F. Arai

Nagoya University, Nagoya, Aichi, Japan

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Publications (644)252.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, a novel multi-fluorescent micro-sensor that can respond to both pH and temperature was designed and synthesized. It is based on amino-polystyrene microbeads, and two different fluorescent indicators (Rhodamine B and Fluorescein isothiocyanate) were used simultaneously to synthesize the fluorescent micro-sensor. Rhodamine B was embedded inside the amino-polystyrene microbeads, whereas Fluorescein isothiocyanate (FITC) was used to modify the surface of the beads. Because of the different fluorescence wavelengths and measurement positions of FITC and Rhodamine B, interference from each fluorescent indicator should be avoided. The fluorescence responses of FITC and Rhodamine B to pH and temperature, respectively, were detected. Rhodamine B demonstrates an excellent linear relationship between relative fluorescence intensity and temperature, while the relative fluorescence intensity was found to be independent of the pH. The calibrated sensitivity of Rhodamine B is −3.4%/°C, with a temperature accuracy of 0.1 °C. Therefore, changes in the temperature information can be calibrated based on the relative fluorescence intensity changes in Rhodamine B. On the other hand, FITC is sensitive to both pH and temperature. We propose a temperature compensation method for pH calibration. After temperature compensation, the pH accuracy calibrated based on the pH sensitivity of FITC improves from 1.5 to 0.2.
    Sensors and Actuators B Chemical 11/2014; 203:54–62. · 3.84 Impact Factor
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    ABSTRACT: Photoautotrophic bacteria have developed mechanisms to maintain K(+) homeostasis under changing ionic concentrations in the environment. Synechocystis sp. PCC 6803 contains genes encoding for a well-characterized Ktr-type K(+) uptake transporter (Ktr) and for a putative ATP-dependent transporter specific for K(+) (Kdp). The contributions of each of these K(+) transport systems to cellular K(+) homeostasis have not yet been defined conclusively. To verify the functionality of Kdp, kdp genes were expressed in E. coli, where Kdp conferred K(+) uptake albeit with lower rates than that of Ktr. The on-chip microfluidic device enabled to monitor the biphasic initial volume recovery of single Synechocystis cells after hyperosmotic shock. Here, Ktr functioned as the primary K(+) uptake system during the first recovery phase, whereas Kdp did not significantly contribute. Expression of the kdp operon was induced by extracellular K(+) depletion in Synechocystis. Correspondingly, Kdp-mediated K(+) uptake supported the cell growth at trace amounts of external potassium. This induction of kdp expression depended on two adjacent genes, hik20 and rre19, encoding for a putative two-component system. The circadian expression of kdp and ktr peaked at subjective dawn, which may support the acquisition of K(+) required for the regular diurnal photosynthetic metabolism. These results indicate that Kdp contributes to maintain a basal intracellular K(+) concentration at limited K(+) in natural environments, whereas Ktr mediates fast potassium movements in the presence of higher K(+) availability. Through their distinct activities both Ktr and Kdp coordinate the responses of Synechocystis to changes in K(+) levels under fluctuating environmental conditions.
    Journal of bacteriology. 10/2014;
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    ABSTRACT: A microfluidic design for evaluating red blood cell deformability with geometrical alignment mechanism is proposed. While the transit velocity of a cell passing through a constriction channel is conventionally utilized as an index of cell deformability, the flow-in angle of the cell entering the channel is found affecting the transit significantly, and would interfere with the evaluation. To suppress such kind of interference, an additional alignment channel is placed in front of the evaluation channel for aligning target cells before entering the evaluation channel. Cells are spontaneously aligned by the geometrical constraints without any additional control. The Experiments on the red blood cells from three healthy subjects and a patient with multiple myeloma are conducted. According to the experimental results, the alignment channel effectively reduce 42.7% of position distribution in average, and the negative correlation between transit velocity and cell size is increased. The correlation shows the improved size sensitivity of the proposed method. For the purpose of comparison and validating the microchannel approach, the stiffness of the subjects' red blood cells is also measured by an atomic force microscope, the current gold standard of cell stiffness measurement. The results from two approaches show the same tendency of the RBC deformability, which evidently support the validity of the proposed method on cell deformability evaluation.
