untargeted zones, which is attributed to the coordination of gold ions and the anionic FITC-dextran. Simultaneous facilitation and inhibition are promising for the fabrication of dense metal microstructures in the targeted zone while maintaining the hydrogel's light permeability.

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Charged fluorophores-assisted fabrication of metallic structures inside hydrogel by multi-photon photoreduction

MacHida M., Shen W., Onoe H., Heisterkamp A., Mazur E., Terakawa M.

Proceedings of SPIE - The International Society for Optical Engineering （Proceedings of SPIE - The International Society for Optical Engineering）  11676 2021年

ISSN  9781510641877

　概要を見る

We demonstrated the fabrication of gold microstructures inside a PEG-based hydrogel with different charged fluorophores by multi-photon photoreduction. By adding an anionic charged FITC-dextran or a cationic charged Rhodamine110 to the metal ion solution, line width of the fabricated gold microstructures increased compared to that of the structures fabricated in fluorophore-free hydrogel. The photobleaching could enhanced the reduction of gold ions accompanying the oxidation of the fluorophores. Notably, the inhibition of reduction of gold ions at a site other than the focal point was observed with FITC-dextran, which may be attributable to the coordination of gold ions to FITC-dextran.

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Travelling ultrasound promotes vasculogenesis of three-dimensional-monocultured human umbilical vein endothelial cells

Imashiro C., Azuma T., Itai S., Kuribara T., Totani K., Onoe H., Takemura K.

Biotechnology and Bioengineering （Biotechnology and Bioengineering）  118 （ 10 ） 3760 - 3769 2021年

ISSN  00063592

　概要を見る

To generate three-dimensional tissue in vitro, promoting vasculogenesis in cell aggregates is an important factor. Here, we found that ultrasound promoted vasculogenesis of human umbilical vein endothelial cells (HUVECs). Promotion of HUVEC network formation and lumen formation were observed using our method. In addition to morphological evaluations, protein expression was quantified by western blot assays. As a result, expression of proteins related to vasculogenesis and the response to mechanical stress on cells was enhanced by exposure to ultrasound. Although several previous studies have shown that ultrasound may promote vasculogenesis, the effect of ultrasound was unclear because of unregulated ultrasound, the complex culture environment, or two-dimensional-cultured HUVECs that cannot form a lumen structure. In this study, regulated ultrasound was propagated on three-dimensional-monocultured HUVECs, which clarified the effect of ultrasound on vasculogenesis. We believe this finding may be an innovation in the tissue engineering field.

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ATP-DRIVEN MUSCLE INTEGRATED MICROROBOT ACTUATED BY TRACTION OF ACTOMYOSIN-COLLAGEN HIBRID HYDROGEL

Kohno K., Hiratsuka Y., Onoe H.

MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     619 - 620 2021年

　概要を見る

We propose an elastomeric microrobot actuated by ATP-driven biological traction of actomyosin. Our robot is composed of a PDMS thin film part as a body and an actomyosin-embedded collagen hydrogel part as a linear motor. The actomyosin drives the hydrogel linear motor by the hydrolysis of ATP. This actomyosin linear motor could repeatably contract by adding ATP and stretching similar to the driving mechanism of our body. By combining the linear motor part and PDMS actuator part, we succeeded in driving the whole device by the traction force of actomyosin. The traction force generated by the linear motor was estimated from the deformation of the PDMS body. We believe that our device would be a new approach to apply biological motor for micro actuators.

ULTRASOUND-TRIGGERED ON-DEMAND ADENO-ASSOCIATED-VIRUS RELEASE FROM HYDROGEL MICROBEADS FOR GENE THERAPY

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

MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     655 - 656 2021年

　概要を見る

This paper reports ultrasound-triggered adeno-associated-virus (AAV) release from alginate hydrogel microbeads loaded into a gelatin hydrogel carrier to promote the transfection of cells. As a AAV carrier, caldium alginate hydrogel microbeads were centrifugally fabricated by ejecting a mixed pre-gel solution composed of sodium alginate, AAV and tungsten particles to CaCl2 solution to form ionically cross-linked instantly. For fixing of the beads, the microbeads were loaded into gelatin hydrogel carriers. The tungsten particles having high acoustic impedance enable the beads to have high sensitivity to ultrasound for improvement of the transfection. Our proposed ultrasound-triggered AAV releasing system would be an effective controlled release system for gene therapy.

PULSATILE FLOW ANALYSIS AT BRANCHED POINT IN ECM-BASED ENDOTHELIAL VASCULAR MODEL UNDER MECHANICAL STRETCH

Muramatsu J., Hashimoto M., Miura S., Onoe H.

MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     305 - 306 2021年

　概要を見る

This paper describes a stretchable extracellular matrix (ECM)-based in vitro endothelial vascular model with branched channels that can reproduce mechanically driven pulsatile flow. We imaged and analyzed the pulsatile flow at the branched points that are unique structures of blood vessels. The analysis revealed characteristic flow streams to the cultured endothelial cells near the branched points. We believe that our system would reveal the complex mechanical cellular response in blood vessels and enable the construction of mature in vitro vascular tissues.

GLUCOSE-MONITORING JANUS HYDROGEL MICROBEADS WITH COMPENSATION FUNCIONS FOR SURROUNDING PH ENVIRONMENT

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

MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     1129 - 1130 2021年

　概要を見る

This paper presents Janus microbeads for continuous fluorescent glucose monitoring with pH calibration. By using an UV- assisted centrifugal microfluidic device, the Janus hydrogel microbeads that consist of glucose sensor and pH sensor are easily fabricated. The microbead can calibrate the pH values of its surroundings and enables accurate measurements of glucose among various pH conditions. As a proof of concept, an accurate measurement of glucose concentration in the body-fluid-like solution using fluorescent intensities from glucose and pH sensor in microbeads was demonstrated. We believe that our fluorescent microbeads, with pH-calibration capacity, could be applied to fully implantable sensors for continuous glucose monitoring for diabetics.

CATHETER DELIVERY OF RADIOPAQUE CELL-ENCAPSULATED HYDROGEL MICROFIBERS FOR CELL THERAPY

Takakura N., Ohta H., Komatsu T., Kurashina Y., Okano H.J., Onoe H.

MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     109 - 110 2021年

　概要を見る

This paper proposes a cell-encapsulated core-shell radiopaque hydrogel microfiber for in vivo cell therapy. The microfiber is composed of barium alginate gel containing zirconia particles in the shell and collagen gel encapsulating mesenchymal stem cells in the core. We confirmed that the cells in the fiber secrete paracrine factors to the outside of the fiber. Moreover, we demonstrated the improvement of the renal function of the rats by delivering the fiber into renal arteries. We believe that our fiber would treat incurable diseases including tissue degeneration.

Cell-encapsulated chitosan-collagen hydrogel hybrid nerve guidance conduit for peripheral nerve regeneration

Itai S., Suzuki K., Kurashina Y., Kimura H., Amemiya T., Sato K., Nakamura M., Onoe H.

Biomedical Microdevices （Biomedical Microdevices）  22 （ 4 ）  2020年12月

ISSN  13872176

　概要を見る

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Nerve guidance conduits (NGCs) composed of biocompatible polymers have been attracting attention as an alternative for autograft surgery in peripheral nerve regeneration. However, the nerve tissues repaired by NGCs often tend to be inadequate and lead to functional failure because of the lack of cellular supports. This paper presents a chitosan-collagen hydrogel conduit containing cells to induce peripheral nerve regeneration with cellular support. The conduit composed of two coaxial hydrogel layers of chitosan and collagen is simply made by molding and mechanical anchoring attachment with holes made on the hydrogel tube. A chitosan layer strengthens the conduit mechanically, and a collagen layer provides a scaffold for cells supporting the axonal extension. The conduits of different diameters (outer diameter approximately 2–4 mm) are fabricated. The conduit is bioabsorbable with lysozyme, and biocompatible even under bio absorption. In the neuron culture demonstration, the conduit containing Schwann cells induced the extension of the axon of neurons directed to the conduit. Our easily fabricated conduit could help the high-quality regeneration of peripheral nerves and contribute to the nerve repair surgery.

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Multiphoton photoreduction for dual-wavelength-light-driven shrinkage and actuation in hydrogel

Mizuguchi K., Nagano Y., Nishiyama H., Onoe H., Terakawa M.

Optical Materials Express （Optical Materials Express）  10 （ 8 ） 1931 - 1940 2020年08月

　概要を見る

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. The dual-wavelength-driven shrinkage of metal microstructures and hydrogel actuation are demonstrated by the fabrication of multi-metal microstructures in hydrogels by multiphoton photoreduction. Silver and gold microstructures were fabricated in a poly-Nisopropylacrylamide (PNIPAm) hydrogel. Because of the different optical resonances of the metals, wavelength-dependent shrinkage of metal microstructures was demonstrated concurrently with the volume change of the supporting hydrogel by light stimulation. Furthermore, the direction of actuation of the hydrogel was controlled by switching the wavelength of light stimulation. The results indicate the potential of multiphoton photoreduction for applications in light-driven optical components and micro-robots fabricated with soft materials.

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ECM-based microfluidic gradient generator for tunable surface environment by interstitial flow

Shimizu A., Goh W.H., Itai S., Karyappa R., Hashimoto M., Onoe H.

Biomicrofluidics （Biomicrofluidics）  14 （ 4 ）  2020年07月

ISSN  19321058

　概要を見る

© 2020 Author(s). We present an extracellular matrix (ECM)-based gradient generator that provides a culture surface with continuous chemical concentration gradients created by interstitial flow. The gelatin-based microchannels harboring gradient generators and in-channel micromixers were rapidly fabricated by sacrificial molding of a 3D-printed water-soluble sacrificial mold. When fluorescent dye solutions were introduced into the channel, the micromixers enhanced mixing of two solutions joined at the junction. Moreover, the concentration gradients generated in the channel diffused to the culture surface of the device through the interstitial space facilitated by the porous nature of the ECM. To check the functionality of the gradient generator for investigating cellular responses to chemical factors, we demonstrated that human umbilical vein endothelial cells cultured on the surface shrunk in response to the concentration gradient of histamine generated by interstitial flow from the microchannel. We believe that our device could be useful for the basic biological study of the cellular response to chemical stimuli and for the in vitro platform in drug testing.

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ECM-based microchannel for culturingin vitrovascular tissues with simultaneous perfusion and stretch

Shimizu A., Goh W.H., Itai S., Hashimoto M., Miura S., Onoe H.

