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RESEARCH PROJECTS

OVERVIEW

Based on micro- and nano-scale fabrication technologies, our group is exploring engineering principles to create integrative systems and devices using various materials including molecules, colloids, polymers, living cells and tissues.

Current working projects are:

  • hydrogel microstructures for soft robotics, cellular scaffolds and medical applications
  • biologically-inspired static/dynamic self-assembly systems
  • integrated devices using multiscale elements
  • MEMS/NEMS/microfluidics

Hydrogel microstructures

Hydrogels are water-containing polymer networks and have been studied for food products, environment-friendly materials, helthcare and medical applications. Recent advances of microfabrication technologies enable the microfabrication of soft materials including hydrogels and plastic polymers, which are expected to emerge novel functions and applications. Our group has developed methods for the microfabrication of hydrogels and has explored their applications in the fields of materials science, soft robotics, biotechnology and medical treatment.

 

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-programmed self-assembly

In this half century, sientists found DNA playing a central role in coding, replicating and transcripting genetic information in life system. As well as advances in the biological sence, DNA molecule itself has resently been used as functional nanoscale building blocks to engineer nanoscale structures, molecular calculation and computing, chemical sensing and structure conformation (actuation), recognized as DNA Nanotechnology. Our group has focused on the use of DNA molecules as a programmable linker between molecular objects and micro-scale objects, and has studied on constructing macroscopic structures and systems controlled by molecular events.

 

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]

Biologically-inspired dynamic/static self-assembly system

Understanding of dynamic and complex self-assembly and self-organization phenomena, which are frequently seen in nature (especially in life system), is one of the centerpiece of science in the past century. These systems are usually hierarchical and dynamic in the range from molecular interactions (nanometer-scale) to micro-to-millimeter structures, and require a non-equilibrium open system for both materials and energy. Aattempts to artificially reconstruct such self-assembly or self-organization systems have recently been focused as one of the ultimate goals for both scientists and engineers. Our group has explored to understand these complex and diverse mechanisms of self-assembly and self-organization, and has challenged the artificial reconstruction of those systems both from the standpoints of science and engineering.

 

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]

Integrated microsystems for bridging multiscale elements

Integration of multiscale elements from molecular scale to macroscopic device scale is a key technological issue to develop industrial products employing unpresent smart functions for improving our life style. Microscale technology such as MEMS/NEMS is a powerful tool to achieve the multiscal integration. Our group has developed integrated microsystems using heterogeneous materials and elements ranging varisou scales.

 

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/Microfluidics/Micro-Nanoscale physics

Top-down machining processing at micro- and nano-scale have been deepned with various state-of-art technologies. Among these technologies, the MEMS (Micro-Electro-Mechancal Systems) technology based on photolithograpy and semiconductor processing has improved the accuracy of the fabrication and has expand their target materials for this decades. Our group has developed MEMS/NEMS/microfluidic systems that could combine multiscale elements from molecular to device scales and has also focuesd on device phyisics through the fabrication.