Published papers

Cell agglomeration is essential both to the success of drug testing and to the development of tissue engineering. Here, a MHz-order acoustic wave is used to generate acoustic streaming in the wells of a 24-well plate to drive particle and cell agglomeration. Acoustic streaming is known to manipulate particles in microfluidic devices, and even provide concentration in sessile droplets, but concentration of particles or cells in individual wells has never been shown, principally due to the drag present along the periphery of the fluid in such a well. The agglomeration time for a range of particle sizes suggests that shear-induced migration plays an important role in the agglomeration process. Particles with a diameter of 45 mu m agglomerated into a suspended pellet under exposure to 2.134 MHz acoustic waves at 1.5 W in 30 s. Additionally, BT-474 cells also agglomerated as adherent masses at the center bottom of the wells of tissue-culture treated 24-well plates. By switching to low cell binding 24-well plates, the BT-474 cells formed suspended agglomerations that appeared to be spheroids, fully fifteen times larger than any cell agglomerates without the acoustic streaming. In either case, the viability and proliferation of the cells were maintained despite acoustic irradiation and streaming. Intermittent excitation was effective in avoiding temperature excursions, consuming only 75 mW per well on average, presenting a convenient means to form fully three-dimensional cellular masses potentially useful for tissue, cancer, and drug research.

Cellular aggregates that mimic cell–cell interactions in vitro are essential for biological research. This study introduces a method to form large scaffold-free 3-D aggregates in a clinically ubiquitous cell culture dish using kilohertz-order ultrasound standing wave trapping (USWT). We fabricated an aggregate formation system in which a 60-mm dish was set above a Langevin transducer via water. The transducer was excited at 110.8 kHz, and then C2C12 myoblasts were injected into the dish and trapped at the node position of the standing wave. The diameter and thickness of the formed aggregate were 8 and 2.7 mm, respectively, which are larger than those of aggregates formed previously by USWT. Moreover, we confirmed that >94% of cells constituting the aggregates survived 9 h, and the protein expression of cells was not altered significantly. This method can be applied to form aggregates with high functionality, which contributes to the development of biological research methodology.

Cell detachment is essential in culturing adherent cells. Trypsinization is the most popular detachment technique, even though it reduces viability due to the damage to the membrane and extracellular matrix. Avoiding such damage would improve cell culture efficiency. Here we propose an enzyme-free cell detachment method that employs the acoustic pressure, sloshing in serum-free medium from intermittent traveling wave. This method detaches 96.2% of the cells, and increases its transfer yield to 130% of conventional methods for 48 h, compared to the number of cells detached by trypsinization. We show the elimination of trypsinization reduces cell damage, improving the survival of the detached cells. Acoustic pressure applied to the cells and media sloshing from the intermittent traveling wave were identified as the most important factors leading to cell detachment. This proposed method will improve biopharmaceutical production by expediting the amplification of tissue-cultured cells through a more efficient transfer process.

円柱状振動子の縦振動と横振動を用いた多自由度超音波モータを実現した．すなわち，円柱の固有振動モードのうち振動方向が互いに直交し，縮退する縦振動と2つの横振動を適当な位相差をもって励振し，振動子先端に直交3軸回りの楕円運動を生成すると，振動子先端に接触した球状回転子は上記軸回りに多自由度回転される．本研究では，駆動原理の提案，有限要素法を用いた振動設計およびプロトタイプによる駆動確認を行った．

円柱状振動子の縦振動と曲げ振動を用いた多自由度超音波モータを実現した．すなわち，円柱の固有振動モードのうち振動方向が互いに直交し，縮退する縦振動と2つの曲げ振動を適当な位相差をもって励振し，振動子先端に直交3軸回りの楕円運動を生成すると，振動子先端に接触した球状回転子は上記軸回りに多自由度回転される．本研究では，駆動原理を提案し，プロトタイプによって原理を確認した．

本研究では，物体との接触／非接触によって力／位置のフィードバックが切り替えられるパッシブフォースフィードバック制御法を提案した．また，本制御法を用いて複雑な手指動作のテレオペレーションを実現する多指エクゾスケルトン型ハプティックデバイスを開発した．本デバイスは，操作者の指先端に接続したリンクとリンク根元部に配置されたクラッチから構成される．操作者に反力を提示する際にはクラッチによるリンク全体の固定とデバイス内の弾性要素の変形を利用する．

A novel control, methodology for master-slave systems using passive force feedback has been proposed by the authors. The methodology solves the conventional problems of previously developed master-slave systems with force feedback, such as oscillations, complex structures and complicated control algorithm. In the present paper a multi-fingered exoskeleton haptic device (master hand) with passive force feedback function is developed. First, the exoskeleton master hand with three fingers (12 degrees of freedom) is designed and implemented. Each finger of the master hand consists of a link mechanism with elastic-shaft joints and clutches. Using link mechanisms, the master hand measures fingertip positions and angles of index finger middle finger and thumb. Furthermore, it also enables passive force feedback to an operator by the same link mechanism used for the geometric measurements. Then, a virtual reality system of human hand is constructed using the master hand and the control methodology. Using the system, sensory evaluations are conducted on human subjects to confirm the usability of the developed master hand and the possibility of the control methodology in the virtual reality system. As a result, the subjects possibly recognize the stiffness of the objects in the virtual environment.

dA multi-DOF ultrasonic motor developed by the authors is capable of generating multi-DOF rotation of a spherical rotor using three orthogonal natural vibrations of a bar-shaped stator. The ultrasonic motor is suitable for making small, light weight and simple multi-DOF motion unit. In the present paper, a control methodology for the multi-DOF ultrasonic motor is proposed and a motion control test using the method is conducted. First, an inverse model of the multi-DOF ultrasonic motor is developed using our prior knowledge in ultrasonic motors and neural network technique in order to deal with the redundancy and non-linearity of driving characteristics. Second, a novel control method using the inverse model is proposed. Then, motion control tests are conducted to confirm the ability of the proposed control method. The results confirm that the rotor can be rotated around arbitrary rotational axis using the inverse model, and that the proposed control method does work successfully.

A new type of master-slave control methodology, which has the merits of both unilateral and bilateral ones, is proposed. The methodology is built on switching the unilateral feedback controls of position and force as required using switching and elastic elements. Proposed methodology not only eliminates the demerits of bilateral control, but also supplies the mechanical force feedback to the operator. It utilizes a feature of human factor that direct displacement feedback is not as important as visual and force feedback. Effectiveness of the proposed method is confirmed by experiments using a developed simple single axis master-slave arm system. Driving test of the experimental devices and sensory evaluations are conducted. As a result, it is confirmed that the methodology successfully provides the sense of touch to the operator of the system.