Lab on a Chip （Lab on a Chip）  20 （ 11 ） 1917 - 1927 2020年06月

ISSN  14730197

　概要を見る

© The Royal Society of Chemistry 2020. We present an extracellular matrix (ECM)-based stretchable microfluidic system for culturingin vitrothree-dimensional (3D) vascular tissues, which mimicsin vivoblood vessels. Human umbilical vein endothelial cells (HUVECs) can be cultured under perfusion and stretch simultaneously with real-time imaging by our proposed system. Our ECM (transglutaminase (TG) cross-linked gelatin)-based microchannel was fabricated by dissolving water-soluble sacrificial polyvinyl alcohol (PVA) molds printed with a 3D printer. Flows in the microchannel were analyzed under perfusion and stretch. We demonstrated simultaneous perfusion and stretch of TG gelatin-based microchannels culturing HUVECs. We suggest that our TG gelatin-based stretchable microfluidic system proves to be a useful tool for understanding the mechanisms of vascular tissue formation and mechanotransduction.

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ECM-Based Gradient Generator for Tunable Surface Environment by Interstitial Flow

Shimizu A., Goh W.H., Karyappa R.B., Hashiomoto M., 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)）  2020-January   122 - 124 2020年01月

ISSN  9781728135809

　概要を見る

© 2020 IEEE. We present an extracellular matrix(ECM)-based microfluidic device that creates a spatial chemical gradient by interstitial flow. Cells located on surfaces of ECM, such as vascular and skin tissues, are influenced by external factors, including interstitial flows, but few methods have been available to recapitulate such conditions. To address this gap, we developed a microfluidic device that can expose cells cultured on the surface of ECM to a continuous concentration gradient created by the interstitial flow. With a 3D printed water-soluble sacrificial mold, we readily fabricated ECM-based microfluidic devices embedding micromixers and a gradient generator. ECM mimicked the permeability of in vivo environments. Our device will serve as a platform to study cellular phenomena occurring on the surface of ECM, such as vascularization and migration of cancer cells.

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Self-Folding Acute-Angle Origami Driven by Surface Bending Force

Uchida T., Yasuga H., Tachi T., Iwase E., 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)）  2020-January   992 - 993 2020年01月

ISSN  9781728135809

　概要を見る

© 2020 IEEE. This study describes a self-folding origami technique that enables acute angle folding by surface bending force for the first time. We patterned plus-shaped '+' carbon black patterns on a shrinking sheet and achieved self-folding of the 2D sheet quite sharply (more than 160°) trigger with infrared (IR) light irradiation. We investigated the folding angle of our sheet with '+' pattern comparing to the sheet with slit pattern on a crease, and confirmed that our sheet could be folded at larger folding angle than the sheet with slit pattern. Next, we examined the folding angle of the sheet that had '+' pattern with different width and found that the folding angle increased when the surface bending force increased. Finally, we demonstrated this '+' pattern to fabricate 3D word objects 'MEMS'. Our surface bending approach to Origami folding could open a new avenue to widen the variety and controllability of self-folding objects.

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PNIPAM/SWCNT-Based Hydrogel Micro-Gripper Driven by Infrared Light for Intravascular Surgery

Kuroda T., 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)）  2020-January   540 - 541 2020年01月

ISSN  9781728135809

　概要を見る

© 2020 IEEE. This paper describes an infrared (IR) light-responsive hydrogel micro-gripper for intravascular surgery. The hydrogel micro-gripper was fabricated by two-step photolithography that can design the motion of gripper. The gripping motion was controlled by IR exposure that was efficiently and selectively absorbed by the single walled carbon nanotubes (SWCNT) to generate heat. We confirmed the gripping speed in micro-scale gripper (width: sim 200 mumathrm{m}) was faster than that of the large scale (width: ∼2 mm). We demonstrated the hydrogel micro-gripper firmly gripped and kept holding a 200-mumathrm{m}-diameter bead with the chamber being shaken. We believe that our hydrogel micro-gripper can be applied for medical applications such as low-invasive medical practices because it could grip cells or foreign objects by being exposed to IR light irradiated from outside of the body.

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One-Step Fabrication of Multi-Functional Core-Shell Janus Microparticles for Theranostics Application

Tsuchiya M., Kurashina Y., Heo Y.J., 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)）  2020-January   32 - 35 2020年01月

ISSN  9781728135809

　概要を見る

© 2020 IEEE. We present a one-step method to fabricate microparticles to detect substances and release drugs in our bodies. Our microparticles have two compartments and an outer shell. The two compartments (Janus cores) enable the encapsulation of different materials separately for diagnosis and therapy while the outer shell reduces the adhesion and protects the encapsulated materials. These multi-functional core-shell Janus microparticles are fabricated by simply ejecting pre-gel solutions into a calcium chloride solution under centrifugal gravity application and UV irradiation. Moreover, we implanted these microparticles in biological tissue and demonstrated the transdermal sensing and drug model release. We believe that our fabrication method and particle design could be an effective approach for multi-functional smart theranostic medicine.

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Microfluidic Reflective Display with Primary Color Sub-Pixels

Muramatsu J., 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)）  2020-January   1161 - 1162 2020年01月

ISSN  9781728135809

　概要を見る

© 2020 IEEE. This paper describes a multi-color microfluidic reflective display with sub-pixels. Our display is composed of four independent three-dimensional (3D) PDMS microchannels where CMYK (Cyan, Magenta, Yellow, Key plate) ink droplets are spatially positioned as CMYK sub-pixels. By combining CMYK sub-pixel colors, our device displays multiple colors on a single pixel. We evaluated the optical characteristics of each CMYK sub-pixels and confirmed that multi-colors can be displayed by adjusting the combination of sub-pixel colors. We believe that our display could be applied to next-generation wearable displays and sign boards as a low-energy consumption, flexible and full-color reflective display.

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Locally Bendable Stimuli-Responsive Hydrogel Actuator with Axially Patterned Functional Materials

Takeuchi N., Nakajima S., Kawano R., Hori Y., 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)）  2020-January   243 - 244 2020年01月

ISSN  9781728135809

　概要を見る

© 2020 IEEE. This paper describes a locally bendable stimuli-responsive hydrogel actuator with axially patterned functional materials fabricated by a valve-controlled microfluidic device. By application of an external stimuli to the complete actuator, it can be locally bended owing to the axial pattern of the responsive and non-responsive material. These materials are axially patterned on a microfiber through the Y-shaped channel coupled with the open/close motion of the valves in the microfluidic device. The microfluidic device can regulate the on/off of the flow by thin membrane pneumatic valves controlled by a computer. The patterning frequency of the two materials in the microfiber could be adjusted by modifying the switching intervals of the solutions. Also, we successfully demonstrated the curvature-change through heating and cooling. We believe that this locally bendable stimuli-responsive hydrogel could contribute to microfiber-shaped soft actuators, biomedical sensors, and self-assembly of complex 3D microstructures.

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Microfluidic-based multicolor reflective display using water/air microdroplet trains

Kobayashi K., Onoe H.

21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017 （21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017）     744 - 745 2020年

ISSN  9780692941836

　概要を見る

© 17CBMS-0001. This paper describes a microfluidic-based multicolor reflective display using dyed water droplets as pixel elements. Our display was composed of a PDMS sheet with a connected pixel-patterned microchannel. Several types of water droplets and air gaps were sequentially introduced in the microchannel by sucking with a syringe pump to display . We evaluated the stability of minimum continuous number of water and air dots to display images correctly. We demonstrated displaying three colored dot-matrix reflective images. We believe that our display could be applicable to energy-less and color-changeable displays for future advertising signage or accessories including bags, shoes, or cloths.

Graphene-based inline pressure sensor integrated with elastic microfluidic tube

Inoue N., Onoe H.

21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017 （21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017）     609 - 610 2020年

ISSN  9780692941836

　概要を見る

© 17CBMS-0001. This paper describes a poly-dimethylsiloxane (PDMS) microfluidic tube integrated with graphene sheets for an inline flow pressure sensor. The PDMS tube was fabricated by molding and a graphene sheet was transferred on the surface of the PDMS tube. Pressure caused by fluid flow inside the tube was monitored by changes in the electric resistance of the transferred graphene. Our pressure sensor could be suitable for precise pressure measurement of small amount of fluid in microfluidic systems including organ-on-a-chip devices.

Double-layer collagen microtube for perfusable heterogeneous culture

Itai S., Onoe H.

21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017 （21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017）     1137 - 1138 2020年

ISSN  9780692941836

　概要を見る

© 17CBMS-0001. We present a double-layer collagen microtube device for in vitro perfusable multilayered 3D cell culture. Thicknesses of the collagen layers in the microtube can flexibly designed, and heterogeneous types of cells can be co-cultured in each collagen layer or surfaces. Moreover, while our collagen tube is directly attached to silicone tubes, the collagen microtube can be easily connected to an external pump system for perfusion culture. We believe that our device could help easy fabrication of various tissue models mimicking in vivo, especially blood vessel models or vascularized skin models, and contribute to the development of pharmacokinetic testing platforms and regenerative medicine.

Actomyosin-collagen hybrid soft actuator

Kohno K., Kwara S., Hiratsuka Y., Onoe H.

MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     997 - 998 2020年

ISSN  9781733419017

　概要を見る

Soft actuators mimicking biological muscles have been built by polymerizing actin and myosin in vitro to construct actomyosin, however, the mechanical strength of the actomyosin was generally not sufficient for practical uses as an actuator. In this study, we proposed an actomyosin-collagen hybrid actuator with high mechanical strength and formability by reconstructing actomyosin biomolecular linear motors inside collagen gel matrix. This actuator can be contracted by adding ATP and returned to its original length by applying an external tensile force, resulting that the actuator could be driven multiple times. This actuator could be expected as an actuator for environment-friendly micro-robots and wearable medical devices.

Wireless and battery-free digestible sensor for intestinal bacteria monitoring

Inami A., Iyama E., Itai S., Onoe H.

MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     575 - 576 2020年

ISSN  9781733419017

　概要を見る

We propose a wireless and battery-free digestible sensor for the detection of intestinal bacteria. This device has a dissolvable Mg planer coil that is covered with a coating layer composed of dietary fiber. This dietary fiber layer is selectively degraded by intestinal bacteria, resulting in the dissolution of the Mg coil that can be wirelessly monitored without any internal batteries. In this report, in vitro wireless detection on the degradation of our device was demonstrated as a proof-of-concept experiment. We believe that this device could be a new non-toxic easy-monitoring device for detecting biological substances without heavy burden to human.

Stimuli-responsive hydrogels embedding mechanichal metamaterials for high sensitive biochemical sensors

Yamawaki S., Tsuchiya M., Onoe H.

MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     593 - 594 2020年

ISSN  9781733419017

　概要を見る

This paper describes a novel approach to magnify the shrink/swell degree of stimuli-responsive hydrogels with micro-scale mechanical metamaterials. The mechanical matematerial fabricated by two-photon stereolithography can be embedded in a structural-color stimuli-responsive hydrogels to amplify the sensitivity (the change in structural color) (Figure 1). To prove this concept, we here constructed micro-scale mesh-like structures with negative poisson ratio. By responding to an applied displacement of 'z = 50 μm, this structure expanded to 'x = 90 μm, showing its displacement amplification. The fabricated structures embedded in poly-N-isopropylacrylamide (PNIPAM) hydrogel showed that the shrinkage of the PNIPAM hydrogel successfully drive the embedded mechanical-metamaterial structures. We believe that this system would be an effective approach to increase the sensitivity of the structural color gel sensors for practical applications.

Radiopaque hydrogel microfiber for arterial embolization

Takakura N., Ohta H., Komatsu T., Kurashina Y., Okano H.J., Onoe H.

MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     320 - 321 2020年

ISSN  9781733419017

　概要を見る

This paper proposes a radiopaque hydrogel microfiber for arterial embolization. The microfiber is made of barium alginate hydrogel containing zirconia (Radiopaque), and fabricated in a dual coaxial laminar flow microfluidic device. We confirmed that X-ray imaging was possible by encapsulating zirconia particles in hydrogel microfibers. Moreover the microfiber was successfully delivered into the target arteries of rats using a catheter to block blood flow for a long time. We believe that this microfiber would enable arterial embolization of cancerous tissues in various organs.

Quantitative design strategy of the resolution and screen area of microfluidic reflective display with sub-pixels

Muramatsu J., Onoe H.

MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences （MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences）     310 - 311 2020年

ISSN  9781733419017

　概要を見る

This paper discusses the design of the multi-color microfluidic display with sub-pixels. Our display has four primary color sub-pixels in the single pixel, and displays various colors by controlling the ON/OFF of sub-pixels. To show clear images, small sub-pixels and large screen are required, but the driving pressure of the fluid limits the design. Then, we calculated the driving pressure, and led the quantitative design strategy. Finally, we confirmed the smoother color mixing by high resolution and large screen display.

DNA Aptamer-Linked Structural-Color Hydrogel for Repeatable Biochemical Sensing

Hayashi T., Takinoue M., Onoe H.

2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII （2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII）     582 - 585 2019年06月

ISSN  9781728120072

　概要を見る

© 2019 IEEE. This paper describes a DNA aptamer-linked structural-color hydrogel sensor that can quantitatively and repeatably detect biochemical substances through visual information without any specific equipment. The initial color of structural-color hydrogel could be adjusted by controlling the concentration of the colloidal silica particle. We co-polymerized a DNA aptamer that specifically binds to silver ions into acrylamide hydrogel and evaluated its quantitative shrinking response to silver acetate solution. In addition, we succeeded in initializing our DNA aptamer hydrogel sensor by heating, indicating that our chemical sensor could repeatably measure the target chemical substance for the long term. We believe that our structural-color biochemical sensor could be applied to various routine monitoring such as healthcare diagnosis and water safety.

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Stimuli-Responsive Structural Color Hydrogel Microbeads for Wearable Biometric Sensors

Tsuchiya M., Kurashina Y., Onoe H.

2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII （2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII）     2496 - 2499 2019年06月

ISSN  9781728120072

　概要を見る

© 2019 IEEE. This paper describes stimuli-responsive structural color hydrogel microbeads as sensing elements for wearable biometric sensors. Since the structural color with a curved surface has no angle dependency, spherical shape of microbeads is suitable for partial uses of structural color-based eye-recognizable sensors. As a first step for demonstrating our concept, we fabricated temperature responsive structural color hydrogel microbeads and confirmed those structural color clearly changed by the temperature change. These microbeads could be encapsulated in a wearable flexible device and the biological information could be properly measured from different viewing angles. We believe this wearable sensor with structural color microbeads could become an effective approach for sensing the environment and healthcare targets.

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Soft Spiral-Shaped Micro-Swimmer with Propulsion Force Control by Pitch Change

Yoshida K., Onoe H.

2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII （2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII）     217 - 220 2019年06月

ISSN  9781728120072

　概要を見る

© 2019 IEEE. This paper describes a soft spiral-shaped micro-swimmer with propulsion force controlled by pitch change. Soft spiral-shaped micro-swimmers, made of stimuli-responsive hydrogel encapsulating magnetic nanoparticles, were continuously formed by using a bevel-tip capillary. We achieved the pitch change of the double-layered micro-swimmer by temperature stimulus and confirmed that the propulsion force of the swimmer was controlled by the pitch change. We believe that our micro-swimmer could pave the way to various microscale biochemical applications such as autonomous soft-robots and soft micro-probes for intricate environment.

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Shape Deformation Analysis of Single Cell in 3d Tissue under Mechanical Stimuli

Kasahara K., Kurashina Y., Miura S., Miyata S., Onoe H.

2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII （2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII）     413 - 416 2019年06月

ISSN  9781728120072

　概要を見る

© 2019 IEEE. This paper describes an analytical platform to investigate the cell response against mechanical stimuli in in vitro 3D tissues. The system is capable of live-imaging cells in 3D tissues at a single cell level under mechanical stimuli, which makes this system similar to the in vivo environment and suitable for analysis of maturation mechanism. We succeeded in imaging various shapes of cells in 3D tissue under mechanical stimuli and observed that the stretch-induced deformation was distributed non-uniformly inside cells. We believe that our system could contribute to a further understanding of the tissue maturation mechanism induced by mechanical stimuli, which is highly useful for the development of tissue reconstruction.

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Multi-Hydrogel 4D Printing for Deformation Control

Uchida T., Onoe H.

2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII （2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII）     1780 - 1783 2019年06月

ISSN  9781728120072

　概要を見る

© 2019 IEEE. This paper describes a method to fabricate three-dimensional (3D) microstructures composed of multiple types of stimuli-responsive hydrogels. Using our method, multi-hydrogels 3D microstructures with internal gaps (ex. framed structure, beams structure etc.) can be printed and polymerized in supporting viscous liquid. We fabricated straight-line patterns composed of two types of hydrogels (pNIPAM: stimuli-responsive, and pAM: non-responsive). The printed multi-hydrogel structures were evaluated for the printing accuracy and the stimuli-responsivity to ensure their deformation controllability. Our proposed method would be an effective tool for creating multi-hydrogel 3D microstructures with various types of stimuli (optical, pH, molecular, etc.), for applications in soft actuators/robotics, and self-assembly/adaptive systems.

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Fabrication of metal microstructures in elastic hydrogel by multiphoton photoreduction

Terakawa M., Machida M., Onoe H., Niidome T., Heisterkamp A.

2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2019 （2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2019）  2019年06月

ISSN  9781728104690

　概要を見る

© 2019 IEEE. Soft materials, including elastic polymers and hydrogels, are promising materials for soft robots, implantable devices, and wearable devices owing to their flexibility and biocompatibility. In recent years, the scope of use of such soft materials is expanding further because of their integration with metal micro- and nanostructures, which exhibit attractive optical and electrical properties. In this study, we demonstrate the formation of metal microstructures inside a hydrogel by photoreduction of metal ion by using femtosecond laser. Because the hydrogels have permeability to fluids, metal ions are able to be added by simply immersing the hydrogel into the metal ion solution. Femtosecond laser pulses were focused and scanned in the hydrogel to fabricate metal microstructures [1, 2]. The optical diffraction pattern obtained with the silver grating inside the hydrogel showed spaced diffraction spots, which indicated that a regular, periodic silver grating was formed. Notably, the distance between the diffraction spots changed when the water content in the hydrogel was reduced. The grating period decreased when the hydrogel shrank owing to the loss of water (Fig. 1(a)), but the straight shapes of the line structures were preserved, which demonstrated the optical tunability of the fabricated structure.

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ECM-based Stretchable Microfluidic System for in vitro 3D Tissue Culture

Shimizu A., Goh W.H., Hashimoto M., Miura S., Onoe H.

2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII （2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII）     752 - 755 2019年06月

ISSN  9781728120072

　概要を見る

© 2019 IEEE. We present an extracellular matrix (ECM)-based stretchable microfluidic system for in vitro three-dimensional (3D) tissue culture, which mimics the in vivo blood vessels. The target cells (ex. endothelial cells (ECs)) can be cultured with perfusion and stretch simultaneously in our proposed system. Our ECM (collagen)-based microfluidic device was fabricated by dissolving water-soluble sacrificial molds fabricated with 3D printer. We demonstrated perfusion and stretch of collagen microfluidic devices with culturing human umbilical vein endothelial cells (HUVECs), showing that the cultured cells were stretched along the expansion of the collagen microchannel. We believe that our collagen-based microfluidic stretch system could be a useful tool for understanding the mechanisms of vascular tissue formation and mechanotransduction.

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Graphene-Based Wireless Inline Pressure Sensor for in Vivo Blood Pressure Monitoring

Inoue N., 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)）  2019-January   720 - 722 2019年01月

ISSN  9781728116105

　概要を見る

© 2019 IEEE. This study describes a graphene-based wireless inline pressure sensor that can be easily inserted between an implanted microdevice and a blood vessel for in vivo blood pressure monitoring. Our wireless pressure sensor is simply composed of a graphene sheet (piezo-resistive sensor) attached on a microfluidic elastic tube and a coil wound up to the tube as a transmitter. The applied pressure inside the tube can be monitored wirelessly by an external receiver coil. We fabricated the sensor system applicable to monitoring the range of typical blood pressure, 10-18 kPa, by designing the sensitivity depending on the stiffness and the thickness of the elastic tube, the turn numbers of the coils, and the distance between the coils. Furthermore, we demonstrated to wirelessly measure the blood-pressure-mimicking pulsed inputs with our sensor that was embedded in a biological tissue. We believe that our wireless inline pressure sensor could be an effective tool for monitoring in vivo implanted medical devices such as microfluidic artificial kidneys.

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Thin Layered Heterogeneous Vascularized 3D Tissue Models Constructed with Separated-Layer Collagen Microtube

Itai S., 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)）  2019-January   118 - 119 2019年01月

ISSN  9781728116105

　概要を見る

© 2019 IEEE. We present an in vitro vascularized 3D cell co-culture, performed by a separated-layer collagen microtube device. Our device can co-culture endothelial and other cells in close position, while the collagen layers are separated into an outer support layer and an inner culture layer. The close distance between different types of cells enhances mutual cell interaction and enables us to observe the tissue structures clearly. Moreover, while collagen tubes are directly attached to silicone tubes, perfusion culture is easily performed by an external pump system. We believe that our device could help the fabrication of various vascularized tissue models in high activity, and contribute to the development of pharmacokinetic testing platforms and regenerative medicine.