    RSC Advances 09/2014; · 3.71 Impact Factor
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    ABSTRACT: We propose a novel on-chip enucleation of an oocyte with zona pellucida by using a combination of untethered microrobots. To achieve enucleation within the closed space of a microfluidic chip, two microrobots, a microknife and a microgripper were integrated into the microfluidic chip. These microrobots were actuated by an external magnetic force produced by permanent magnets placed on the robotic stage. The tip of the microknife was designed by considering the biological geometric feature of an oocyte, i.e. the oocyte has a polar body in maturation stage II. Moreover, the microknife was fabricated by using grayscale lithography, which allows fabrication of three-dimensional microstructures. The microgripper has a gripping function that is independent of the driving mechanism. On-chip enucleation was demonstrated, and the enucleated oocytes are spherical, indicating that the cell membrane of the oocytes remained intact. To confirm successful enucleation using this method, we investigated the viability of oocytes after enucleation. The results show that the production rate, i.e. the ratio between the number of oocytes that reach the blastocyst stage and the number of bovine oocytes after nucleus transfer, is 100%. The technique will contribute to complex cell manipulation such as cell surgery in lab-on-a-chip devices.
    Journal of Micromechanics and Microengineering 07/2014; 24(9):095004. · 1.79 Impact Factor
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    ABSTRACT: Mammalian cells must produce heat to maintain body temperature and support other biological activities. Methods to measure a cell's thermogenic ability by inserting a thermometer into the cell or measuring the rate of oxygen consumption in a closed vessel can disturb its natural state. Here, we developed a noninvasive system for measuring a cell's heat production with a bimaterial microcantilever. This method is suitable for investigating the heat-generating properties of cells in their native state, because changes in cell temperature can be measured from the bending of the microcantilever, without damaging the cell and restricting its supply of dissolved oxygen. Thus, we were able to measure increases in cell temperature of <1 K in a small number of murine brown adipocytes (n = 4-7 cells) stimulated with norepinephrine, and observed a slow increase in temperature over several hours. This long-term heat production suggests that, in addition to converting fatty acids into heat energy, brown adipocytes may also adjust protein expression to raise their own temperature, to generate more heat. We expect this bimaterial microcantilever system to prove useful for determining a cell's state by measuring thermal characteristics.
    Biophysical journal. 06/2014; 106(11):2458-2464.
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    ABSTRACT: Background Microcannulation, a surgical procedure for the eye that requires drug injection into a 60–90 µm retinal vein, is difficult to perform manually. Robotic assistance has been proposed; however, its effectiveness in comparison to manual operation has not been quantified.Methods An eye model has been developed to quantify the performance of manual and robotic microcannulation. The eye model, which is implemented with a force sensor and microchannels, also simulates the mechanical constraints of the instrument's movement. Ten subjects performed microcannulation using the model, with and without robotic assistance.ResultsThe results showed that the robotic assistance was useful for motion stability when the drug was injected, whereas its positioning accuracy offered no advantage.Conclusions An eye model was used to quantitatively assess the robotic microcannulation performance in comparison to manual operation. This approach could be valid for a better evaluation of surgical robotic assistance. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Medical Robotics and Computer Assisted Surgery 04/2014; · 1.49 Impact Factor
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    ABSTRACT: Red blood cells (RBC) circulate the human body several hundred thousand times in their life span. Therefore, their deformability is really important, especially when they pass through a local capillary whose diameter can be as narrow as 3 μm. While there have been a number of works discussing the deformability in a simulated capillary such as a microchannel, as far as we examined in the literature, no work focusing on the change of shape after reciprocated mechanical stress has been reported so far. One of the reasons is that there have been no appropriate experimental systems to achieve such a test. This paper presents a new concept of RBC fatigue evaluation. The fatigue state is defined by the time of reciprocated mechanical stress when the extensibility and the recoverability characteristics meet each other. Our challenge is how to construct a system capable of achieving stable and accurate control of RBCs in a microchannel. For this purpose, we newly introduced two fundamental components. One is a robotic pump capable of manipulating a cell in the accuracy of ±0.24 μm in an equilibrium state with a maximum response time of 15 ms. The other is an online high speed camera capable of chasing the position of RBCs with a sampling rate of 1 kHz. By utilizing these components, we could achieve continuous observation of the length of a RBC over a 1000 times reciprocated mechanical stress. Through these experiments, we found that the repeat number that results in the fatigue state has a close correlation with extensibility.
