Japanese
English我々の研究室では，マイクロナノスケールの微細加工技術（マイクロマシン・MEMS/NEMS）を基盤技術として，機能性分子素子，ハイドロゲルなどの高分子材料，また細胞や組織に代表される生体材料など，様々なスケールの素材を幅広く統合する物作りの構築法や，それにより創り出される新たなシステムを研究を行っています．
具体的には主に以下のトピックにて研究を実施しています．
- 生物規範型マイクロソフトロボティクス
- 工学的アプローチによる生体組織構築と再生医療への応用
- 動的・静的な自己組織化現象の再構築とその工学応用
- 機能性材料統合による生体・環境情報のセンシングデバイス
- DNAによりプログラムされたマイクロシステム
- 機能性ハイドロゲルマイクロビーズ形成技術とドラッグデリバリー（DDS）応用
- マイクロ流体システム/マイクロ・ナノスケールの物理
ここに挙げた研究テーマ以外にも，ディスカッションにより日々新しいテーマ・トピックが生まれています．我々は研究室での研究教育活動を通じて，深い専門性と幅広い視点を持つ人材を育成すると同時に，人々にインスピレーションを与え再利用されるアイディア・考え方を発信してきたいと考えています．
自分のアイディアを試してみたい，研究成果を海外で発表してみたい，世界を驚かせる研究をしたい．．．我々のグループでぜひ一緒に研究をしましょう！
"In nature, most microorganisms have motility, which is essential for their survival or reproduction. To move, some microorganisms have evolved soft spiral-shaped flagella, which rotate through specialized motors. Many of these microorganisms can change the morphology of their spiral-shaped flagella to control their motility. Herein, by mimicking these flagella, spiral-shaped microswimmers are developed for various applications, such as target drug delivery, micro-object transport, and micro-fluid manipulation. In previous studies, numerous fabrication methods of spiral-shaped microswimmers are developed. However, the swimming direction and velocity are controlled only by external systems, such as magnetic fields, because the spiral body is not able to deform. Therefore, this soft spiral-shaped microswimmer for autonomous swimming control by detecting surrounding stimuli is proposed. The velocity of microswimmer largely depends on the geometry of the microswimmer’s body. Through usage of a stimuli-responsive hydrogel in the microswimmer, the geometry autonomously changes in response to the surrounding stimuli. Using finite-element simulation, it is revealed that the pattern angle is an important parameter for acceleration/deceleration of the microswimmer. The dimensionless velocity of the fabricated bilayered spiral swimmer changes by deforming the geometry in response to the surrounding thermal stimuli." 
"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." 
"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." 
"Animal pathology models play an important role in elucidating pathology, evaluating drug efficacy, and studying therapeutics. This paper presents the creation of a 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." 
"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 reactions and achieves contraction both at the tissue and cell levels. 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 research and pharmacokinetic testing." 
"We present an extracellular matrix (ECM)-based stretchable microfluidic system for culturing in vitro threedimensional
(3D) vascular tissues, which mimics in vivo blood 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." 
"Crypt-like structures are indispensable to fabricating an artificial intestinal tissue reproducing the arrangement of cell types in vivo. This paper presents the 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." 
"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." 
"This paper describes a system through which the self-assembly of anisotropic hydrogel microparticles is achieved, which also enables dynamic transformation of the assembled structures. Using a centrifuge-based microfluidic device, anisotropic hydrogel microparticles encapsulating superparamagnetic materials on one side are fabricated, which respond to a magnetic field. We successfully achieve dynamic assembly using these hydrogel microparticles and realize three different self-assembled structures (single and double pearl chain structures, and close-packed structures), which can be transformed to other structures dynamically via tuning of the precessional magnetic field. We believe that the developed system has potential application as an effective platform for a dynamic cell manipulation and cultivation system, in biomimetic autonomous microrobot organization, and that it can facilitate further understanding of the self-organization and complex systems observed in nature." 
"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
." 
"Synthetic DNA strands can be attached to the plasma membrane of living cells to equip them with artificial adhesion “receptors” that bind to complementary strands extending from material surfaces. This approach is compatible with a wide range of cell types, offers excellent capture efficiency, and can potentially be used to create complex multicellular arrangements through the use of multiple capture sequences.The utility of this approach is demonstrated through the observation of patterned cells as they communicate by diffusion-based paracrine signaling." 
"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 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.." 
"This paper reports a unique phase separation behavior, a simultaneous-crosslinking-driven phase sep- aration 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 de- livery 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." 
"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 proteinswas 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." 
"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 conditions. 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.." 