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Morphological Control of Endothelial Tube Formation by Three-Dimensional Lane-Shaped Patterns

Ikezawa Y., 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)）  2019-January   594 - 596 2019年01月

ISSN  9781728116105

　概要を見る

© 2019 IEEE. This paper describes an analytical platform to control endothelial tube formation by patterning cells and extracellular matrix (ECM) within 3D lane-shaped pattern. By using PDMS groove patterns (50-250\ \mu \mathrm{m} in width and height, several millimeters in length), human umbilical vein endothelial cells (HUVECs) were patterned three-dimensionally in collagen gel. The patterned HUVECs spontaneously form endothelial vascular tissues, but their morphologies can be controlled by the dimensions of patterns, cell densities, ECMs, etc. We succeeded in forming vascular tube tissues, and found that a number of branches of the vascular tissues depends on the dimensions of 3D-patterns. We believe that our culture system could be a useful tool for understanding the tube formation behavior of endothelial cells and for creating 3D-shape-controlled vascular tissues as a quantitative model in vitro.

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Hierarchical Hydrogel Drug Delivery System Enables Controlled Release of Adeno-Associated Viruses for Gene Therapy

Miyahara H., Kurashina Y., Ogawa Y., Kurihara A., Yoshida T., Okano H.J., Fujioka M., 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)）  2019-January   601 - 602 2019年01月

ISSN  9781728116105

　概要を見る

© 2019 IEEE. This paper describes a drug delivery system (DDS) to release Adeno-associated viruses (AAVs) for gene therapy. Our system has two-level hierarchical structures made of different hydrogel materials: (i) Calcium alginate hydrogel microparticles (\sim 100\ \mu \mathrm{m} in diameter) that can properly immobilize AAVs inside and release them for gene transfection triggered by enzymatic degradation, and (ii) a millimeter-scale collagen sheet that encapsulates those alginate microparticles with AAVs for stable fixation to even a tiny and complicated diseased site in our body, such as an inner ear for the treatment of hereditary hearing loss (Figure 1). We fabricated the AAVs-immobilized hydrogel microparticles and evaluated their AAV releasing functions by measured the gene transfection ratio to cultured HeLa cells. In addition, we also demonstrated that the controlled release of AAVs immobilized in the alginate microparticles embedded in the millimeter-scale collagen sheet can be externally triggered from the outside. We envision that our developed composite hydrogel DDS could be an essential and general tool for gene therapy in practical medical scenes, especially in the treatment at complicated internal sites.

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Eye-recognizable and repeatable biochemical flexible sensors using low angle-dependent photonic colloidal crystal hydrogel microbeads

Tsuchiya M., Kurashina Y., Onoe H.

Scientific Reports （Scientific Reports）  9 （ 1 ） 17059 2019年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2019, The Author(s). This paper presents eye-recognizable and repeatable biochemical flexible sensors using low angle-dependent stimuli-responsive photonic colloidal crystal hydrogel (PCCG) microbeads. Thanks to the stimuli-responsive PCCG microbeads exhibiting structural color, users can obtain sensing information without depending on the viewing angle and the mechanical deformation of the flexible sensor. Temperature-responsive PCCG microbeads and ethanol-responsive PCCG microbeads were fabricated from a pre-gel solution of N-isopropylacrylamide (NIPAM) and N-methylolacrylamide (NMAM) by using a centrifuge-based droplet shooting device (CDSD). As a proof-of-concept of thin and flexible biochemical sensors, temperature- and ethanol-sensing devices were demonstrated. By comparing the structural color of the stimuli-responsive PCCG microbeads and the color chart of the device, sensing information, including skin temperature of the human body and ethanol concentration in alcoholic beverages, was obtained successively. We expect that our device design using low angle-dependent stimuli-responsive PCCG microbeads would contribute to the development of user-friendly biochemical sensor devices for monitoring environmental and healthcare targets.

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Microfiber-shaped building-block tissues with endothelial networks for constructing macroscopic tissue assembly

Kurashina Y., Sato R., Onoe H.

APL Bioengineering （APL Bioengineering）  3 （ 4 ） 046101 2019年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2019 Author(s). We describe a microfiber-shaped hepatic tissue for in vitro macroscopic tissue assembly, fabricated using a double coaxial microfluidic device and composed of cocultured Hep-G2 cells and human umbilical vein endothelial cells (HUVECs). The appropriate coculture conditions for Hep-G2 cells and HUVECs in the microfiber-shaped tissue were optimized by changing the thickness of the core and the cell ratio. The HUVEC networks were formed in the microfiber-shaped tissue following culture for 3 days. Using this microfiber-shaped tissue as a building block, two types of macroscopic assembled tissues were constructed - parallel and reeled tissues. In both tissue types, the connection of the HUVEC network across the adjacent microfiber-shaped tissues was established after 2 days, because the calcium alginate shell of the microfiber-shaped tissue was enzymatically removed. Our approach could facilitate the generation of complex and heterogeneous macroscopic tissues mimicking the major organs including the liver, kidney, and heart for the treatment of critically ill patients.

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4D printing of multi-hydrogels using direct ink writing in a supporting viscous liquid

Uchida T., Onoe H.

Micromachines （Micromachines）  10 （ 7 ） 433 2019年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2019 by the authors. We propose a method to print four-dimensional (4D) stimuli-responsive hydrogel structures with internal gaps. Our 4D structures are fabricated by printing an N-isopropylacrylamide-based stimuli-responsive pre-gel solution (NIPAM-based ink) and an acrylamide-based non-responsive pre-gel solution (AAM-based ink) in a supporting viscous liquid (carboxymethyl cellulose solution) and by polymerizing the printed structures using ultraviolet (UV) light irradiation. First, the printed ink position and width were investigated by varying various parameters. The position of the printed ink changed according to physical characteristics of the ink and supporting liquid and printing conditions including the flow rates of the ink and the nozzle diameter, position, and speed. The width of the printed ink was mainly influenced by the ink flow rate and the nozzle speed. Next, we confirmed the polymerization of the printed ink in the supporting viscous liquid, as well as its responsivity to thermal stimulation. The degree of polymerization became smaller, as the interval time was longer after printing. The polymerized ink shrunk or swelled repeatedly according to thermal stimulation. In addition, printing multi-hydrogels was demonstrated by using a nozzle attached to a Y shape connector, and the responsivity of the multi-hydrogels to thermal-stimulation was investigated. The pattern of the multi-hydrogels structure and its responsivity to thermal-stimulation were controlled by the flow ratio of the inks. Finally, various 4D structures including a rounded pattern, a spiral shape pattern, a cross point, and a multi-hydrogel pattern were fabricated, and their deformations in response to the stimuli were demonstrated.

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Effect of cyclic stretch on tissue maturation in myoblast-laden hydrogel fibers

Bansai S., Morikura T., Onoe H., Miyata S.

Micromachines （Micromachines）  10 （ 6 ） 399 2019年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2019 by the authors. Engineering of the skeletal muscles has attracted attention for the restoration of damaged muscles from myopathy, injury, and extraction of malignant tumors. Reconstructing a three-dimensional muscle using living cells could be a promising approach. However, the regenerated tissue exhibits a weak construction force due to the insufficient tissue maturation. The purpose of this study is to establish the reconstruction system for the skeletal muscle. We used a cell-laden core-shell hydrogel microfiber as a three-dimensional culture to control the cellular orientation. Moreover, to mature the muscle tissue in the microfiber, we also developed a custom-made culture device for imposing cyclic stretch stimulation using a motorized stage and the fiber-grab system. As a result, the directions of the myotubes were oriented and the mature myotubes could be formed by cyclic stretch stimulation.

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Spatially-targeted laser fabrication of multi-metal microstructures inside a hydrogel

Machida M., Niidome T., Onoe H., Heisterkamp A., Terakawa M.

Optics Express （Optics Express）  27 （ 10 ） 14657 - 14666 2019年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement The spatially-targeted fabrication of bimetallic microstructures coexisting in the supporting hydrogel is demonstrated by multi-photon photoreduction. Microstructures composed of gold and silver were fabricated along a predefined trajectory by taking advantages of the hydrogel's ionic permeability. Different resonant wavelengths of optical absorption were obtained for gold, silver, and their bimetallic structures. Transmission electron microscopy and energy dispersive X-ray analysis revealed that the optical properties are attributable to the formation of bimetallic structure consisted of core-shell nanoparticles. The fabrication of dissimilar metal structures within hydrogel is a promising technique for optically driven actuators in soft robotics and sensing applications by allowing for site-selective optical properties.

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Graphene-based wireless tube-shaped pressure sensor for in vivo blood pressure monitoring

Inoue N., Koya Y., Miki N., Onoe H.

Micromachines （Micromachines）  10 （ 2 ） 139 2019年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2019 by the authors. We propose a wireless pressure sensor composed of a graphene sheet and a transmitter coil integrated with a polydimethylsiloxane (PDMS) tube. The pressure inside the tube was monitored wirelessly using an external receiver coil. We then monitored the typical blood pressure range, 12-20 kPa, using this fabricated sensor by changing the turn number of the receiver coil and the overlapping length of the coils. Furthermore, we demonstrated wireless blood pressure measurement by connecting our sensor to the blood vessel of a rat. Our results suggested that this sensor can be easily inserted between an implantable medical device and blood vessels for in vivo blood pressure monitoring. The proposed wireless pressure sensor could also be suitable for monitoring in vivo implanted medical systems, such as artificial organs and pump systems.

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Biohybrid device with antagonistic skeletal muscle tissue for measurement of contractile force

Morimoto Y., Onoe H., Takeuchi S.

Advanced Robotics （Advanced Robotics）  33 （ 5 ） 208 - 218 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  01691864

　概要を見る

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group and The Robotics Society of Japan. This paper describes a fabrication method and driving property of a biohybrid device with an antagonistic pair of skeletal muscle tissues and a flexible substrate. Since two skeletal muscle tissues are symmetrically arranged with the flexible substrate as the central axis, the flexible substrate deforms according to differences in their tension. In the formation of the antagonistic pair of skeletal muscle tissues, we assembled myoblast-laden hydrogel sheets and cultured them to construct a single skeletal muscle tissue on each side of the flexible substrate. We confirmed that the skeletal muscle tissue on the flexible substrate had the fundamental morphology and function of skeletal muscle. Furthermore, we made the biohybrid device actuate with deformation of the flexible substrate by selective contractions of the skeletal muscle tissues. From the deformation of the flexible substrate, we estimated the contractile force of each skeletal muscle tissue in the biohybrid device using finite element analysis. This biohybrid device, composed of an antagonistic pair of skeletal muscle tissues and a flexible substrate, can potentially be used in biological studies and pharmacokinetic assays involving the antagonistic pair of skeletal muscles.

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Double-layer perfusable collagen microtube device for heterogeneous cell culture

Itai S., Tajima H., Onoe H.

