We present a high-speed vision-based morphological analysis system for fast-flowing cells in a microchannel. Real-time video processing is performed in hardware logic by extracting the moment features and bounding boxes of multiple cells in 512 × 256-pixel images at 2000 fps. The extracted cell regions are pushed into a first-in-first-out (FIFO) buffer for real-time image-based morphological analysis after being shrunk proportionally to a certain size. By extracting the bounding boxes of the cell regions using hardware logic and shrinking the cell region to a certain size to reduce processing time, our high-speed vision system can perform fast morphological analysis of cells at 500 cells/s in fast microchannel flows. Moreover, snapshots of all passed cells under the microscope are stored for offline verification. The results of real-time experiments conducted to analyze the size, eccentricity, and transparency of sea urchin embryos flowing fast in microchannels verify the efficacy of our vision-based cell analysis system.

We propose a microrobotic platform that stimulates swimming microorganisms in a microfluidic chip with high speed and accuracy. The developed platform comprises (1) high-speed microrobots that can generate a millinewton-level driving force, micrometer-level positioning accuracy, and a millimeter per second level drive speed through the actuation of motorized stages with permanent magnets and (2) high-speed online vision sensor capable of capturing images on the order of 1000 frames per second. The specific design and architecture of the proposed platform are also presented. The proposed platform stimulates and observes swimming microorganisms in a microfluidic chip through a mechanical approach. This platform provides on-chip investigation with high functionality that has been difficult to achieve with previous approaches and contributes towards the discovery of previously unknown functions of swimming microorganisms in the bioscience fields.

Microrobots are promising tools for the treatment of biological cells because of their lack of skill dependence, high throughput, and high repeatability. Integration of a microfluidic chip and robotics based on microelectromechanical systems technology is a key challenge for biomedical innovations. In addition to the advantage of environmental control by a microfluidic chip, robots enable physical operations on the cell with high throughput. This paper presents high-speed microrobotic actuation driven by permanent magnets in a microfluidic chip. The developed microrobot has a milli-Newton-level output force from a permanent magnet, micrometer-level positioning accuracy, and drive speed of over 280 mm/s. The riblet surface, which is a regularly arrayed V-groove, reduces fluid friction and enables high-speed actuation. Ni and Si composite fabrication was employed to form the optimum riblet shape on the microrobot's surface by wet and dry etching. The evaluation experiments show that the microrobot can be actuated at a rate of up to 90 Hz, which is more than ten times higher than that of the microrobot without a riblet. Two distinguish applications of the developed microrobots were demonstrated in a microfluidic chip.

A new concept of μ-cell fatigue test is proposed. By reciprocating a cell across the throat of a micro channel repeatedly, the dynamic deformation behavior of the cell is measured. We define a new index of fatigue characteristics of cells as the number of reciprocatory motion leading to a prescribed recovery ratio. The test system is composed of a piezoelectric (PZT) actuator, a high speed vision sensor and a micro channel with a throat. Preliminary experiments were conducted by using Red Blood Cells (RBCs). The result suggested that the activation level of a cell can be evaluated based on its fatigue characteristics.

This paper presents the high speed microrobot actuation driven by permanent magnets in a microfluidic chip. The riblet surface, which is regularly arrayed V groove reduces the fluid friction and enables stable actuation in high speed. The comprehensive analysis of fluid force, the optimum design and its fabrication were conducted and proved the friction reduction by riblet. The Ni and Si composite fabrication was employed to form the optimum riblet shape on the microrobot surface by wet and dry etching. The evaluation experiments show the microrobot can actuate up to 90 Hs, which is 10 times higher than the original microrobot. In addition, it can be applied to cell manipulation without harm since the microrobot is covered by Si, which is bio-compatible. One of the applications of developed microrobot was demonstrated by assembling cell aggregation in high speed.

In this paper, we introduce an untethered type of magnetically driven microtool (MMT) with a force sensing function to investigate the stimulus characteristics of aquatic microorganisms in a microfluidic chip. The microchip is composed of the proposed MMTs, which have a Si-Ni hybrid structure, a transparent cover made of polydimethylsiloxane (PDMS), a glass substrate, and a microspacer to prevent both friction during the force measurement and damage to the micropattern of the MMT. The fabrication and drive performance of the MMT, which is actuated by permanent magnets from the outside of the microchip, verified in basic experiments. Finally, we succeeded in on-chip manipulation and sensing of microorganisms using this MMT, which we found to be easy to use.