    Lab on a Chip 01/2014; · 5.70 Impact Factor
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    ABSTRACT: This paper proposes a new index for evaluating the stiffness-based deformability of a cell using 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 paper, we eliminate the effect from cell viscosity, and focus on the cell stiffness only. We find that the velocity of a cell varies when it 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 diabetes patient. With the proposed index, we showed that the experimental data can be nicely arranged.
    IEEE Transactions on Biomedical Engineering 01/2014; 61(4):1187-1195. · 2.35 Impact Factor
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    ABSTRACT: How to preserve the catheter without any modifications and improve the precision of manipulation in the catheter-based endovascular intervention remains a challenge for quantitative training and evaluation. This paper presents an optical sensor unit to measure catheter motions based on the working principle of Laser Doppler, which allows for catheter motion measurement with non-contact detection and supports medical training and evaluation without modifications on the catheter. Then, calibrate this sensor unit and implement recording of catheter motion. Next, propose a training system by tracking the reference trajectory based on an expert’s skill, and provide visual feedback to improve the precision of catheter manipulation. Eight subjects were trained for catheter manipulation with this system. Among them, six subjects improved their catheter manipulation of linear motion, and seven improved the catheter rotational motion.
    Advanced Robotics 01/2014; 28(19). · 0.51 Impact Factor
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    ABSTRACT: Circulating tumor cells (CTCs) in the blood of patients with epithelial malignancies provide a promising and minimally invasive source for early detection of metastasis, monitoring of therapeutic effects and basic research addressing the mechanism of metastasis. In this study, we developed a new filtration-based, sensitive CTC isolation device. This device consists of a 3-dimensional (3D) palladium (Pd) filter with an 8 µm-sized pore in the lower layer and a 30 µm-sized pocket in the upper layer to trap CTCs on a filter micro-fabricated by precise lithography plus electroforming process. This is a simple pump-less device driven by gravity flow and can enrich CTCs from whole blood within 20 min. After on-device staining of CTCs for 30 min, the filter cassette was removed from the device, fixed in a cassette holder and set up on the upright fluorescence microscope. Enumeration and isolation of CTCs for subsequent genetic analysis from the beginning were completed within 1.5 hr and 2 hr, respectively. Cell spike experiments demonstrated that the recovery rate of tumor cells from blood by this Pd filter device was more than 85%. Single living tumor cells were efficiently isolated from these spiked tumor cells by a micromanipulator, and KRAS mutation, HER2 gene amplification and overexpression, for example, were successfully detected from such isolated single tumor cells. Sequential analysis of blood from mice bearing metastasis revealed that CTC increased with progression of metastasis. Furthermore, a significant increase in the number of CTCs from the blood of patients with metastatic breast cancer was observed compared with patients without metastasis and healthy volunteers. These results suggest that this new 3D Pd filter-based device would be a useful tool for the rapid, cost effective and sensitive detection, enumeration, isolation and genetic analysis of CTCs from peripheral blood in both preclinical and clinical settings.
    PLoS ONE 01/2014; 9(2):e88821. · 3.53 Impact Factor
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    ABSTRACT: There are several complications associated with Stent-assisted Coil Embolization (SACE) in cerebral aneurysm treatments, due to damaging operations by surgeons and undesirable mechanical properties of stents. Therefore, it is necessary to develop an in vitro simulator that provides both training and research for evaluating the mechanical properties of stents. A new in vitro simulator for three-dimensional digital subtraction angiography was constructed, followed by aneurysm models fabricated with new materials. Next, this platform was used to provide training and to conduct photoelastic stress analysis to evaluate the SACE technique. The average interaction stress increasingly varied for the two different stents. Improvements for the Maximum-Likelihood Expectation-Maximization method were developed to reconstruct cross-sections with both thickness and stress information. The technique presented can improve a surgeon's skills and quantify the performance of stents to improve mechanical design and classification. This method can contribute to three-dimensional stress and volume variation evaluation and assess a surgeon's skills. Copyright © 2013 John Wiley & Sons, Ltd.
    International Journal of Medical Robotics and Computer Assisted Surgery 12/2013; · 1.49 Impact Factor
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    ABSTRACT: For the present study, we have successfully fabricated a novel cylinder-shaped device that is able to produce mono-dispersed plasma bubbles under atmospheric pressure and water environment. The generated plasma has characteristics of low temperature, which was generated by dielectric discharge barrier. Also, the plasma bubble has been successfully transported downstream with distance of 1.20 [cm].