Biofabrication （Biofabrication）  11 （ 1 ） 0150110 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  17585082

　概要を見る

© 2018 IOP Publishing Ltd. In vitro perfusable 3D tissue models mimic in vivo tissues and have several benefits in drug testing. However, processes used to fabricate these models often tend to be complicated. Here, we present a double-layer perfusable collagen tube device for multilayered in vitro 3D cell culture. The device is simply made by the repetition of a molding process. The thicknesses of the collagen layers in the tube device can be flexibly designed, and heterogeneous cell types can be co-cultured in/on each collagen layer. Moreover, while our collagen tube is directly attached to silicone tubes, the collagen tube can easily be connected to an external pump system for perfusion culture. We fabricated six different sizes of collagen devices (inner diameter approximately 300-1000 μm) using different molds, and successfully controlled the coefficients of variation to be below 5% for the diameters of each layer for all six device sizes. The device is strong enough to manipulate with tweezers, and can remain stable for more than 3 months in a medium. For the cell culture, we successfully and correctly encapsulated cells in the layer shape at the desired position, and confirmed cell migration. Using the perfusion culture, we demonstrated that the alignments of the HUVEC actin filaments become parallel to the flow direction. We believe that our device could advance the easy fabrication of various tissue models (that is, models mimicking in vivo tissues). In particular, the device could help fabricate vascularized tissue models, and contribute to the development of pharmacokinetic testing platforms and regenerative medicine.

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Multipoint bending and shape retention of a pneumatic bending actuator by a variable stiffness endoskeleton

Shotaro Yoshida, Yuya Morimoto, Lanying Zheng, Hiroaki Onoe, Shoji Takeuchi

Soft Robotics 5   718 - 7252 2019年

研究論文（学術雑誌）, 共著, 査読有り

Phase-separated core-shell hydrogel microbeads from homogeneous mixed polymer solution by simultaneous gelation

Kurashina Y., Tsuchiya M., Kasahara K., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     910 - 911 2019年

ISSN  9781733419000

　概要を見る

© 2019 CBMS-0001. We propose a generation method of the hydrogel microbeads with the core-shell structure based on phase separation of homogeneous polymer solution mixed with sodium alginate and N-isopropylacrylamide (NIPAM). Without using oil phase and tubing/pumping apparatus, centrifugally generated microdroplets of photocrosslinkable monomer solution can be polymerized by UV irradiation with the assistant of ionic gelation of alginate hydrogel. By using the centrifugal microfluidic device with UV LEDs, the homogeneous mixed polymer solution was successfully turned into hydrogel microbeads with the phase-separated core-shell structure with simultaneous photo-polymerization and ionic crosslink. We envision that our proposed core-shell hydrogel microbeads would be useful tools for functional drug delivery systems and health monitoring biochemical sensors for in vivo applications.

Fabrication of metal microstructures in elastic hydrogel by multiphoton photoreduction

Terakawa M., Machida M., Onoe H., Niidome T., Heisterkamp A.

Optics InfoBase Conference Papers （Optics InfoBase Conference Papers）  Part F140-CLEO_Europe 2019 2019年

ISSN  9781557528209

　概要を見る

© 2019 IEEE Soft materials, including elastic polymers and hydrogels, are promising materials for soft robots, implantable devices, and wearable devices owing to their flexibility and biocompatibility. In recent years, the scope of use of such soft materials is expanding further because of their integration with metal micro- and nanostructures, which exhibit attractive optical and electrical properties. In this study, we demonstrate the formation of metal microstructures inside a hydrogel by photoreduction of metal ion by using femtosecond laser. Because the hydrogels have permeability to fluids, metal ions are able to be added by simply immersing the hydrogel into the metal ion solution. Femtosecond laser pulses were focused and scanned in the hydrogel to fabricate metal microstructures [1, 2]. The optical diffraction pattern obtained with the silver grating inside the hydrogel showed spaced diffraction spots, which indicated that a regular, periodic silver grating was formed. Notably, the distance between the diffraction spots changed when the water content in the hydrogel was reduced. The grating period decreased when the hydrogel shrank owing to the loss of water (Fig. 1(a)), but the straight shapes of the line structures were preserved, which demonstrated the optical tunability of the fabricated structure.

Assembly of actomyosin bundles in microfluidic channel

Kawara S., Hiratsuka Y., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     209 - 210 2019年

ISSN  9781733419000

　概要を見る

Artificial reconstruction of a highly aligned actomyosin bundle utilizing a laminar-flow microfluidic device enables the fabrication of a bio-actuator mimicking skeletal muscle. At the boundary of two fluid streams involving fibrous myosinⅡ and actin macromolecules respectively, actomyosin bundles are spontaneously assembled and aligned along with the flow direction. We successfully obtained several millimeter-scale actomyosin bundles from the microfluidic devices and also revealed that the actin filament was highly aligned in the bundle, which could enhance the mechanical force produced by contraction. We conceive that our methodology for the assembly of actomyosin bundle would contribute to the development of bio-actuators and furthermore to the understanding of the self-organization mechanism and the mechanical characteristics.

Ultrasound-triggered controlled release of nanoparticles from hydrogel microbeads by release-promoting particles

Kubota T., Kurashina Y., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     756 - 757 2019年

ISSN  9781733419000

　概要を見る

We propose an ultrasound-triggered drug delivery system (DDS) with release promoting particles for long-term controlled drug release with low power ultrasound. By using a centrifugal fluidic device, we fabricated calcium alginate hydrogel microbeads containing fluorescent silica nano-particles as a drug model and tungsten micro-particles for promoting release. The silica nano-beads were efficiently released from the microbeads by the ultrasound because the tungsten micro-particles can receive the energy of the applied ultrasound. This ultrasound method will be a key technology of DDS for control of drug release with less burden on the patients.

Surface tension driven swarm robots for emerging coordinating motions

Yoshida K., Hayashi T., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     1220 - 1221 2019年

ISSN  9781733419000

　概要を見る

This paper describes surface tension driven swarm robots for emerging various coordinate motions. Swarm robots that can swim driven by Marangoni effect are self-assembled by surface tension at air-liquid interface and are loosely coupled, ensuring that the swarm robots have the robustness of total swarm system. Even if large external disturbance is applied, the swarm robots separate to protect the total system and continue swimming. Furthermore, the active robot can rescue a stopped robot by self-assembly, and combination task is also exhibited. We believe that our proposed surface tension driven swarm robots will be a powerful approach to the various biochemical application including highly robust swarm robots and models to mimic biological organisms.

Stretching motion-driven ECM-based pulsatile flow generator for mimicking venous blood flow in vivo

Shimizu A., Goh W.H., Itai S., Hashimoto M., Miura S., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     314 - 315 2019年

ISSN  9781733419000

　概要を見る

We present a pulsatile flow generator with an extracellular matrix (ECM)-based microfluidic device for mimicking venous blood flow in vivo. The pulsatile flow can be generated by directly stretching the ECM channel with stepping motors, imitating in vivo veins compressed by surrounding muscles. The flow velocity was estimated by the theoretical calculation based on finite element simulation. Moreover, vein endothelial cells were cultured in our device with fluidic shear stress and stretch stress simultaneously.

Rapid stimuli-responsivity of hydrogel microfiber actuator with surface porous structure

Karube M., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     1186 - 1187 2019年

ISSN  9781733419000

　概要を見る

This paper describes a stimuli-responsive microfiber-shaped hydrogel actuator with a porous surface layer. By using cellulose nanofibers as a sacrificial template material, we formed nanoscale pores on the surface of the microfiber in gentle condition, enabling the rapid response to external stimuli because the formed nanopores can work as pathways of fluid between inside and outside of the microfiber. We analyzed the formed nanopores by scanning electron microscope (SEM) and confirmed that the nanoporous hydrogel micro-actuator responded faster than the non-porous one. Our cellulose nanofiber-based nanoporous forming approach could be widely applied to polymer-based soft robotics and biomedical soft actuators because of its gentle and biocompatible processes.

Metal wiring on flexible origami structure for stable resistance value against deformation

Uchida T., Yasuga H., Iwase E., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     201 - 202 2019年

ISSN  9781733419000

　概要を見る

This paper describes a new approach to fabricate a flexible circuit that has stable electric resistance value against deformation. The flexible circuit is fabricated by depositing metal wiring on a folded flexible origami structure. We confirmed that the resistance value of the metal wiring on the origami structure was stable against stretching and bending compared to that of the wiring formed on a simple elastic flexible sheet. Using this origami structure, we demonstrated a simple wearable device that fits a wrist. We believe that this origami-based flexible device could be a one possible route to robust and stable wearable devices that can be freely and largely expanded.

Detection of swell/shrink behavior of stimuli-responsive hydrogel by single walled carbon nanotube strain sensor

Iyama E., Kiriya D., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     1332 - 1333 2019年

ISSN  9781733419000

　概要を見る

In this research, we propose a method to detect the swell/shrink behavior of stimuli-responsive hydrogel by a strain sensor. The strain sensor is composed of single walled carbon nanotubes (SWCNTs) and a flexible sheet. By integrating the SWCNT strain sensor with a stimuli-responsible hydrogel, the swell/shrink behavior of the hydrogel can be simply sensed as an electrical resistance change of the SWCNT strain sensor. Our approach could contribute to simplify the stimulus detection and could be effective for the integration of high-sensitive chemical sensors with electrical devices.

Cell-encapsulating chitosan-collagen hybrid hydrogel conduit for peripheral nerve regeneration

Itai S., Suzuki K., Kurashina Y., Kimura H., Amemiya T., Sato K., Nakamura M., Onoe H.

23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019 （23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019）     880 - 881 2019年

ISSN  9781733419000

　概要を見る

This paper presents a tube-shaped chitosan-collagen hydrogel conduit containing cells for peripheral nerve regeneration. The conduit is simply made by molding, and composed of two layers: A chitosan layer strengthens the conduit mechanically, and a collagen layer provides a scaffold for cells supporting the axonal extension. By using our conduit, peripheral nerves could be regenerated in high quality, because those encapsulated cells release paracrine factors including nerve growth factors (NGF) and supply good environments for nerve tissue reconstruction. We examined the biocompatibility and bioabsorbability of our conduit, and the results represent that our device induced the extension of neurites of neural model cells and was dissolved away in specific terms. We believe this conduit will become a cutting-edge conduit for peripheral nerve surgeries.

Spring-shaped stimuli-responsive hydrogel actuator for magnifying compression and expansion motions

Yoshida K., Nakajima S., Kawano R., 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)）  2018-January   579 - 580 2018年04月

ISSN  9781538647820

　概要を見る

© 2018 IEEE. This study describes stimuli-responsive hydrogel micro-actuators for compressive/expanding actuation of stimuli-responsive hydrogels. Inspired by living bioactuators such as a stalk in vorticella, we applied this spring-shaped structure to engineered stimuli-responsive hydrogel actuators to magnify its degree of deformation. We achieved the shrinkage degree of ∼0.2, which is the approximately 2 time smaller than that of bulk hydrogel material (shrinkage degree ∼0.4), without any modification of molecules. Furthermore, both compression and expansion motions were demonstrated by changing the pattern of stimuli-responsive part in the microsprings, indicating that our approach could enable wide variety of motions by their patterning condition of microsprings. Our large compression/expansion stimuli-responsive hydrogel microsprings have immense potential to be applied in various microengineering products including soft actuators, chemical sensors, and medical applications.

