Fumihito Arai

Nagoya University, Nagoya, Aichi, Japan

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Publications (846)322.09 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Trans-catheter endovascular stent grafting minimizes trauma and increases the benefitting patient population. However, the alignment between stent graft branches and vasculature branches remains time-consuming and challenging, and such techniques require a significant amount of contrast agent for imaging. Methods: A new framework for intravascular reconstruction based on sensor fusion between intravascular ultrasound (IVUS) imaging and electromagnetic (EM) tracking was proposed. A new image processing method was presented to realize fully automatic processing of IVUS imaging and 3D reconstruction in real time, as well as branch detection for alignment and deployment. Complementary navigation using CT data allows for efficient catheter advancement and assistant clinical judgement. Results: The reconstruction of an in vitro descending aorta phantom with branches was realized at 35 Hz, with cross-section radius average error of 0.64 mm. Conclusion: The proposed method demonstrates significant potential for clinical applications, enables navigation for precise alignment and placement for stent grafting to reduce surgical time, and decreases hemorrhagic collisions and the use of contrast agent. Copyright © 2016 John Wiley & Sons, Ltd.
    No preview · Article · Feb 2016 · International Journal of Medical Robotics and Computer Assisted Surgery
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    ABSTRACT: This paper presents a novel hybrid medical stent device. This hybrid stent device formed by fractal mesh structures provides a flow-diverting effect and stent-assisted coil embolization. Flow-diverter stents decrease blood flow into an aneurysm to prevent its rupture. In general, the mesh size of a flow-diverter stent needs to be small enough to prevent blood flow into the aneurysm. Conventional flow-diverter stents are not available for stent-assisted coil embolization, which is an effective method for aneurysm occlusion, because the mesh size is too small to insert a micro-catheter for coil embolization. The proposed hybrid stent device is capable of stent-assisted coil embolization while simultaneously providing a flow-diverting effect. The fractal stent device is composed of mesh structures with fine and rough mesh areas. The rough mesh area can be used to insert a micro-catheter for stent-assisted coil embolization. Flow-diverting effects of two fractal stent designs were composed to three commercially available stent designs. Flow-diverting effects were analyzed using computational fluid dynamics (CFD) analysis and particle image velocimetry (PIV) experiment. Based on the CFD and PIV results, the fractal stent devices reduce the flow velocity inside an aneurism just as much as the commercially available flow-diverting stents while allowing stent-assisted coil embolization.
    No preview · Article · Oct 2015 · Medical & Biological Engineering
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    ABSTRACT: An unexpected phenomenon of red blood cell bouncing back and forth between the walls inside a microfluidic channel was observed during experiments, and is presented as ``Cell Pinball" in this paper. In general, cells in a microfluidic environment are supposed to move along the streamlines parallel to channel walls when the Reynolds number is small, and the inertia of the cells becomes negligible. However, the cell pinball presented in this paper does not only move along the stream lines but also move across the channel with velocity component perpendicular to the stream lines while the Reynolds number is only 0.74. Furthermore, the motion in the direction perpendicular to the stream lines reverses when the cell pinball hits a wall as it ``bounces" at the wall. The phenomenon caught our attention, and is investigated with both microbead visualization and confocal microscope. Consistent patterns of rotation with respect to the directions of motion are observed. A kinematic model is proposed to interpret the phenomenon, and it is believed that the phenomenon is caused by the separation of the centroid of cell and the contact point. The model successfully interprets the features of cell pinball, and the estimated separation between the centroid and the contact point are presented.
    No preview · Article · Jul 2015 · Lab on a Chip
  • Y. Murozaki · S. Sakuma · F. Arai
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    ABSTRACT: We present a super wide-measurement range load sensor with high-durability for multi-biosignal sensing in daily life. We employed quartz crystal resonator (QCR) load sensor with super wide range (from 6 × 10-5 to 30 [N]) for sensing of biosignals ranging from mN order (e.g. heartbeat) to 100 N order (e.g. body motion). Furthermore, we implemented an outer case which makes the sensor durable against unexpected loads in practical use. The outer case increased the durability of the sensor 88 times higher than the sensor without outer case. Finally we succeeded in simultaneous sensing of heartbeat (≈ 100 [mN]) and body motion (≈ 25 [N]) with identical sensor.
    No preview · Article · Jun 2015 · Proceedings - IEEE International Conference on Robotics and Automation
  • H. Sugiura · S. Sakuma · M. Kaneko · F. Arai
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    ABSTRACT: This paper proposes the method for mechanical characterization of floating cells on a microfluidic chip. We measured the reactive force of cells on the chip by applying mechanical deformation to the cells. Particularly we focused on the method to improve the sensing resolution of the probe position by using the phase detection of moiré fringe. This method realized approximately ten times higher resolution compared to the previous method. The detailed data suggest some unique characteristics of cells. We discussed the phenomenon seen on the data with a mechanical model, which is based on Heltzian contact theory in the light of stiff nucleus.