In this study, we present a smooth enucleation process on a microfluidic chip. To improve the success rate of enucleation and increasing the potential viability of the enucleated oocyte, a microfluidic system is specially designed. Magnetically driven MicroTool (MMT) control the flow distribution in the microchamber. Designed microchannel with height difference is for the purpose of confining oocyte with its nucleus located in the withdrawal microchannel to achieve the high precision control in cutting volume. By utilizing these aspects, first, oocytes are sequentially loaded to the operation port; MMT constrains the oocyte location and controls the distribution of micro flow simultaneously letting hydraulic force cut off the nucleus from the oocyte. Enucleated oocyte is smooth in shape and incision is neat. With cutting volume control, this system can achieve high-speed enucleation with less cutting volume while removing the nucleus. Since the flow distribution could be managed by MMT significantly, therefore, the new system is proposed here to show advantages by the means of operation speed, cutting precision and great potentiality on continuous cutting process.

In this paper, we newly propose an organ-explanted bionic simulator (OBiS) using an isolated organ tissue. We use a heart isolated from the chick embryo for proposed simulator. To achieve the OBiS, we perform the concurrent microvascular anastomosis by using suction-induced vascular fixation (SVF) method for easily connection to artificial tubes with blood vessels led to the explanted chick's heart. Through the experiment with a simulated cardiovascular, it is confirmed that vessels can be aligned by using the proposed method. In addition, we have succeeded in connecting the Alg tubes with the blood vessels led to the heart of chick embryo. OBiS is available for the evaluation of new drugs immune response not only without using large animals but also as a response of organs beyond cellular level.

This paper describes an innovative driving method for magnetically driven microtools (MMT). 1.1 μm positioning accuracy of the MMT was obtained by applying a piezoelectric ceramic, which induced nanoscale vibration to the microfluidic chip, and reducing the friction on the MMT. Using this drive method, the enucleation process was conducted by dual-arm MMT. Permanent magnets are used to supply the driving power to the MMT allowing sufficient positioning accuracy to cut oocytes precisely. The nucleus was cut within 10 s, and the removed area was less than 25% of the original oocyte.

The video presents high power, high precision and high speed drive of on-chip robot and its biomedical applications. The magnetically driven microtool (MMT) actuated by permanent magnets was employed as a microrobot because of its strong output force in the order of millinewtons and the ultrasonic vibration was applied to the microfluidic chip in order to reduce the friction on the MMT. We have achieved 1.1 μm positioning accuracy of the MMT and applied this drive method to the enucleation of oocyte process. The dual-arm MMT removed the nucleus part in a few seconds.

In this paper, we newly propose an on-chip force sensing by using a magnetically driven microtool (MMT) equipped with a frame structure for measurement of stimulant property of Pleurosira laevis. The design and fabrication of the force sensing structure with a displacement magnification mechanism based on beam deformation is discussed. Through the basic experiments, the advantages of the proposed layer fabrication technique and the performance of the force sensor are confirmed. The basic characteristics of P. laevis are also confirmed by using the developed MMT.

In this paper, on-chip particle loading and dispensing modules are presented with their results for the automation of a single particle retrieving from a microfluidic channel. Our proposed microfluidic chip has several modules. Each one of them has important functions as (a) loading micro-particles singly to main microfluidic flow by the aid of magnetically driven microtools (MMT); (b) finding particle position in a microfluidic channel by micro-capacitance sensors; (c) adjusting micro-channel height locally by pneumatic pressure valve; (d) dispensing particles out from the microfluidic chip to incubation environment. Novelty of this paper is summarized as follows: (1) Multi-photoresist combination technique for the pneumatic pressure valve; (2) Automatic on-chip particle dispensing with micro-capacitance sensors. We showed feasibility of automatic dispensing of a single polystyrene bead (about 100 μm) from the chip to atmosphere. The performances of each module (hybrid structure, sensor and dispensing parts) were evaluated individually. We succeeded in determination of the movement of micro-particles (about 50-100 μm) with the velocity of over 6 mm/sec. by the micro-capacitance sensors. The advantages of the proposed system are that composed of the reusable drive system such as xy motorized stage, pumps and a disposable microfluidic chip.

