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研究プロジェクト

概要

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.

  • ハイドロゲルによるマイクロ構造体
  • 工学的アプローチによる生体組織構築
  • 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情報デバイス
  • マイクロ流体デバイス/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!

 

 

ハイドロゲルによるマイクロ構造体

ハイドロゲルは水を含む高分子ネットワークで出来ており,生体や環境に優しい材料として注目されています.近年のマイクロ加工技術の進歩により,金属や半導体のみならず,ポリマーやハイドロゲルなどのソフトマテリアルもマイクロスケールでの精密加工ができるようになってきました.これにより,ハイドロゲル材料の新たな機能や応用可能性を引き出すことが期待できます.本研究室では,ハイドロゲルのマイクロ加工及びマイクロ構造構築に関する方法論の構築と,その機能を活かしたソフトアクチュエータやドラックデリバリーシステム(DDS)等への応用展開を行っています.

 

Spring-shaped stimuli-responsive hydrogel actuator with large deformation

"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." [Ref] Yoshida et.al., Sensors and Actuators B: Chemical, 2018. [link]

 

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

"Stimuli-responsive microfibers are fabricated by extruding mixed solutions of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) and sodium alginate (Na-alginate) using a microfluidic spinning system. The fabricated microfibers shrink and swell with temperature and/or pH. By controlling the extruded laminar flow, microfibers capable of anisotropic shrinkage are fabricated. Cross-sectional microscale geometries of microfibers, including double layering and hollowness, are successfully controlled by patterning the laminar flow during microfiber formation, resulting in hydrogels capable of folding/unfolding motions and fluid pumping. In addition, macroscopic 3D-bundle structures are assembled with these microfibers. We believe that our microfibers can be applied to various applications such as soft actuators, soft robots, and micropumps." [Ref] Nakajima, et.al., Soft Matter, 2017. [link]

 

 

工学的アプローチによる生体組織構築

我々の身体は様々な器官,組織によって構成されています.それら生体内の器官や組織の構造を細胞レベルでみると,多種多様な細胞が方向性を持って三次元的に配列した構造をしていることが知られています.この生体内(in vivo)の構造を人工的に生体外(in vitro)で模擬することができれば,生体の持つ器官や組織の機能を我々の手で再構築可能であると考えられます.本研究室では,細胞を工学的視点で材料として捉え,それらを秩序立った三次元組織として形成するボトムアップ的構成法の確立と,その組織による生理機能の発現を目指します.この技術により,再生医療や病理解明のための人工組織モデルの創出,および新薬開発のためのツールとして応用を目指して研究を展開しています.

 

Fiber-shaped artificial tissue with microvascular networks for bottom-up tissue reconstruction

"This paper describes a fiber-shaped microscale tissue with blood vessel networks. We co-cultured Hep-G2(Human hepatic epithelial cell line) and HUVEC(human umbilical endothelial cell) in a collagen/alginate core-shell hydrogel microfiber fabricated by using a microfluidic device. By culturing these microfibers, we found that blood vessel networks were constructed in the hepatic tissue. In addition, by arranging the fiber-shaped tissues to construct macroscale tissue assembly, we confirmed the connection of blood vessel networks between the assembled fiber-shaped tissues. We believe that our fiber-shaped tissue with blood vessel networks could contribute to the long-term maintenance of macroscale tissues in the tissue engineering field." [Ref] Sato et al., MEMS 2017, 2017.

 

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

"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." [Ref] Matsushiro, et.al., Biotechnology and Bioengineering, 2018. [link]

 

Double-layer collagen microtube for perfusable heterogeneous culture

"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." [Ref] Itai, et.al., MicroTAS 2017, 2017.

 

 

動的・静的な自己組織化現象の再構築とその工学応用

自然界、特に生命現象などに顕著にみられる動的で複雑な自己組織化現象の理解は、科学における中心的なトピックの一つです。このような現象は、エネルギーの流入・流出により維持される動的な現象であり、また分子スケールからマクロな世界まで階層的に相互作用し合う、非線形なシステムであると解釈されています。このようなシステムを人工的に再構成する(創りだす)ことは、科学者にとっても工学者にとっても究極の目標の一つだと言えます。本研究室では、マイクロスケールの加工技術をベースにして、このような動的な自己組織化システムの実験的な構築を目指すと同時に、工学的な応用展開の探索を行います。

 

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

"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." [Ref] Yoshida et al., Journal of Applied Physics, 2016. [link]

 

 

機能性材料統合による情報デバイス

機能性材料の研究は目覚ましく、日々新たな素材が生まれています.これらの素材を統合し、我々が日常利用可能なデバイスを作るためには、マイクロスケールでの加工技術やMEMS(Micro-Electro-Mechanical Systems)が威力を発揮すると我々は考えています.本研究室では、コロイド結晶やナノカーボン材料,機能性高分子としてのDNAなどを統合し,一つのシステムとして機能する方法論の開発を通して新しいデバイスの提案を行います.