    No preview · Article · Jun 2015 · Proceedings - IEEE International Conference on Robotics and Automation
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    ABSTRACT: We propose a method to characterize the mechanical properties of cells using a robot-integrated microfluidic chip (robochip) and microscopy. The microfluidic chip is designed to apply the specified deformations to a single detached cell using an on-chip actuator probe. The reaction force is simultaneously measured using an on-chip force sensor composed of a hollow folded beam and probe structure. In order to measure the cellular characteristics in further detail, a sub-pixel level of resolution of probe position is required. Therefore, we utilize the phase detection of moiré fringe. Using this method, the experimental resolution of the probe position reaches 42 nm. This is approximately ten times smaller than the optical wavelength, which is the limit of sharp imaging with a microscope. Calibration of the force sensor is also important in accurately measuring cellular reaction forces. We calibrated the spring constant from the frequency response, by the proposed sensing method of the probe position. As a representative of mechanical characteristics, we measured the elastic modulus of Madin-Darby Cannie Kidney (MDCK) cells. In spite of the rigid spring constant, the resolution and sensitivity were twice that achieved in our previous study. Unique cellular characteristics can be elucidated by the improvements in sensing resolution and accuracy.
    No preview · Article · Jun 2015 · Micromachines
  • Source
    Takeshi Hayakawa · Shinya Sakuma · Fumihito Arai
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    ABSTRACT: We propose a novel on-chip 3D cell rotation method based on a vibration-induced flow. When circular vibration is applied to a microchip with micropillar patterns, a highly localized whirling flow is induced around the micropillars. The direction and velocity of this flow can be controlled by changing the direction and amplitude of the applied vibration. Furthermore, this flow can be induced on an open chip structure. In this study, we adopted a microchip with three micropillars arranged in a triangular configuration and an xyz piezoelectric actuator to apply the circular vibration. At the centre of the micropillars, the interference of the vibration-induced flows originating from the individual micropillars induces rotational flow. Consequently, a biological cell placed at this centre rotates under the influence of the flow. Under three-plane circular vibrations in the xy, xz or yz plane, the cell can rotate in both the focal and vertical planes of the microscope. Applying this 3D cell rotation method, we measured the rotational speeds of mouse oocytes in the focal and vertical planes as 63.7 ± 4.0° s−1 and 3.5 ± 2.1° s−1, respectively. Furthermore, we demonstrated the transportation and rotation of the mouse oocytes and re-positioned their nuclei into a position observable by microscope.
    Preview · Article · May 2015
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    ABSTRACT: We propose a system that transports oocytes and measures their mechanical characteristics in an open environment using a robot integrated microfluidic chip (chip). The cells are transported through a micropillar array in the chip, and their characteristics are measured by a mechanical probe and a force sensor. Because the chip has an open microchannel, important cells such as oocytes are easily introduced and collected without the risk for losing them. In addition, any bubbles trapped in the chip, which degrade the measurement precision, are easily removed. To transport the oocytes through the open microchannel, we adopt a transportation technique based on a vibration-induced flow. Under this flow, oocytes arrive at the measurement point, where their mechanical characteristics are determined. We demonstrate the introduction, transportation, measurement of mechanical characteristics, and collection of oocytes using this system.
    No preview · Article · May 2015 · Micromachines
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    ABSTRACT: In this paper, we propose the selective adhesion and rapid injection of a fluorescent sensor into a target cell via the optical control of zeta potential and local vibration stimulus using optical tweezers. A multi-fluorescent sensor, which can respond to both temperature and pH, was encapsulated in anionic lipid layers containing a photochromic material (spiropyran) via the layer-by-layer method. The zeta potential of the lipid layers containing spiropyran was adjusted from negative to positive by photo-isomerization of spiropyran using UV illumination. A single sensor was manipulated by optical tweezers and transferred to a cell surface, thereafter adhering selectively to the cell surface under UV illumination without excess sensor adhesion. We then drove the focal point of the optical tweezers to move up and down circularly near the sensor, mimicking a vibration on the sensor or rapid injection. The surface zeta potential of the liposome layers was measured using a zeta potential analyzer. The fluorescence resonance energy transfer (FRET) method was used to observe the changes in contact area between the adhered sensor and cell membrane before and after vibration. Holographic optical tweezers (HOT) and laser confocal microscopy were used to manipulate the single sensor and to capture fluorescent images. The results showed that the vibration applied on the sensor could push down the sensor, inducing a downward displacement. This displacement caused a corresponding deformation of the cell membrane, which increased the contact area between the sensor and the cell membrane. Without vibration, the sensor was injected into the cytoplasm in 5 h at an injection rate of 40%. By applying the vibration stimulus, we succeeded in the rapid injection of the sensor in 30 min at an injection rate of 80%.