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Triple-coaxial flow for continuous production of microtubes containing microbes for bioremediation

Fujimoto K., Higashi K., Onoe H., Miki N.

Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS) （Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)）  2018-January   1269 - 1271 2018年04月

ISSN  9781538647820

　概要を見る

© 2018 IEEE. This paper describes a microfluidic device to continuously produce a hydrogel microtube using triple-coaxial flow. In our prior work, double-coaxial flow was used to produce hydrogel microtubes, though continuous and mass production was a challenge. In this work, we also demonstrate bioremediation using the microtubes that encapsulate microbial suspension. The microenvironment created by the microtubes enabled efficient purification of aqueous sample solution and in addition, the microbes are maintained inside the microtube and are easily collected without contaminating the solution. The proposed technology can be applied to any types of microbes and can be of great benefit for various microbial processes.

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Hydrogel microfibers for biochemical applications

Onoe H.

MHS 2017 - 28th 2017 International Symposium on Micro-NanoMechatronics and Human Science （MHS 2017 - 28th 2017 International Symposium on Micro-NanoMechatronics and Human Science）  2018-January   1 - 2 2018年02月

ISSN  9781538633144

　概要を見る

© 2017 IEEE. This paper describes fabrication and applications of stimuli-responsive hydrogel microfibers for biochemical sensors and actuators. Our group has developed stimuli-responsive hydrogel microsprings (SR springs) for mugnifying the shrink/swell movements. The SR springs, made of composite hydrogel of p(NIPAM-co-AAc) and calcium alginate, were continuously formed by using a bevel-tip capillary. By stimulating single-layered or patterned SR springs, we achieved to magnify the shrink/swell movements and to control the direction of the movements.

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Graphene-based inline pressure sensor integrated with microfluidic elastic tube

Inoue N., Onoe H.

Journal of Micromechanics and Microengineering （Journal of Micromechanics and Microengineering）  28 （ 014001 ）  2018年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09601317

　概要を見る

© 2017 IOP Publishing Ltd. We propose an inline pressure sensor composed of a polydimethylsiloxane (PDMS) microfluidic tube integrated with graphene sheets. The PDMS tube was fabricated through molding, and a multilayered graphene sheet was transferred on the surface of the PDMS tube. The pressure inside the tube was monitored using the changes in the electrical resistance of the transferred graphene. The proposed pressure sensor could be suitable for precise pressure measurement for a small amount of fluid in microfluidic systems including organ-on-a-chip devices.

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Spring constant measurement using a MEMS force and displacement sensor utilizing paralleled piezoresistive cantilevers

Kohyama S., Takahashi H., Yoshida S., Onoe H., Hirayama-Shoji K., Tsukagoshi T., Takahata T., Shimoyama I.

Journal of Micromechanics and Microengineering （Journal of Micromechanics and Microengineering）  28 （ 045013 ）  2018年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09601317

　概要を見る

© 2018 IOP Publishing Ltd. This paper reports on a method to measure a spring constant on site using a micro electro mechanical systems (MEMS) force and displacement sensor. The proposed sensor consists of a force-sensing cantilever and a displacement-sensing cantilever. Each cantilever is composed of two beams with a piezoresistor on the sidewall for measuring the in-plane lateral directional force and displacement. The force resolution and displacement resolution of the fabricated sensor were less than 0.8 μN and 0.1 μm, respectively. We measured the spring constants of two types of hydrogel microparticles to demonstrate the effectiveness of the proposed sensor, with values of approximately 4.3 N m-1 and 15.1 N m-1 obtained. The results indicated that the proposed sensor is effective for on-site spring constant measurement.

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Differentiation of 3D-shape-controlled mouse neural stem cell to neural tissues in closed agarose microchambers

Matsushiro Y., Kato-Negishi M., Onoe H.

Biotechnology and Bioengineering （Biotechnology and Bioengineering）  115 （ 6 ） 1614 - 1623 2018年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00063592

　概要を見る

© 2018 Wiley Periodicals, Inc. This paper describes three-dimensional (3D) tissue shape control of mouse neural stem cell (mNSC) micro tissues by using closed agarose microchambers for effective differentiation induction of neurons in vitro. Our agarose microchambers, made by micromolding, can be sealed with an agarose sheet to form the mNSC tissues along the shape of microchambers. We constructed lane-shaped mNSC tissues with different width (∼60–210 μm) and thickness (∼25–95 μm) dimensions and induced differentiation to neurons with differentiation medium. We found that in thick tissues (thickness: >60 μm), distribution of differentiated neurons was not uniform, whereas in thin tissues (thickness: ∼30 μm), differentiated neurons were uniformly distributed with high differentiation efficiency. Our system to construct in vitro 3D neural tissues having uniformly distributed neurons at high differentiation ratio, could become an effective tool for drug screening using 3D neural tissues and 3D mNSC tissues under differentiation induction.

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Development of a triple-coaxial flow device for fabricating a hydrogel microtube and its application to bioremediation

Fujimoto K., Higashi K., Onoe H., Miki N.

Micromachines （Micromachines）  9 （ 76 ）  2018年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2018 by the authors. This paper demonstrates a triple-coaxial flow device to continuously produce a hydrogel microtube using a microfluidic technique. The hydrogel microtube can encapsulate a microbial suspension, while allowing the diffusion of oxygen and nutrients into the microtube and preventing microbes from passing into or out of the microtube. The microtubes also enable the collection of the microbes after task completion without contaminating the environment. In our previous study, we used a double-coaxial flow device to produce the microtubes, but continuous production was a challenge. In the present study, we developed a microfluidic device that fabricates a triple-coaxial flow to enable continuous production of the microtubes. Here, we characterize the production capacity of the microtubes along with their properties and demonstrate bioremediation using microtubes encapsulating a microbial suspension.

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Origami-based self-folding of co-cultured NIH/3T3 and HepG2 cells into 3D microstructures

He Q., Okajima T., Onoe H., Subagyo A., Sueoka K., Kuribayashi-Shigetomi K.

Scientific Reports （Scientific Reports）  8 （ 4556 ）  2018年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2018 The Author(s). This paper describes an origami-inspired self-folding method to form three-dimensional (3D) microstructures of co-cultured cells. After a confluent monolayer of fibroblasts (NIH/3T3 cells) with loaded hepatocytes (HepG2 cells) was cultured onto two-dimensional (2D) microplates, degradation of the alginate sacrificial layer in the system by addition of alginate lyase triggered NIH/3T3 cells to self-fold the microplates around HepG2 cells, and then 3D cell co-culture microstructures were spontaneously formed. Using this method, we can create a large number of 3D cell co-culture microstructures swiftly with ease in the same time. We find that HepG2 cells confined in the 3D cell co-culture microstructures have an ability to enhance the secreted albumin compared to 2D system in a long culture period. The result indicates that the origami-based cell self-folding technique presented here is useful in regenerative medicine and the preclinical stage of drug development.

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Microfluidic-based flexible reflective multicolor display

Kobayashi K., Onoe H.

Microsystems and Nanoengineering （Microsystems and Nanoengineering）  4 （ 17 ）  2018年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2018 The Author(s). This paper describes a microfluidic-based flexible reflective display constructed using dyed water droplets and air gaps as pixel elements. Our display is composed of a flexible polydimethylsiloxane sheet with a connected pixel-patterned microchannel. Several types of dyed water droplets and air gaps are sequentially introduced to the microchannel through a suction process to display a multicolor image. The displayed image is stable and can be retained without an energy supply. To ensure that images are displayed correctly, the geometric parameters of the dot pixel design and minimum differential pressure necessary to drive the water droplets are evaluated. As a demonstration, we successfully display three-color dot-matrix reflective images and bitmap characters in the microchannel. Our proposed method can be applied to energy-less and color-changeable displays for use in future daily-life accessories, such as bags, shoes, and clothes, and can change the surface color and pattern of these accessories.

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Biohybrid robot powered by an antagonistic pair of skeletal muscle tissues

Morimoto Y., Onoe H., Takeuchi S.

Science Robotics （Science Robotics）  3 （ eaat4440 ）  2018年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

Copyright © 2018 The Authors, some rights reserved. Biohybrid robots are attracting attention as promising candidates to enhance robot applicability to studies on biological designs and in vitro construction of biological dynamic systems. Rapid progress in biohybrid robots with skeletal muscle tissues formed on a flexible substrate has enabled various types of locomotion powered by muscle tissue. However, it has been difficult to achieve high levels of both large and long-Term actuations of the skeletal muscle tissues because of their spontaneous shrinkage through the course of the tissue culture. To overcome this limitation, we adapted the concept of biological systems and developed a biohybrid robot actuated by an antagonistic pair of skeletal muscle tissues. Our robot achieved large actuation (∼90° of rotation of a joint) by selective contractions of the skeletal muscle tissues and a long lifetime (∼1 week) by balancing tensions of the antagonistic tissues to prevent the spontaneous shrinkage. As a demonstration, we showed that our biohybrid robots allowed a pick-And-place manipulation of objects. This research may provide a platform to exceed the limitations of design in conventional biohybrid robots and replicate various lifelike movements.

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Spring-shaped stimuli-responsive hydrogel actuator with large deformation

Yoshida K., Nakajima S., Kawano R., Onoe H.

Sensors and Actuators, B: Chemical （Sensors and Actuators, B: Chemical）  272   361 - 368 2018年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09254005

　概要を見る

© 2018 Elsevier B.V. This study describes a novel microfluidics-based method for compressive/expanding actuation of stimuli-responsive hydrogel microsprings with large deformations. A continuous flow of mixed alginate and poly(N-isopropylacrylamide-co-acrylic acid) pre-gel solution can spontaneously form a hydrogel microspring with a wide range of gradient pitches via buoyancy force. This technique enables fabrication of hydrogel microsprings using only simple capillaries and syringe pumps. The resulting microsprings can be patterned via laminar flow inside the capillary, which can contribute to large deformation. Single-layered hydrogel microsprings shrunk isotropically while maintaining the shape of the spring. Compressing stimuli-responsive microsprings can be done by patterning the shrinking part of the spring. Here, the degree of compression in the double-layered spring depends on the initial pitch. Furthermore, large axial expansion of microsprings can be achieved by shrinking part of a microspring. Our large compression/expansion stimuli-responsive hydrogel microsprings have immense potential to be applied in various microengineering products including soft actuators, chemical sensors, and medical applications.