In this paper, we discuss the design and fabrication approach to increase the success rate of single particle dispensing. Two pairs of capacitance sensors are placed in a biochip to detect the flow velocity of particles, and the air pressure is applied to eject particles by synchronizing the timing. Comprehensive design theory, which is taken into account of the back pressure caused by air pressure, the response time of the system, sensor property, and the delay of the dispensing from the air pressure, is developed in order to minimize the disturbance of the system and maximize the throughput of the ejection system. Then, the system has capability to eject 3 particles/sec and maximum flow velocity is 10 mm/s. The novelty of the system is that the biochip is disposable which is unlike the conventional mechanical inkjet system and it can prevent contamination. Therefore, the fabricated disposable biochip based on photolithography is low cost and the drive system is reusable. Finally, we succeed in automatic dispensing of a single particle (=100 µm) from a biochip to culture well atmosphere using developed cell ejection system with the success rate of 50 %.

This paper presents a force visualization mechanism for endoscopic surgical instruments using a Moirée fringe. This mechanism can display fringes or characters that correspond to the magnitude of a force between the surgical instruments and internal organs without the use of electronic elements, such as amplifiers and strain gauges. As this mechanism is simply attached to the surgical instruments, there is no need for additional devices in the operating room or wires to connect these devices. The structure is simple, and its fabrication is inexpensive. An example is shown with the mechanism mounted on a 10-mm forceps. We experimentally verified in vivo, using a pig, that it can display characters corresponding to the magnitude of the force, thus visually displaying the force even in endoscopic image.

This paper presents two innovative driving methodologies using magnetically driven microtools for precise cell manipulations and its automation systems. First, the magnetic analysis has been conducted to show the current MMT problem. Then, the new driving methodologies are introduced and backed up with FEM analysis and the experimental results. The positioning accuracy improves 3–10 times and the following response become 10 times higher against the driving linear stage. Using this methodology, the enucleation of oocytes is demonstrated to show the effectiveness of the method.

A big advantage of minimally invasive surgery is the quick recovery afforded by the minimal physical injury sustained by patients. However, the operative field provided by the endoscope camera is rather narrow. This paper discusses a new broad-view camera system, which is capable of providing a wider view of the internal organs during minimally invasive surgery. This system consists of a camera unit for capturing the image and a monitor for displaying the captured image. With the use of this system, the invasiveness of the procedure does not increase, and the other specifications of current minimally invasive surgery are maintained. Furthermore, it can function as a second camera (in addition to the one attached to the endoscope) and can help assess the overall state of the target area. In this paper, we present this a newly developed camera system, which is intended for use along with the proposed system. The camera system is composed of a miniature color CMOS camera, an indwelling needle, and an extra-thin connector. The specific design of the camera unit and the method for positioning it are shown here. The performance of this camera system has been confirmed through basic and laparoscopic surgery on animals.

This paper challenges the dynamic based diagnosis (see Fig. 1) of human eye. Through a high speed motion capture during an air jet applied to a human eye, the eye dynamics including stiffness and damping is evaluated. By utilizing both the eye pressure and the dynamic parameters, we can increase the reliability of the eye diagnosis. We show that each subject has his (or her) own impedance parameters and that stiffness is an important index for guaranteeing the validity of eye pressure sensing.

Conventional non-contact impedance sensors cause an essential sensing error in principle due to the intersection angle between the line of force probing and the sensing axis of distance sensor, especially for the environment with distributed compliance. To cope with the issue, we propose the co-axis type non-contact impedance sensor that can provide us with the accurate impedance parameters of environment. The key design is that we give the common axis for both force probing and distance sensor, so that we can obtain the exact displacement of environment. Experimental results are also shown for confirming the effectiveness of the proposed sensor.

We newly propose the Non-Contact Stiffness Imager that can provide us with the pattern of stiffness distribution of environment. It is composed of a force probe and a displacement sensor capable of obtaining area information. The main application of the Stiffness Imager is diagnosis, especially for examining whether there exist tissues suffered by disease or not. In order to show the effectiveness, we implement the Stiffness Imager into an endoscope camera for obtaining inner stiffness information as well as surface information of stomach. Basic experimental results are also shown.

This paper proposes a new endoscope system with an air injection based contact probe capable of measuring the local impedance of the inner surface of stomach. By utilizing air pressure, we can produce an equivalent contact force, which is really advantageous for avoiding any damage for stomach during an examination. A big issue is that there is no way to obtain the applied force to stomach exactly. The key for solving it is the specially designed solenoid valve with the response for more than 500 Hz. The solenoid valve with such a high response allows us to estimate each impedance parameter, even with a reference value. We show experimental system with a couple of interesting results.