    No preview · Article · May 2015 · Sensors and Actuators B Chemical
  • Source
    Wenjing Huang · Fumihito Arai · Tomohiro Kawahara
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    ABSTRACT: An eggshell is a porous microstructure that regulates the passage of gases to allow respiration. The chick embryo and its circulatory system enclosed by the eggshell has become an important model for biomedical research such as the control of angiogenesis, cancer therapy, and drug delivery test, because the use of embryo is ethically acceptable and it is inexpensive and small. However, chick embryo and extra-embryonic blood vessels cannot be accessed freely and has poor observability because the eggshell is tough and cannot be seen through, which limits its application. In this study, a novel artificial eggshell with functionalized surface is proposed, which allows the total amount of oxygen to pass into the egg for the chick embryo culturing and has high observability and accessibility for embryo manipulation. First, a 40-mm enclosed cubic-shaped eggshell consisting of a membrane structure and a rigid frame structure is designed, and then the threshold of the membrane thickness suitable for the embryo survival is figured out according to the oxygen-permeability of the membrane structure. The designed artificial eggshell was actually fabricated by using polydimethylsiloxane (PDMS) and polycarbonate (PC) in the current study. Using the fabricated eggshell, chick embryo and extra-embryonic blood vessels can be observed from multiple directions. To test the effectiveness of the design, the cubic eggshells were used to culture chick embryos and survivability was confirmed when PDMS membranes with adequate oxygen permeability were used. Since the surface of the eggshell is transparent, chick embryo tissue development could be observed during the culture period. Additionally, the chick embryo tissues could be accessed and manipulated from outside the cubic eggshell, by using mechanical tools without breakage of the eggshell. The proposed "Egg-in-Cube" with functionalized surface has great potential to serve as a promising platform for biomedical research.
    Full-text · Article · Mar 2015 · PLoS ONE
  • C.-H.D. Tsai · Makoto Kaneko · Fumihito Arai
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    ABSTRACT: A method for evaluating red blood cell (RBC) deformability by different channel width in a microfluidic device is proposed. While conventional methods usually have only one test channel to deform RBCs for the evaluation, a design including three test channels with different width is utilized in this work. The proposed design have the advantage of generating a wider range of deformation to each RBC, thus the RBC deformability can be appropriately determined. Experiments on normal RBCs are conducted, and RBC motion through the channels is recorded and analyzed. The velocity drop, the velocity difference between a RBC and flowing fluid, is utilized as an index for the RBC response during deformation. According to the analysis, the relation between the velocity drop and amount of deformation of the RBCs is found nicely fitted with a modified contact model with R2 = 0.91, and the RBC deformability is successfully evaluated as in two deformability constants Cd and ζ.
    No preview · Article · Mar 2015
  • T. Monzawa · S. Sakuma · F. Arai · M. Kaneko
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    ABSTRACT: This paper reports the on-chip Fluid Separated Volumetric Flow Converter (FSVFC) capable of high speed cell position control with high resolution. There are various situations where we need to avoid mixing working fluid and actuation fluid for biological considerations, and such demand motivates the development of FSVFC. The proposed on-chip comb shaped FSVFC is composed of two separated groups of microfluidic channels arranged in parallel, and the main advantage is that actuation can be transmitted through the FSVFC without fluids being mixed. We succeeded in manipulating the position of a cell in microfluidic channel in the working area with the FSVFC as well as an online high speed vision sensor and a high speed PZT actuator. According to the experimental results, the average rise time of 12 miliseconds and the position control within 240 nanometers are achieved.
    No preview · Article · Feb 2015 · Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)
  • R. Murakami · M. Kaneko · S. Sakuma · F. Arai
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    ABSTRACT: During the deformability test of Red Blood Cell (RBC) by utilizing a micro fluidic channel, we found an interesting phenomenon where some RBCs behave just like elastic pinball with the motion in the perpendicular direction with respect to the main flow line, while most of RBCs simply move along the main flow line. This phenomenon is called 'Cell Pinball'. Through visualization, we found that the RBC being in Cell Pinball mode rotates around the perpendicular axis to the flow line and the rotating direction has one-to-one relationship with the moving direction without any exceptions. We also found that the rotating axis exists slightly behind the center of gravity with respect to the flow direction. This geometrical configuration makes an unstable condition for the cell under the fluid force, which eventually produces the motion perpendicular to the main flow line.
