Miniaturization of Respiratory Measurement System in Artificial Ventilator for Small Animal Experiments to Reduce Dead Space and Its Application to Lung Elasticity Evaluation.

A respiratory measurement system composed of pressure and airflow sensors was introduced to precisely control the respiratory condition during animal experiments. The flow sensor was a hot-wire thermal airflow meter with a directional detection and airflow temperature change compensation function based on MEMS technology, and the pressure sensor was a commercially available one also produced by MEMS. The artificial dead space in the system was minimized to the value of 0.11 mL by integrating the two sensors on the same plate (26.0 mm × 15.0 mm). A balloon made of a silicone resin with a hardness of A30 was utilized as the simulated lung system and applied to the elasticity evaluation of the respiratory system in a living rat. The inside of the respiratory system was normally pressurized without damage, and we confirmed that the developed system was able to evaluate the elasticity of the lung tissue in the rat by using the pressure value obtained at the quasi-static conditions in the case of the ventilation in the animal experiments.

A table-shaped tactile sensor for detecting triaxial force on the basis of strain distribution.

A slim and flexible tactile sensor applicable to the interaction of human and intelligent robots is presented. In particular, a simple sensing principle for decoupling of three-dimensional force is proposed. Sensitivity of the proposed tactile sensor is tested experimentally. To improve the sensitivity of the sensor, a table-shaped sensing element was designed. Table-shaped structure can convert an external acting force into concentrated internal stress. A "triaxial force decoupling algorithm" was developed by combining two-dimensional mapping data calculated by finite element analysis. The sensor was calibrated under normal and tangential forces. The external loads applied to the sensor could be decoupled independently as a function of the strain-gauge responses.

Sensitivity Enhancement of Tube-Integrated MEMS Flow Sensor Using Flexible Copper on Polyimide Substrate.

A tube-integrated flow sensor is proposed in this study by integrating a micro-electro mechanical systems (MEMS) flow-sensing element and electrical wiring structure on the same copper on polyimide (COP) substrate. The substrate was rolled into a circular tube with the flow-sensing element installed at the center of the tube. The signal lines were simultaneously formed and connected to the Cu layer of the substrate during the fabrication of the sensing structure, thus simplifying the electrical connection process. Finally, by rolling the fabricated sensor substrate, the flow sensor device itself was transformed into a circular tube structure, which defined the airflow region. By implementing several slits on the substrate, the sensing element was successfully placed at the center of the tube where the flow velocity is maximum. Compared to the conventional sensor structure in which the sensor was placed on the inner wall surface of the tube, the sensitivity of the sensor was doubled.

Assembly of skeletal muscle cells on a Si-MEMS device and their generative force measurement.

We have fabricated a simple Si-MEMS device consisting of a microcantilever and a base to measure active tension generated by skeletal muscle myotubes derived from murine myoblast cell line C2C12. We have developed a fabrication process for integration of myotubes onto the device. To position myotubes over the gap between the cantilever and the base without damage due to mechanical peeling or the use of an enzymatic reaction, we cultured myotubes on poly-N-isopropylacrylamide (PNIPAAm) as a sacrifice layer. By means of immune staining of alpha-actinin, it was confirmed that a myotube micropatterned onto the device bridged the gap between the cantilever and the base. After 7d differentiation, the myotube was actuated by electrical stimulation. The active tension generated by the myotube was evaluated by measuring the bending of the cantilever using image processing. On twitch stimulation, the myotube on the device contracted and generated active tension in response to the electrical signals. On tetanus tension measurement, approximately 1.0 microN per single myotube was obtained. The device developed here can be used in wide area of in vitro skeletal muscle studies, such as drug screening, physiology, regenerative medicine, etc.

Cell culture arrays using magnetic force-based cell patterning for dynamic single cell analysis.

In order to understand the behavior of individual cells, single cell analyses have attracted attention since most cell-based assays provide data with values averaged across a large number of cells. Techniques for the manipulation and analysis of single cells are crucial for understanding the behavior of individual cells. In the present study, we have developed single cell culture arrays using magnetic force and a pin holder, which enables the allocation of the magnetically labeled cells on arrays, and have analyzed their dynamics. The pin holder was made from magnetic soft iron and contained more than 6000 pillars on its surface. The pin holder was placed on a magnet to concentrate the magnetic flux density above the pillars. NIH/3T3 fibroblasts that were labeled with magnetite cationic liposomes (MCLs) were seeded into a culture dish, and the dish was placed over the pin holder with the magnet. The magnetically labeled cells were guided on the surface where the pillars were positioned and allocated on the arrays with a high resolution. Single-cell patterning was achieved by adjusting the number of cells seeded, and the target cell was collected by a micromanipulator after removing the pin holder with the magnet. Furthermore, change in the morphology of magnetically patterned cells was analyzed by microscopic observation, and cell spreading on the array was observed with time duration. Magnetic force-based cell patterning on cell culture arrays would be a suitable technique for the analysis of cell behavior in studies of cell-cell variation and cell-cell interactions.

Droplet-based gene expression analysis using a device with magnetic force-based-droplet-handling system.

A droplet-based cell lysis and reverse transcription-polymerase chain reaction (PCR) were performed on-chip employing magnetic force-based-droplet-handling system. The actuation with a magnet offers a simple system for droplet manipulation; it does not need mechanical fluidic systems such as pumps and valves for handling solutions. It can be used as a powerful tool for various biochemical applications by moving and coalescing sample droplets using magnetic beads immersed in mineral oil. The droplet containing magnetic beads and the cells were manipulated with the magnet located underneath the channel, and coalesced with a droplet of lysis buffer. Using K562 cells as the leukemia model, the cell lysis, cDNA synthesis, and amplification of WT1 gene that is known as the prognostic factor for acute leukemia were successfully performed from a single cell.