Search

Abstract To enable the accurate reproduction of organs in vitro, and improve drug screening efficiency and regenerative medicine research, it is necessary to assemble cells with single‐cell resolution to form cell clusters. However, a method to assemble such forms has not been developed. In this study, a platform for on‐site cell assembly at the single‐cell level using optically driven microtools in a microfluidic device is developed. The microtool was fabricated by SU‐8 photolithography, and antibodies were immobilised on its surface. The cells were captured by the microtool through the bindings between the antibodies on the microtool and the antigens on the cell membrane. Transmembrane proteins, CD51/61 and CD44 that facilitate cell adhesion, commonly found on the surface of cancer cells were targeted. The microtool containing antibodies for CD51/61 and CD44 proteins was manipulated using optical tweezers to capture HeLa cells placed on a microfluidic device. A comparison of the adhesion rates of different surface treatments showed the superiority of the antibody‐immobilised microtool. The assembly of multiple cells into a cluster by repeating the cell capture process is further demonstrated. The geometry and surface function of the microtool can be modified according to the cell assembly requirements. The platform can be used in regenerative medicine and drug screening to produce cell clusters that closely resemble tissues and organs in vivo.

Abstract We developed optically driven microtools for processing single biomolecules using a microfluidic workbench composed of a microfluidic platform that functions under an optical microscope. The optically driven microtools have enzymes immobilized on their surfaces, which catalyze chemical reactions for molecular processing in a confined space. Optical manipulation of the microtools enables them to be integrated with a microfluidic device for controlling the position, orientation, shape of the target sample. Here, we describe the immobilization of enzymes on the surface of microtools, the microfluidics workbench, including its microtool storage and sample positioning functions, and the use of this system for on-site cutting of single chromosomal DNA molecules. We fabricated microtools by UV lithography with SU-8 and selected ozone treatments for immobilizing enzymes. The microfluidic workbench has tool-stock chambers for tool storage and micropillars to trap and extend single chromosomal DNA molecules. The DNA cutting enzymes DNaseI and DNaseII were immobilized on microtools that were manipulated using optical tweezers. The DNaseI tool shows reliable cutting for on-site processing. This pinpoint processing provides an approach for analyzing chromosomal DNA at the single-molecule level. The flexibility of the microtool design allows for processing of various samples, including biomolecules and single cells.

A microfluidic probe (MFP) does not require physical walls for flow channels, enabling application of a chemical solution in an open space by injecting and aspirating the solution. However, in conventional MFP fabrication methods, the use of a 2D aperture array at narrow intervals to enhance the function of treatment remains limited. In this study, we developed a stainless MFP (stMFP) to produce a 2D aperture array at narrow intervals. The stMFP was developed using a stacking technique in which stainless steel substrates fabricated by photolithography and a wet etching process were stacked and bonded through thermal diffusion. This process resulted in a 6-row and 8-column aperture array with an aperture size of 100 × 150 µm and a narrow interval of 50 µm. The surface treatment area was evaluated by biopatterning of a fluorescent antibody. The results showed that the stMFP biopatterned a minimum treatment area of 3.3 × 103 µm2, which could be controlled between 5.1 × 104 µm2 and 3.0 × 105 µm2 by changing the aperture arrangement. In addition, when two types of fluorescent antibodies were alternately injected in the row direction, six independent treatment areas of 6.1 × 104 µm2 were formed over a wide area of 3.8 × 105 µm2. Furthermore, biopatterning using a 4 × 4 aperture array showed that a 2D treatment area with 4-rows and 2-columns can be produced with an area of 4.5 × 105 µm2. A single stMFP can form various 2D treatment patterns, which is expected to realize high-performance bioprocessing in the field of biology.

In this study, we focused on direct and quantitative monitoring of sap dynamics in plant stems, and proposed the microscale xylem sap flow sensor. This sensor facilitates the simultaneous measurement of flow velocity and direction by combining the principles of a Granier sensor and a thermal flow sensor. We fabricated micro-sensor chips for functional verification by using MEMS technology, and assembled them on a resin film to facilitate mounting on the epidermis of plants. Furthermore, we measured the sap dynamics by using an experimental setup, and succeeded in measuring the flow velocity and direction at the same time.

In this paper, we propose a simple plasma-less fabrication and integration method for biomicrodevice applications. For optogenetics, microlenses and pinholes irradiating local sight of biological tissue with focused visible light and electrodes measuring a biological electropotential are integrated by using organic materials such as polymer. The proposed fabrication method consists of photolithography and wet-etching process only. The shape of fabricated microlenses measured by a white light interferometer was the diameter of 111.5 μm, the depth of 45.5 μm, and the focal length 320 μm. The impedance of Platinum black electroplated on the fabricated electrode pads was reduced to 200 kΩ. As the results, it is succeeded to integrate electrode pads, microlenses and pinholes without plasma etching process. The fabricated dish is assembled with a light irradiation device having two LEDs. By the light irradiation test, the fabricated dish is expected to be utilized in a variety of neuroscience researches. By the test for cytotoxicity, it is succeeded to create neural network on the fabricated dish.

A novel gas-sealed capacitive pressure sensor with a temperature compensation structure is reported. The pressure sensor is sealed by Au-Au diffusion bonding under a nitrogen ambient with a pressure of 100 kPa and integrated with a platinum resistor-based temperature sensor for human activity monitoring applications. The capacitance-pressure and capacitance-temperature characteristics of the gas-sealed capacitive pressure sensor without temperature compensation structure are calculated. It is found by simulation that a ring-shaped structure on the diaphragm of the pressure sensor can mechanically suppress the thermal expansion effect of the sealed gas in the cavity. Pressure sensors without/with temperature compensation structures are fabricated and measured. Through measured results, it is verified that the calculation model is accurate. Using the compensation structures with a 900 μm inner radius, the measured temperature coefficient is much reduced as compared to that of the pressure sensor without compensation. The sensitivities of the pressure sensor before and after compensation are almost the same in the pressure range from 80 kPa to 100 kPa.

An olfactory display is necessary for effective multimodal information communication. The relatively large size of current olfactory displays does not support integration with other information devices. Thus, in this study, a heat-driven-type microelectromechanical system (MEMS) olfactory display that is only a few square centimeters in size and, thus, suitable for integration, is proposed. The olfactory display was fabricated by implementing a microfabrication process, and the fundamental driving conditions for the heater and valve were confirmed. Furthermore, a perfume diffusion experiment was conducted to characterize the olfactory display. The diffusion of the perfume was successfully synchronized with the open/close time of the valve.

This paper presents the integration of an inductor by complementary metal-oxide-semiconductor (CMOS) compatible processes for integrated smart microsensorsystems that have been developed to monitor the motion and vital signs of humans invarious environments. Integration of radio frequency transmitter (RF) technology withcomplementary metal-oxide-semiconductor/micro electro mechanical systems (CMOS/MEMS) microsensors is required to realize the wireless smart microsensors system. Theessential RF components such as a voltage controlled RF-CMOS oscillator (VCO), spiralinductors for an LC resonator and an integrated antenna have been fabricated and evaluatedexperimentally. The fabricated RF transmitter and integrated antenna were packaged withsubminiature series A (SMA) connectors, respectively. For the impedance (50 ) matching,a bonding wire type inductor was developed. In this paper, the design and fabrication of thebonding wire inductor for impedance matching is described. Integrated techniques for theRF transmitter by CMOS compatible processes have been successfully developed. Aftermatching by inserting the bonding wire inductor between the on-chip integrated antennaand the VCO output, the measured emission power at distance of 5 m from RF transmitterwas -37 dBm (0.2 μW).