    No preview · Article · Feb 2015 · Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)
  • Takeshi Hayakawa · Shinya Sakuma · Fumihito Arai
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    ABSTRACT: We present a novel cell manipulation method using vibration-induced local flow in open chip environment. By applying circular vibration to micropillars on a chip, local whirling flow is induced around the micropillars. From the observation of this unique phenomenon, we propose the concept of cell manipulation in open chip environment. We analyze this phenomenon theoretically, and evaluate the effect of the frequency and the amplitude of applied vibration. We design the micropillar array according to the analysis for transportation for oocytes. We apply the proposed method to transportation of mouse oocytes and confirm that the velocity of transportation is approximately 25 μm/s.
    No preview · Article · Feb 2015 · Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)
  • Y. Murozaki · S. Sakuma · F. Arai
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    ABSTRACT: We successfully established a wafer level fabrication process of the quartz crystal resonator (QCR) load sensor using atomic diffusion bonding. The proposed sensor has three-layer structures; two Si-hold layers and a quartz layer. Using microfabrication and atomic diffusion bonding, the assembly process was simplified. The fabrication process enables further miniaturization of the QCR sensor due to the simplified assembling method. The fabricated sensor is easily integrated in the outer package and can be designed the measurement range. Finally, we succeeded in multi-biosignals (heartbeat, body motion) detection using fabricated QCR sensor and the outer case.
    No preview · Article · Feb 2015 · Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)
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    ABSTRACT: An on-chip actuation transmitter for achieving fast and accurate cell manipulation is proposed. Instead of manipulating cell position by a directly connected macro-scale pump, polydimethylsiloxane deformation is used as a medium to transmit the actuation generated from the pump to control the cell position. This actuation transmitter has three main advantages. First, the dynamic response of cell manipulation is faster than the conventional method with direct flow control based on both the theoretical modeling and experimental results. The cell can be manipulated in a simple harmonic motion up to 130 Hz by the proposed actuation transmitter as opposed to 90 Hz by direct flow control. Second, there is no need to fill the syringe pump with the sample solution because the actuation transmitter physically separates the fluids between the pump and the cell flow, and consequently, only a very small quantity of the sample is required (<1 μl). In addition, such fluid separation makes it easy to keep the experiment platform sterilized because there is no direct fluid exchange between the sample and fluid inside the pump. Third, the fabrication process is simple because of the single-layer design, making it convenient to implement the actuation transmitter in different microfluidic applications. The proposed actuation transmitter is implemented in a lab-on-a-chip system for red blood cell (RBC) evaluation, where the extensibility of red blood cells is evaluated by manipulating the cells through a constriction channel at a constant velocity. The application shows a successful example of implementing the proposed transmitter.
    No preview · Article · Feb 2015 · Biomicrofluidics
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    ABSTRACT: The highly pathogenic avian influenza (AI) virus, H5N1, is a serious threat to public health worldwide. Both the currently-circulating H5N1 and previously-circulating AI viruses recognize avian-type receptors; however, only the H5N1 is highly infectious and virulent in humans. The mechanism(s) underlying this difference in infectivity remains unclear. The aim of the present study was to clarify the mechanisms responsible for the difference in infectivity between the currently- and previously-circulating strains. Primary human small airway epithelial cells (SAECs) were transformed with the SV40 large T-antigen to establish a series of clones (SAEC-Ts). These clones were then used to test the infectivity of AI strains. Human SAEC-Ts could be broadly categorized into two different types based on their susceptibility (high or low) to the viruses. SAEC-T clones were poorly susceptible to previously-circulating AI, but were completely susceptible to the currently-circulating H5N1. The hemagglutinin (HA) of the current H5N1 virus showed greater membrane fusion activity at higher pH levels than that of previous AI viruses, resulting in broader cell tropism. On the other hand, the endosomal pH was lower in high-susceptibility SAEC-T clones than that in low-susceptibility SAEC-T clones. Taken together, the results of the present study suggest that the infectivity of AI viruses, including H5N1, depends upon a delicate balance between the acid sensitivity of the viral HA and the pH within the endosomes of the target cell. Thus, one of the mechanisms underlying H5N1 pathogenesis in humans relies on its ability to fuse efficiently with the endosomes in human airway epithelial cells. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    No preview · Article · Feb 2015 · Journal of Biological Chemistry
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    ABSTRACT: In the drug discovery and regenerative medicine research, in vitro models based on cells or tissues are widely desired for attaining reliable data and high throughput as well as ethical concerns. This model: “bionic simulator” is required to simulate the biological function in the context of whole living organs. In this chapter, to achieve an organ-explant-chip for evaluating the function of an explanted biological organ by the mechanical system, we focused on the connection technique because we need to reconstruct the explanted organs or tissues as part of the biological simulator by connecting them with the external environment, other organs, and tissues. By using this microfluidic device, we have succeeded in constructing a hybrid circulatory system between artificial tubes and the explanted heart. Moreover, we have succeeded in measuring the response of the explanted heart with a variety of solutions. We confirmed from the response of the explanted heart to agonist drugs that the explanted organ maintained normal function.
