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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
  • DNAによりプログラムされた自己組織化
  • 動的・静的な自己組織化現象の再構築とその工学応用
  • マルチスケール・異種材料を繋ぐデバイス統合技術
  • MEMS/NEMS/マイクロ流体デバイス

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,医療品・食料品・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,その機能を活かすことでの材料科学・ソフトロボティクス・生命科学・医療への応用展開を行っています.

 

Centrifuge-based multi-compartmental hydrogel microparticles

We report a one-step synthetic method that provides sphere-based microparticles possessing multiple compartments with a controlled 3D morphology in a monodisperse fashion. The particle sizes varied, and their shapes could be tuned to ellipses or fibers. Our method uses liquid-air droplet formation from laminar flows of sodium alginate solution at the orifice of a multi-barrelled capillary and immediate gelation in CaCl2 solution under ultrahigh gravity generated by centrifugation. Other than biphasic-Janus particles, varying the capillary design makes it possible to generate particles possessing three-, four-, and six-compartment body compositions with designed geometries. As confirmed by the encapsulation of magnetic colloids and cells with 91% viability inside Janus particles and the magnetic self-assembly of those particles into a pearl-chain structure, the compartmentalized particles have the ability to encapsulate unprecedented combinations of materials, from colloids to cells. [Ref] Maeda et al., Advanced Materials, 2012. [link]

 

Microfluidic tehcnology for fabricating functional hydrogel microfibers

Fiber-shaped materials are widely used as a basic building blocks in various scale from molecular level to architectures. Fiber's flexibility enables various applications such as folded materials, flexible structures, and enhanced strength. We have pursued to create a platform of functional materials and the construction methodoly. We have developed a microfluidic device to create various types of hydrogel microfiber based on a calcium alginate and have advacned the functionality of the hydrogel microfibers. Espceially, self-folded and self-assembly approach using fiber-shaped functional materials will give a unique and effective pahtway toward 3D heterogenous strucutres and systems such as external field-triggered actuators and sensors.

 

Cell-laden hydrogel microfibers for 3D tissue construction and medical implantation

Artificial reconstruction of fibre-shaped cellular constructs could greatly contribute to tissue assembly in vitro. Here we show that, by using a microfluidic device with double-coaxial laminar flow, metre-long core–shell hydrogel microfibres encapsulating ECM proteins and differentiated cells or somatic stem cells can be fabricated, and that the microfibres reconstitute intrinsic morphologies and functions of living tissues. We also show that these functional fibres can be assembled, by weaving and reeling, into macroscopic cellular structures with various spatial patterns. Moreover, fibres encapsulating primary pancreatic islet cells and transplanted through a microcatheter into the subrenal capsular space of diabetic mice normalized blood glucose concentrations for about two weeks. These microfibres may find use as templates for the reconstruction of fibre-shaped functional tissues that mimic muscle fibres, blood vessels or nerve networks in vivo. [Ref] Onoe et al., Nature Materials, 2013. [link]


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]

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。

 

Sequential self-assembly of microscale objects by controlling pH

We describe sequential 3D self-assembly of microfabricated silicon parts (~10 µm) in an aqueous solution. We employed hydrophobic interaction, a repulsive doublelayer force, and the van der Waals (VDW) force, which are dominant in the aggregation or dispersion of colloid particles, as the interactive forces between the microfabricated parts. Our concept of sequential self-assembly consists of two assembly steps: Microfabricated silicon parts, which have two different binding sites, are stirred in an aqueous solution and then self-assemble through interactions between the parts. The self-assembly sequence is controlled by simply changing the pH of the aqueous solution. We believe that this self-assembly control mechanism can be widely applied to combining microfabricated objects with colloidal particles or biological molecules; this would pave the way towards self-assembled heterogeneous 3D systems. [Ref] Onoe et al., Small, 2007. [link]

 

Magnetically-driven self-assembly of hydrogel Janus microparticles

To examine the functionality that our Ca-alginate hydrogel Janus particles acquire when used to encapsulate different materials, we magnetized one hemisphere of the Janus particles by encapsulating magnetic nanocolloids and applying an external magnetic field. The magnetic Janus particles self-assembled into pearl-chain structures under the static external magnetic field. Furthermore, to examine the biocompatibility of our method, we encapsulated viable cells in the other hemisphere of the magnetized particles. Cells were successfully co-encapsulated with the magnetic nanobeads, and the viability of the encapsulated cells was 91%. We are now trying to apply rotating/alternating/precessional magnetic field to our magnetized micro particles for dynamic self-assembly. [Ref] Maeda et al., Advanced Materials, 2012. [link]

マルチスケール・異種材料を繋ぐデバイス統合技術

機能性材料の研究は目覚ましく、日々新たな素材が産まれています。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、統合する技術、様々なスケール・種類の材料や要素を統合し、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。

 

Heterogeneous electric materials on flexible substrate

flexible substrate for multi-color inorganic LED displays. The LED bare chips (240 μm × 240 μm × 75 μm), which were diced on an adhesive sheet by the manufacturer, were transferred to a flexible polyimide substrate by our temperature-controlled transfer (TCT) and self-wiring (SW) processes. In these processes, low-melting point solder (LMPS) and poly-(ethylene glycol) (PEG) worked as adhesive layers for the LED chips during the TCT processes, and the adhesion force of the LMPS and PEG layers was controlled by changing the temperature to melt and solidify the layers. After the TCT processes, electrical connection between the transferred LED chips and the flexible substrate was automatically established via the SW process, by using the surface tension of the melted LMPS. This TCT/SW method enabled us to (i) handle arrays of commercially available bare chips, (ii) arrange multiple types of chips on the circuit substrate by simply repeating the TCT processes and (iii) establish electrical connection between the chips and the substrate automatically. Applying this transfer printing and wiring method, we experimentally demonstrated a 5-by-5 flexible LED array and a two-color (blue and green) LED array. [Ref] Onoe et al., Journal of Micromechanics and Microengineering, 2009. [link]

 

Microfabricated sensors Integrated on flexible sheet

We propose a flexible tactile sensor using sub-μm-thick Si piezoresistive cantilevers for shear stress detection. The thin Si piezoresistive cantilevers were fabricated on the device layer of a silicon on insulator (SOI) wafer. By using an adhesion-based transfer method, only these thin and fragile cantilevers were transferred from the rigid handling layer of the SOI wafer to the polydimethylsiloxane layer without damage. Because the thin Si cantilevers have high durability of bending, the proposed sensor can be attached to a thin rod-type structure serving as the finger of a robotic hand. The cantilevers were arrayed in orthogonal directions to measure the X and Y directional components of applied shear stresses independently. [Ref] Noda et al., Journal of Micromechanics and Microengineering, 2012. [link]

MEMS/NEMS/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。