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Multipoint bending and shape retention of a pneumatic bending actuator by a variable stiffness endoskeleton

Shotaro Yoshida, Yuya Morimoto, Lanying Zheng, Hiroaki Onoe, Shoji Takeuchi

Soft Robotics 2018年

研究論文（学術雑誌）, 共著, 査読有り

Controlled construction of stable network structure composed of honeycomb-shaped microhydrogels

Hayakawa M., Umeyama S., Nagai K., Onoe H., Takinoue M.

Life （Life）  8 （ 38 ）  2018年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Recently, the construction of models for multicellular systems such as tissues has been attracting great interest. These model systems are expected to reproduce a cell communication network and provide insight into complicated functions in living systems./Such network structures have mainly been modelled using a droplet and a vesicle. However, in the droplet and vesicle network, there are difficulties attributed to structural instabilities due to external stimuli and perturbations. Thus, the fabrication of a network composed of a stable component such as hydrogel is desired. In this article, the construction of a stable network composed of honeycomb-shaped microhydrogels is described. We produced the microhydrogel network using a centrifugal microfluidic technique and a photosensitive polymer. In the network, densely packed honeycomb-shaped microhydrogels were observed. Additionally, we successfully controlled the degree of packing of microhydrogels in the network by changing the centrifugal force. We believe that our stable network will contribute to the study of cell communication in multicellular systems.

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Direct writing of 3D stimuli-responsive hydrogel microstructures in supporting viscous liquid

Uchida T., Onoe H.

22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018 （22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018）  1   528 - 529 2018年

ISSN  9781510897571

　概要を見る

Copyright© (2018) by Chemical and Biological Microsystems Society.All rights reserved. This paper describes a novel method to fabricate three-dimensional (3D) structures composed of a stimuli-responsive hydrogel. Using this method, 3D structures with internal gaps (ex. framed structure, hangout structure etc.) can be printed directly in supporting viscous liquid and polymerized with ultraviolet (UV) irradiation. We confirmed that the fabricated 3D microstructures with internal gaps successfully changed their shapes by external stimuli such as temperature. Our proposed method would be an effective tool for creating hydrogel 3D microstructures with various types of stimuli (optical, pH, molecular, etc.), for applications in soft actuators/robotics, and self-assembly/adaptive systems.

Photopolymerized hydrogel microbeads generated by simultaneous UV irradiation with centrifuge

Kurashina Y., Onoe H.

22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018 （22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018）  1   547 - 548 2018年

ISSN  9781510897571

　概要を見る

Copyright© (2018) by Chemical and Biological Microsystems Society.All rights reserved. We propose a method to fabricate photopolymerized hydrogel microbeads using UV irradiation with centrifuge-based particle generation. Without using oil phase and tubing/pumping apparatus, centrifugally generated microdroplets of photo-crosslinkable monomer solution can be polymerized by UV irradiation with the assistant of ionic gelation of alginate hydrogel. We developed the centrifugal microfluidic device with UV LEDs, demonstrated the generation of hydrogel microbeads composed of poly(N-isopropylacrylamide) (pNiPAM) and calcium alginate, and confirmed thermal responsivity of fabricated pNiPAM/alginate hydrogel microbeads. We envision that our proposed method would be useful for generating functional hydrogel microbeads for drug delivery systems and health monitoring biochemical sensors for in vivo applications.

Microfluidically Patterned Dome-Shaped Photonic Colloidal Crystals Exhibiting Structural Colors with Low Angle Dependency

Noriyuki Suzuki, Eiji Iwase, Hiroaki Onoe

Advanced Optical Materials 5   1600900 2017年

研究論文（学術雑誌）, 共著, 査読有り

Flexible Coloring Element by Using Bending Defromation of Electroactive Hydrogel

KodaiUsuki, Hiroaki Onoe, Eiji Iwase

Electonics and Communications in Japan 100 （ 1 ） 44 - 48 2017年

研究論文（学術雑誌）, 共著, 査読有り

Micro-tube mass production device for microbial culture

Kazuma Fujimoto, Kazuhiko Higashi, Hiroaki Onoe, Norihisa Miki

Japanese Journal of Applied Physics 2017年

研究論文（学術雑誌）, 共著, 査読有り

Liquid-filled Flexible Micro Suction-Controller Array for Enhanced Robotic Object Manipulation

Satoshi Nishita, Hiroaki Onoe

Journal of Microelectromechanical Systems 26   366 - 375 2017年

研究論文（学術雑誌）, 共著, 査読有り

Twisting microfluidics in a planetary centrifuge

Shoya Yasuda, Masayuki Hayakawa, Hiroaki Onoe, Masahiro Takinoue

Soft Matter 13   2141 - 2147 2017年

研究論文（学術雑誌）, 査読有り

Compartmentalized spherical collagen microparticles for anisotropic cell culture microenvironments

Satoru Yoshida, Masahiro Takinoue, Hiroaki Onoe

Advanced Healthcare Material 6   1601463 2017年

研究論文（学術雑誌）, 共著, 査読有り

Functionalized core-shell hydrogel microsprings by anisotropic gelation with bevel-tip capillary

3. Koki Yoshida, Hiroaki Onoe

Scientific Reports 7   45987 2017年

研究論文（学術雑誌）, 共著, 査読有り

Rod-shaped neural units for aligned 3D neural network connection

Midori Kato-Negishi, Hiroaki Onoe, Akane Itou, Shoji Takeuchi

Advanced Healthcare Materials, 6 （ 1700143 ）  2017年

研究論文（学術雑誌）, 共著, 査読有り

Stimuli-responsive hydrogel microfibers with controlled anisotropic shrinkage and cross-sectional geometries

Shunsuke Nakajima, Ryuji Kawano, Hiroaki Onoe

Soft Matter 13   3710 - 3719 2017年

研究論文（学術雑誌）, 共著, 査読有り

Micropatterning of multiple photonic colloidal crystal gels for flexible structural color films

Noriyuki Suzuki, Eiji Iwase, Hiroaki Onoe

Langmuir 33   6102 - 6107 2017年

研究論文（学術雑誌）, 共著, 査読有り

Hollow hydrogel microfiber encapsulating microorganisms for mass-cultivation in open systems

Kazuhiko Higashi, Miho Ogawa, Kazuma Fujimoto, Hiroaki Onoe, Norihisa Miki

Micromachines 8 （ 176 ）  2017年

研究論文（学術雑誌）, 共著, 査読有り

Capillary-based Centrifugal Microfluidic Device for Size-controllable Formation of Monodisperse Microdroplets

Masamune Morita, Hitoyoshi Yamashita, Masayuki Hayakawa, Hiroaki Onoe, Masahiro Takinoue

Journal of Visualized Experiments 108   e53860 2016年02月

研究論文（学術雑誌）, 共著, 査読有り

Complex-shaped three-dimensional multi-compartmental microparticles generated by diffusional and Marangoni microflows in centrifugally discharged droplets

Masayuki Hayakawa, Hiroaki Onoe, Ken H. Nagai, Masahiro Takinoue

Scientific Reports 6   20793 2016年02月

研究論文（学術雑誌）, 査読有り

Differentiation Induction of Mouse Neural Stem Cells in Hydrogel Tubular Microenvironment with Controlled Tube Dimensions

Hiroaki Onoe, Midori Kato-Negishi, Akane Itou, Shoji Takeuchi

Advanced Healthcare Materials 5 （ 9 ） 1104 - 1111 2016年

研究論文（学術雑誌）, 共著, 査読有り

竹槍状微細管を用いたハイドロゲルマイクロスプリングの構築とアクチュエータへの応用

吉田光輝, 尾上弘晃

電気学会論文誌E 136 （ 9 ） 198 - 403 2016年

研究論文（学術雑誌）, 共著, 査読有り

High-Resolution Vertical Observation of Intracellular Structure using Magnetically Responsive Microplates

Tetsuhiko Teshima, Hiroaki Onoe, Soichiro Tottori, Hiroka Aonuma, Takeomi Mizutani, Koki Kamiya, Hirotaka Ishihara, Hirotaka Kanuka, Shoji Takeuchi

Small 12 （ 25 ） 3366 - 3373 2016年

研究論文（学術雑誌）, 共著, 査読有り

Dynamic transformation of self-assembled structures using anisotropic magnetized hydrogel microparticles

Satoru Yoshida, Masahiro Takinoue, Eiji Iwase,Hiroaki Onoe

Journal of Applied Physics 120   084905 2016年

研究論文（学術雑誌）, 共著, 査読有り

Analyses of the influence of asymmetric and fluctuating driving forceson propeller-shaped catalytic micromotors

Masayuki Hayakawa, Hiroaki Onoe, Ken H. Nagai, Masahiro Takinoue

Micromachines 7 （ 227 ）  2016年

研究論文（学術雑誌）, 共著, 査読有り

電場応答性ハイドロゲルの屈曲変形を利用した柔軟発色素子

薄功大, 尾上弘晃, 岩瀬英治

電気学会誌E部門 135 （ 12 ） 480 - 483 2015年12月

研究論文（学術雑誌）, 共著, 査読有り

Observation and manipulation of a capillary jet in a centrifuge-based droplet shooting device

Kazuki Maeda, Hiroaki Onoe, Masahiro Takinoue, Shoji Takeuchi

Micromachines 6 （ 10 ） 1526 - 1533 2015年10月

研究論文（学術雑誌）, 共著, 査読有り

Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model

Keiko Sugai, Soraya Nishimura, Midori Kato-Negishi, Hiroaki Onoe, Shintaroh Iwanaga, Yoshiaki Toyama, Morio Matsumoto, Shoji Takeuchi, Hideyuki Okano, Masaya Nakamura

Journal of Neuroscience Research 93 （ 12 ） 1826 - 1838 2015年08月

研究論文（学術雑誌）, 共著, 査読有り

Droplet-Shooting and Size-Filtration (DSSF) Method for Synthesis of Cell-Sized Liposomes with Controlled Lipid Compositions

Masamune Morita, Hiroaki Onoe, Miho Yanagisawa, Hiroaki Ito, Masatoshi Ichikawa, Kei Fujiwara, Hirohide Saito, Masahiro Takinoue

ChemBioChem 16 （ 14 ） 2029 - 2035 2015年08月

研究論文（学術雑誌）, 共著, 査読有り

Deformable coloring element using an electroactive hydrogel with the bottom arrangement of electrodes

Kodai Usuki, Hiroaki Onoe, Eiji Iwase

Japanese Journal of Applied Physics 56   06FP06 2015年04月

研究論文（学術雑誌）, 共著, 査読有り

Generation of monodisperse cell-sized microdroplets using a centrifuge-based axisymmetric co-flowing microfluidic device