    No preview · Article · Jan 2015
  • C.-H.D. Tsai · Shinya Sakuma · Fumihito Arai · Makoto Kaneko
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    ABSTRACT: This chapter covers dimensionless evaluation for the stiffness-based deformability of a cell using a high-resolution vision system and a microchannel. In conventional approaches, the transit time of a cell through a microchannel is often utilized for the evaluation of cell deformability. However, such time includes both the information of cell stiffness and viscosity. In this work, we eliminate the effect from cell viscosity, and focus on the cell stiffness only. We find that the velocity of a cell varies when enters a channel, and eventually reaches to equilibrium where the velocity becomes constant. The constant velocity is defined as the equilibrium velocity of the cell, and it is utilized to define the observability of stiffness based deformability. The necessary and sufficient numbers of sensing points for evaluating stiffness-based deformability are discussed. Through the dimensional analysis on the microchannel system, three dimensionless parameters determining stiffness-based deformability are derived, and a new index is introduced based on these parameters. The experimental study is conducted on the red blood cells from a healthy subject and a diabetic patient. With the proposed index, we showed that the experimental data can be nicely arranged.
    No preview · Article · Jan 2015
  • Fumihito Arai · Shinya Sakuma
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    ABSTRACT: In this chapter, we propose “on-chip robotics” that is based on robot technologies and lab-on-a-chip devices to achieve high-speed, high-accuracy, and quantitative cell manipulation and analysis on a chip. We presents a high-throughput cell mechanical characterization method using a robot integrated microfluidic chip (robochip). The robochip contains a magnetically driven on-chip probe, a force sensor, and microchannels. The displacement reduction mechanism is adopted to the on-chip probe for high resolution positioning of the tip of the probe, and we achieved noncontact actuation of the on-chip probe with 0.18 μm in repetitive positioning. We show the automated mechanical characterization of oocyte. The throughput of the measurement is approximately 15–20 s per oocyte, and we conclude that high-throughput cellular mechanical characterization is achieved. We also show measurements of the viscoelastic properties of oocyte using the robochip. The proposed approach based on a robochip is a promising technology for contributing to the analysis of the physical and biological properties of cells.
    No preview · Article · Jan 2015

Publication Stats

6k Citations
322.09 Total Impact Points

Institutions

  • 1991-2015
    • Nagoya University
      • • Department of Mechanical Science and Engineering
      • • Department of Micro-Nano Systems Engineering
      Nagoya, Aichi, Japan
    • Tokyo University of Science
      • Department of Mechanical Engineering (School of Engineering)
      Edo, Tōkyō, Japan
    • Kisarazu National College of Technology
      Kizarazu, Chiba, Japan
  • 2011
    • Seoul National University
      • Department of Materials Science and Engineering
      Sŏul, Seoul, South Korea
    • Juntendo University
      • Division of Gastroenterology
      Edo, Tōkyō, Japan
    • Fujita Health University
      • Department of Neurosurgery
      Nagoya, Aichi, Japan
  • 2005-2010
    • Tohoku University
      • • Department of Bioengineering and Robotics
      • • Graduate School of Dentistry
      Sendai-shi, Miyagi-ken, Japan
  • 2008
    • Hosei University
      • Division of Frontier Bioscience
      Edo, Tōkyō, Japan
  • 2003-2004
    • Samsung Advanced Institute of Technology
      Usan-ri, Gyeonggi-do, South Korea
    • University of the Philippines Manila
      Manila, National Capital Region, Philippines
  • 2001
    • Fujitsu Ltd.
      Kawasaki Si, Kanagawa, Japan
  • 1997-1999
    • Shinryo Corporation
      Edo, Tokyo, Japan
  • 1996
    • Mie University
      • Department of Mechanical Engineering
      Tsu-shi, Mie-ken, Japan
  • 1992-1993
    • Kinjo Gakuin University
      Nagoya, Aichi, Japan