    2013 International Symposium on Micro-NanoMechatronics and Human Science (MHS); 11/2013
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    ABSTRACT: In this research, we demonstrated a microfluidic chip to pretreat the samples for viral genome assay. The microfluidic chip has the following three functions; (1) Virus purification and enrichment, (2) Viral RNA extraction, and (3) Capture of the targeted virus genome. Hydroxyapatite chromatography, Boom method, and PNA (Peptide Nucleic Acid) were used for the above three functions, respectively. These three functions were integrated in one chip. Furthermore PNA immobilized on the glass can detect the targeted virus genome so that in situ virus detection would be possible by anybody, anywhere, anytime.
    2013 International Symposium on Micro-NanoMechatronics and Human Science (MHS); 11/2013
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    ABSTRACT: In this paper, we developed transfection of a single fluorescent nanosensor into a cell nucleus using step-wise fusion of liposome for cellular temperature measurement. The single fluorescent temperature nanosensor is included in the multi lamellar liposomes using Layer-by-Layer formation. The sensor is manipulated by optical tweezers and transfected into the cell or cell nucleus by membrane fusion. To achieve this, a nanotechnology was developed that creates a multi lamellar liposome, which we refer to as Layer-by-Layer absorbed lipid membrane (LBL Lipsome). We also evaluated measurement size and surface charge of multi-layered liposome by the method of resistive pulse sensing. We demonstrated the fabrication of the liposome containing single sensor, immobilization of the sensor to cellular membrane, and transfection of the sensor into the cell cytoplasm and nucleus.
    2013 IEEE 13th International Conference on Nanotechnology (IEEE-NANO); 08/2013
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    ABSTRACT: We proposed measurement of thermal conductivity of a single carbon nanotube (CNT) using fluorescence temperature sensor in liquid and air. The sensor containing fluorescence dye is used for fixation of CNT, local heat by Joule-heating, and measurement of temperature distribution. The CNT is fixed to the sensors during photofabrication. Thermal conductivity of the fixed CNT is evaluated by the temperature difference between the both ends of CNT, heat quantity of input to the CNT. In this paper, we demonstrated fabrication of evaluation system using photolithography and measurement of thermal conductivity of the single CNT in liquid and air condition. As experimental results, calculated thermal conductivity of the CNT in air (765 ± 45 [W/mK]) is higher than that of the CNT in water (489 ± 60 [W/mK]).
    2013 IEEE 13th International Conference on Nanotechnology (IEEE-NANO); 08/2013
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    ABSTRACT: The effect of osmotic condition on a living cell inside a micro-channel is firstly studied in this work. By utilizing a high-speed camera, we observed distinct patterns of cell motion under different osmotic conditions, which are established by saline with different concentrations of sodium chloride (NaCl). The cell motions are tracked by a computer, and are presented by the coordinates of location and time (x-t chart). The motions of cells under hypotonic condition (NaCl% < 0.9%) are convex curves on the chart while the ones under isotonic and hypertonic conditions (NaCl% ≥ 0.9%) are concave curves. Since saline is widely used in both medical practices and cell-related researches, our results point out two important facts: 1) Cells are sensitive to the percentage of NaCl. One percent difference in overall concentration makes dramatic changes in cell characteristics, such as cell stiffness. 2) The micro-channel method can clearly tell the difference between hypotonic, isotonic and hypertonic conditions according to the pattern of cell motion. Interpretations of the phenomena from different perspectives are also discussed in this paper.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:5525-5528.
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    ABSTRACT: We have previously reported our attempt to propel microbbles in flow by a primary Bjerknes force, which is a physical phenomenon where an acoustic wave pushes an obstacle along its direction of propagation. However, when ultrasound was emitted from surface of the body, controlling bubbles in against flow was needed. It is unpractical to use multiple transducers to produce the same number of focal points because single element transducer cannot produce more than two focal points. In this study, we introduced a complex artificial blood vessel according to a capillary model and a 2D array transducer to produce multiple focal points for active control of microbubbles in against flow. Furthermore, we investigated bubble control in viscous fluid. As the results, we confirmed clearly path selection of MBs in viscous fluid as well as in water.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:6277-6280.
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    ABSTRACT: We previously reported our attempt to propel microbubbles in a flow by a primary Bjerknes force, which is a physical phenomenon where an acoustic wave pushes an obstacle along its direction of propagation. However, when ultrasound was emitted from the surface of the body, controlling bubbles in an against-flow was necessary. It is unpractical to use multiple transducers to produce the same number of focal points because single-element transducers cannot produce more than two focal points. In this study, we introduced a complex artificial blood vessel according to a capillary model and a two-dimensional (2D) array transducer to produce multiple focal points for the active control of microbubbles in an against-flow. From the results, about 15% more microbubbles were led to the desired path with multiple focal points of ultrasound relative to the no-emission case.
