Published papers

© 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.

© 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.

© 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.

© 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.

© 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.

© 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.

© 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.

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.

© 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.

© 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.

© 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.

© 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.

© 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.

© 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.

© 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.

© 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.

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.

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.

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.

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.