 

Graphene-based inline pressure sensor integrated with microfluidic elastic tube

"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." [Ref] Inoue et al., Journal of Micromechanics and Microengineering, 2018. [link]

 

Multiple structural color hydrogel array integrated with microfluidic chip for biochemical sensor

"This paper describes multiple structural color hydrogel array integrated with a two-layered microfluidic chip. The microfluidic chip can sense multiple physical/chemical targets (ex. concentration of chemicals and temperature) at the same time simply by eye-visible color changes of the arrayed stimuli-responsive structural color hydrogels in the top chambers. Sample solution was introduced in the bottom channel and react to the arrayed hydrogel via sandwiched porous membrane. We evaluated our device by measuring ethanol/water concentration and temperature, and confirmed the visible color changes of our sensor without any external equipment. We believe that our sensing device could be applied to a biochemical sensor or microanalytical chip for environmental monitoring sensor and wearable healthcare devices." [Ref] Niibe et al., Transducers 2017, 2017.

 

 

DNAによりプログラムされた自己組織化

DNAは生命の遺伝情報の本質であり、その分子構造の決定により生命科学が劇的に進歩してきました。また同時に、DNAの分子自体を機能的なナノスケールの分子部品として工学的に利用する「DNAナノテクノロジー」という分野が生まれ、分子演算やコンピューティング、化学物質のセンシング、ナノスケールのパターンや3次元構造を構築などの研究が盛んになっています。本研究室では、DNA分子をナノとマイクロのスケールを繋ぐ「プログラム可能なリンカー」として利用し、分子の世界とマクロな世界が互いに相互作用するシステムの研究を行います。

 

DNA-programmed micropatterning of living cells

"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." [Ref] Onoe et al., Langmuir, 2012. [link]

 

 

マイクロ流体デバイス/マイクロ・ナノスケールの物理

マイクロナノスケールにおけるトップダウンの機械加工技術は様々に深化してきました.その中で,フォトリソグラフィーによる半導体加工技術から機械要素を構築するマイクロマシン・MEMS技術(Micromachine, Micro-Electro-Mechanical-Systems)は、最初はシリコンの加工から始まりましたがここ十年で精度と対象とする材料が広がり,分子スケールからデバイス技術をつなぐための中核的な技術になりつつあります.本研究室では,これらのためのMEMS/NEMS/マイクロ流体デバイスの研究を行います.特に他のスケールの材料やシステムとの相互関係を意識して研究を展開すると共に,その過程でおこる諸処の物理現象にも興味をもって取組みます.

 

Liquid-filled flexible micro suction-controller array for enhanced robotic object manipulation

"With the intent to enhance robotic manipulation, this paper describes a novel liquid-filled flexible micro suction-controller array (MISCA) for humanoid robotic hands that can hold curved or grooved surface objects. The proposed MISCA comprises 49 suction units arrayed in a 10 mm × 10 mm area of flexible polydimethylsiloxane sheet. Each 1 mm diameter suction unit generates suction force independently. An incompressible working fluid (ethylene glycol) is injected or drained through microchannels in the MISCA using a syringe pump to control the suction force. In experiments, the proposed MISCA effectively generated suction forces of 0.96-1.54 N on flat surfaces, 0.43-0.63 N on cylindrical surfaces, and 0.60-0.83 N on spherical surfaces. In addition, the proposed MISCA was demonstrated to successfully manipulate a 75 g flat object (a watch), a 1-g grooved object (a yen coin), and a curved object (a tablet) using suction control." [Ref] Nishita et al., Journal of Microelectromechanical Systems, 2017. [link]

 

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

"We herein report the micropatterning of flexible multiple photonic colloidal crystal gels (PCCGs) using single-layered microchannels. These patterned PCCGs exhibit structural colors that can be tuned by adjustment of the diameter and concentration of the colloidal particles in precursor solutions of N-isopropylacrylamide (NIPAM) or polyethylene glycol diacrylate (PEGDA). The precursor solutions containing dispersed colloidal particles were selectively injected into single-layered microchannels where they polymerized rapidly. The shape, density, and height of the patterned PCCG pixels were determined by the microchannels, which in turn determined the optical properties of the PCCG arrays. Furthermore, the preparation of three different types of PCCGs exhibiting three different structural colors at a high pixel density was demonstrated successfully using the single-layered polydimethylsiloxane (PDMS) microchannels. Finally, the optical reflective properties and the mechanical flexibility of the patterned multiple PCCG arrays were evaluated. We expect that our method for the preparation of such patterned PCCG arrays will contribute to the development of flexible optical devices." [Ref] Suzuki et al., Langmuir, 2017. [link]

 

Microfluidic-based flexible reflective multicolor display

"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." [Ref] Kobayashi et al., Microsystems & Nanoengineeringvolume, 2018. [link]