    Japanese Journal of Applied Physics 07/2013; 52(7). · 1.07 Impact Factor
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    ABSTRACT: We previously reported our attempts at the active control of microbubble aggregations using acoustic radiation force, which propels microbubbles and adjusts the size of aggregations. However, because we used simple-shape artificial blood vessels, the behavior of aggregations in a small channel, e.g., the probability to obstruct the bloodstream, and the possibility of embolization, has not been predicted. Thus, we designed and fabricated a multi-bifurcated artificial blood vessel to apply to the production and active control of microbubble aggregations. Then, we introduced two kinds of ultrasound transducers for producing and propelling aggregations. First, we produced aggregations in a flow to measure their size and investigate their variation according to the emission duration of ultrasound. Then, we control the aggregations in an artificial blood vessel to verify their controllability. When ultrasound was stopped, the aggregations flaked off the vessel wall and flowed downstream, were propelled to the desired path, and finally were caught at a narrow path. We verified the same experiment under similar parameters to calculate the probability of realizing a path block. When the flow velocity was 20 mm/s, almost 50% of the aggregations were induced to flow through the desired path and a maximum probability of realizing a path block of 86% was achieved with the formation of aggregations.
    Japanese Journal of Applied Physics 07/2013; 52(7). · 1.07 Impact Factor
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    ABSTRACT: In this study, we developed a microfluidic chip with a magnetically driven microrobot for oocyte enucleation. A microfluidic system was specially designed for enucleation, and the microrobot actively controls the local flow-speed distribution in the microfluidic chip. The microrobot can adjust fluid resistances in a channel and can open or close the channel to control the flow distribution. Analytical modeling was conducted to control the fluid speed distribution using the microrobot, and the model was experimentally validated. The novelties of the developed microfluidic system are as follows: (1) the cutting speed improved significantly owing to the local fluid flow control; (2) the cutting volume of the oocyte can be adjusted so that the oocyte undergoes less damage; and (3) the nucleus can be removed properly using the combination of a microrobot and hydrodynamic forces. Using this device, we achieved a minimally invasive enucleation process. The average enucleation time was 2.5 s and the average removal volume ratio was 20%. The proposed new system has the advantages of better operation speed, greater cutting precision, and potential for repeatable enucleation.
    06/2013; 4:272-285.

Publication Stats

4k Citations
252.93 Total Impact Points


  • 1991–2014
    • Nagoya University
      • • Department of Mechanical Science and Engineering
      • • Department of Micro-Nano Systems Engineering
      Nagoya, Aichi, Japan
    • Kisarazu National College of Technology
      Kizarazu, Chiba, Japan
  • 2013
    • Kyushu Institute of Technology
      Kitakyūshū, Fukuoka, Japan
  • 2005–2012
    • Tohoku University
      • • Graduate School of Engineering
      • • Department of Bioengineering and Robotics
      • • Graduate School of Dentistry
      Sendai-shi, Miyagi-ken, Japan
  • 2010
    • Osaka University
      • Department of Mechanical Engineering
      Ōsaka-shi, Osaka-fu, Japan
  • 2007
    • Purdue University
      • School of Industrial Engineering
      West Lafayette, IN, United States
  • 2006
    • Toyama Prefectural University
      • Division of Intelligent Systems Design Engineering
      Toyama-shi, Toyama-ken, Japan
  • 1998–2004
    • Nagoya Institute of Technology
      Nagoya, Aichi, Japan
    • The University of Electro-Communications
      Edo, Tōkyō, Japan
  • 2003
    • University of the Philippines Manila
      Manila, National Capital Region, Philippines
    • Samsung Advanced Institute of Technology
      Usan-ri, Gyeonggi Province, South Korea
  • 2002
    • Kobe University
      Kōbe, Hyōgo, Japan
  • 2000
    • Fisheries Research Agency
      Yokohama, Kanagawa, Japan
  • 1997–1999
    • Shinryo Corporation
      Edo, Tōkyō, Japan
  • 1996
    • Mie University
      • Department of Mechanical Engineering
      Tsu-shi, Mie-ken, Japan