Hitoyoshi Yamashita, Masamune Morita, Haruka Sugiura, Kei Fujiwara, Hiroaki Onoe, Masahiro Takinoue

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 119 （ 4 ） 492 - 495 2015年04月

研究論文（学術雑誌）, 共著, 査読有り

Liquid-filled tunable lenticular lens

Iimura, Yoshinobu, Onoe, Hiroaki, Teshima, Tetsuhiko, Heo, Yun Jung, Yoshida, Shotaro, Morimoto, Yuya, Takeuchi, Shoji

JOURNAL OF MICROMECHANICS AND MICROENGINEERING 25 （ 3 ） 236 - 246 2015年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0960-1317

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Smooth Muscle-Like Tissue Constructs with Circumferentially Oriented Cells Formed by the Cell Fiber Technology

Hsiao, Amy Y., Okitsu, Teru, Onoe, Hiroaki, Kiyosawa, Mahiro, Teramae, Hiroki, Iwanaga, Shintaroh, Kazama, Tomohiko, Matsumoto, Taro, Takeuchi, Shoji

PLOS ONE 10 （ 3 ）  2015年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1932-6203

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Cell-laden microfibers for bottom-up tissue engineering

Onoe, Hiroaki, Takeuchi, Shoji

DRUG DISCOVERY TODAY 20 （ 2 ） 236 - 246 2015年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1359-6446

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Magnetically Responsive Microflaps Reveal Cell Membrane Boundaries from Multiple Angles

Teshima, Tetsuhiko, Onoe, Hiroaki, Aonuma, Hiroka, Kuribayashi-Shigetomi, Kaori, Kamiya, Koki, Tonooka, Taishi, Kanuka, Hirotaka, Takeuchi, Shoji

ADVANCED MATERIALS 26 （ 18 ） 2850 - 2856 2014年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0935-9648

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Parylene Mobile Microplates Integrated with an Enzymatic Release for Handling of Single Adherent Cells

Teshima, Tetsuhiko, Onoe, Hiroaki, Kuribayashi-Shigetomi, Kaori, Aonuma, Hiroka, Kamiya, Koki, Ishihara, Hirotaka, Kanuka, Hirotaka, Takeuchi, Shoji

SMALL 10 （ 5 ） 912 - 921 2014年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1613-6810

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Centrifuge-based cell encapsulation in hydrogel microbeads using sub-microliter sample solution

Onoe, Hiroaki, Inamori, Kiichi, Takinouec, Masahiro, Takeuchi, Shoji

RSC ADVANCES 4 （ 58 ） 30480 - 30484 2014年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2046-2069

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Three-dimensional neuron-muscle constructs with neuromuscular junctions

Morimoto, Yuya, Kato-Negishi, Midori, Onoe, Hiroaki, Takeuchi, Shoji

BIOMATERIALS 34 （ 37 ） 9413 - 9419 2013年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0142-9612

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Millimeter-Sized Neural Building Blocks for 3D Heterogeneous Neural Network Assembly

Kato-Negishi, Midori, Morimoto, Yuya, Onoe, Hiroaki, Takeuchi, Shoji

ADVANCED HEALTHCARE MATERIALS 2 （ 12 ） 1564 - 1570 2013年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2192-2640

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Metre-long cell-laden microfibres exhibit tissue morphologies and functions

Onoe, Hiroaki, Okitsu, Teru, Itou, Akane, Kato-Negishi, Midori, Gojo, Riho, Kiriya, Daisuke, Sato, Koji, Miura, Shigenori, Iwanaga, Shintaroh, Kuribayashi-Shigetomi, Kaori, Matsunaga, Yukiko T., Shimoyama, Yuto, Takeuchi, Shoji

NATURE MATERIALS 12 （ 6 ） 584 - 590 2013年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1476-1122

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Cellular building unit integrated with microstrand-shaped bacterial cellulose

Hirayama, Kayoko, Okitsu, Teru, Teramae, Hiroki, Kiriya, Daisuke, Onoe, Hiroaki, Takeuchi, Shoji

BIOMATERIALS 34 （ 10 ） 2421 - 2427 2013年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0142-9612

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Cell Origami: Self-Folding of Three-Dimensional Cell-Laden Microstructures Driven by Cell Traction Force

Kuribayashi-Shigetomi, Kaori, Onoe, Hiroaki, Takeuchi, Shoji

PLOS ONE 7 （ 12 ） 2380 - 2385 2012年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1932-6203

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Flexible tactile sensor for shear stress measurement using transferred sub-mu m-thick Si piezoresistive cantilevers

Noda, Kentaro, Onoe, Hiroaki, Iwase, Eiji, Matsumoto, Kiyoshi, Shimoyama, Isao

JOURNAL OF MICROMECHANICS AND MICROENGINEERING 22 （ 11 ） 1553 - 1557 2012年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0960-1317

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Direct Attachment of Microbial Organisms to Material Surfaces Through Sequence-Specific DNA Hybridization

Twite, Amy A., Hsiao, Sonny C., Onoe, Hiroaki, Mathies, Richard A., Francis, Matthew B.

ADVANCED MATERIALS 24 （ 18 ） 2380 - 2385 2012年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0935-9648

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Cellular Microfabrication: Observing Intercellular Interactions Using Lithographically-Defined DNA Capture Sequences

Onoe, Hiroaki, Hsiao, Sonny C., Douglas, Erik S., Gartner, Zev J., Bertozzi, Carolyn R., Francis, Matthew B., Mathies, Richard A.

LANGMUIR 28 （ 21 ） 8120 - 8126 2012年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0743-7463

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Controlled Synthesis of 3D Multi-Compartmental Particles with Centrifuge-Based Microdroplet Formation from a Multi-Barrelled Capillary

Maeda, Kazuki, Onoe, Hiroaki, Takinoue, Masahiro, Takeuchi, Shoji

ADVANCED MATERIALS 24 （ 10 ） 1340 - 1346 2012年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0935-9648

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Microfluidic Control of the Internal Morphology in Nanofiber-Based Macroscopic Cables

Kiriya, Daisuke, Kawano, Ryuji, Onoe, Hiroaki, Takeuchi, Shoji

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 51 （ 32 ） 7942 - 7947 2012年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1433-7851

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Meter-Long and Robust Supramolecular Strands Encapsulated in Hydrogel Jackets

Kiriya, Daisuke, Ikeda, Masato, Onoe, Hiroaki, Takinoue, Masahiro, Komatsu, Harunobu, Shimoyama, Yuto, Hamachi, Itaru, Takeuchi, Shoji

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 51 （ 7 ） 1553 - 1557 2012年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1433-7851

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A neurospheroid network-stamping method for neural transplantation to the brain

Kato-Negishi, Midori, Tsuda, Yukiko, Onoe, Hiroaki, Takeuchi, Shoji

BIOMATERIALS 31 （ 34 ） 8939 - 8945 2010年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0142-9612

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Fusion and Fission Control of Picoliter-Sized Microdroplets for Changing the Solution Concentration of Microreactors

Takinoue, Masahiro, Onoe, Hiroaki, Takeuchi, Shoji

SMALL 6 （ 21 ） 2374 - 2377 2010年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1613-6810

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Parylene-coating in PDMS microfluidic channels prevents the absorption of fluorescent dyes

Sasaki, Hirotaka, Onoe, Hiroaki, Osaki, Toshihisa, Kawano, Ryuji, Takeuchi, Shoji

SENSORS AND ACTUATORS B-CHEMICAL 150 （ 1 ） 478 - 482 2010年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0925-4005

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温度制御転写における自動位置補正技術

岩瀬英治, 尾上 弘晃, 中井亮人, 松本潔, 下山勲

電気学会誌E部門 130 （ 5 ） 188 - 193 2010年

研究論文（学術雑誌）, 共著, 査読有り

Temperature-controlled transfer and self-wiring for multi-color light-emitting diode arrays

Onoe, Hiroaki, Nakai, Akihito, Iwase, Eiji, Matsumoto, Kiyoshi, Shimoyama, Isao

JOURNAL OF MICROMECHANICS AND MICROENGINEERING 19 （ 7 ）  2009年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0960-1317

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Direct Cell Surface Modification with DNA for the Capture of Primary Cells and the Investigation of Myotube Formation on Defined Patterns

Hsiao, Sonny C., Shum, Betty J., Onoe, Hiroaki, Douglas, Erik S., Gartner, Zev J., Mathies, Richard A., Bertozzi, Carolyn R., Francis, Matthew B.

LANGMUIR 25 （ 12 ） 6985 - 6991 2009年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0743-7463

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Probing the mechanical architecture of the vertebrate meiotic spindle

Itabashi, Takeshi, Takagi, Jun, Shimamoto, Yuta, Onoe, Hiroaki, Kuwana, Kenta, Shimoyama, Isao, Gaetz, Jedidiah, Kapoor, Tarun M., Ishiwata, Shin'ichi

NATURE METHODS 6 （ 2 ） 167 - 172 2009年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1548-7091

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DNA-barcode directed capture and electrochemical metabolic analysis of single mammalian cells on a microelectrode array

Douglas, Erik S., Hsiao, Sonny C., Onoe, Hiroaki, Bertozzi, Carolyn R., Francis, Matthew B., Mathies, Richard A.

LAB ON A CHIP 9 （ 14 ） 2010 - 2015 2009年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1473-0197

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Microfabricated mobile microplates for handling single adherent cells

Onoe, Hiroaki, Takeuchi, Shoji

JOURNAL OF MICROMECHANICS AND MICROENGINEERING 18 （ 9 ） 9413 - 9419 2008年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0960-1317

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Three-dimensional integration of heterogeneous silicon micro-structures by liftoff and stamping transfer

Onoe, Hiroaki, Iwase, Eiji, Matsumoto, Kiyoshi, Shimoyama, Isao

JOURNAL OF MICROMECHANICS AND MICROENGINEERING 17 （ 9 ） 1818 - 1827 2007年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0960-1317

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Three-dimensional sequential self-assembly of microscale objects

Onoe, Hiroaki, Matsumoto, Kiyoshi, Shimoyama, Isao

SMALL 3 （ 8 ） 1383 - 1389 2007年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1613-6810

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Direct measurement of the binding force between microfabricated particles and a planar surface in aqueous solution by force-sensing piezoresistive cantilevers

Onoe, H, Gel, M, Hoshino, K, Matsumoto, K, Shimoyama, I

LANGMUIR 21 （ 24 ） 11251 - 11261 2005年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0743-7463

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Three-dimensional micro-self-assembly using hydrophobic interaction controlled by self-assembled monolayers

Onoe, H, Matsumoto, K, Shimoyama, I

JOURNAL OF MICROELECTROMECHANICAL SYSTEMS 13 （ 4 ） 603 - 611 2004年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1057-7157

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