Shuichi Shoji

Fluids for Sensor Systems

Several techniques for miniaturization of simple chemical and medical analysis systems are described. Miniaturization of total analysis systems realizes a small sample volume, a fast response and reduction of reagents. These features are useful in chemical and medical analysis. During the last decade many micro flow control devices, as well as the micro chemical sensors fabricated by three dimensional microfabrication technologies based on photofabrication, termed micromachining, have been developed. Miniaturized total analysis systems (μTAS) have been studied and some prototypes developed. In microfabricated systems, “microfluidics”, which represent the behavior of fluids in small sized channels, are considered and are very important in the design of micro elements used in μTAS. In this chapter microfluidics applied flow devices, micro flow control devices of active and passive microvalves, mechanical and non-mechanical micropumps and micro flow sensors fabricated by micromachining are reviewed.

A very low-power consumption wireless ECG monitoring system using body as a signal transmission medium

A very low-power consumption wireless system for monitoring ECG (electrocardiogram) is proposed. It consists of an ECG detector/transmitter located on the chest and the relay transmitter placed at the wrist. Between the detector part and the relay transmitter, the signal is send as the AC micro current flows through the tissue of the body. Since this method achieves very low-power signal transmission of about 8 /spl mu/W (400 mV/sub RMS//spl times/20 /spl mu/A/sub RMS/), the system can be driven by a very small power source like a thin film battery. A similar wireless transmission method can be applied for other medical signal/data sensing micro systems sharing the same relay transmitter.

An all SU-8 microfluidic chip with built-in 3D fine microstructures

This paper describes the fabrication method of an all SU-8 microfluidic device with built-in 3D fine micromesh structures. 3D micromesh structures were seamlessly integrated into the SU-8 sealed microchannel. To eliminate gap formation and filling of the microchannel, the built-in micromeshes in the microchannel were formed by photolithography after bonding the SU-8 top-cover layer and the SU-8 bottom substrate. The lift-off method, using lift-off resist as a sacrificial layer, was utilized to release the all SU-8 microfluidic chips. Monolithic SU-8 structures realize uniform physical and chemical surface properties required in microfluidic devices for practical use. As an application, fragmentation of a water droplet in an organic carrier formed by a two-phase flow was demonstrated.

Studies on SiO2-SiO2 bonding with hydrofluoric acid. Room temperature and low stress bonding technique for MEMS

Abstract Studies on SiO 2 –SiO 2 bonding with hydrofluoric acid (HF) are described. This method has a remarkable feature that bonding can be obtained at room temperature. Advantages of this method are low thermal damage, low residual stress and simplicity of the bonding process, which are expected for the packaging and assembly of micro-electro-mechanical systems (MEMS). The bond characteristics were measured under different bonding conditions of HF concentration, applied pressure, another chemicals for bonding and so on. The bond strength depends on the applied pressure during bonding. To achieve reliable bonding, HF concentration of higher than 0.5 wt.% and a large applied pressure of 1.3 MPa are required. The bonding is also observed using KOH solution in stead of HF. Transmission electron microscopy (TEM), secondary ion mass spectrometry (SIMS), radioactive isotope (RI) analysis and electron probe micro analysis (EPMA) were applied to evaluate the bonded interface. The results of these analysis indicated that an interlayer of a silicon oxide complex including hydrogen and fluorine atoms is formed between bonded SiO 2 to SiO 2 . The thickness of the interlayer depends strongly on the applied pressure during bonding. Large bond strength is obtained when the interlayer is thin. The bonding mechanism is expected when the SiO 2 at both surfaces is dissolved in HF solution, and that the interlayer, which is a binding layer, is formed between substrates by resolidification of dissolved silicon dioxide. Formation of the interlayer plays very important roles for the characteristics of HF-bonding.

Partly disposable three-way microvalve for a medical micro total analysis system (μTAS)

Abstract In order to realize a practical medical micro total analysis system ( μ TAS), a partly disposable three-way microvalve has been developed. The separate channel structure and pneumatic actuation are employed considering the problems of whole-blood handling. The microvalve has advantages of easy assembly, large on/off flow ratio (about 10 4 ), no bubble problem, low cost due to the partly disposable structure and perfect process matching to microchemical sensors (amperometric sensors or ISFETs).

A novel fabrication of in-channel 3-D micromesh structure using maskless multi-angle exposure and its microfilter application

This paper presents a novel fabrication method of in-channel three-dimensional micromesh structures using the conventional photolithography. The micromesh was realized by exposing UV light from the backside of the SU-8 coated metal-patterned glass substrate for different angles. Numbers of exposure and irradiation angle decided the shape and the size of micromesh. Based on this technique, three different micromesh-inserted microchannel structures were fabricated. For hydrodynamic characterization, their flow resistances were measured. Finally, for the application of micro total analysis system (/spl mu/TAS), the microfilter was fabricated and its filtering property was demonstrated.

Low-temperature anodic bonding using lithium aluminosilicate-β-quartz glass ceramic

Abstract Silicon-to-glass anodic bonding is performed at temperatures below 180 °C using lithium aluminosllicate- β -quartz glass ceramic. High alkaline ion mobility at low temperature, which is required for bonding, and thermal expansion coefficient matching to Si are realized by controlling the composition of the glass ceramic. Bonding is obtained at a lowest temperature of 140 °C. Useful bonding conditions are temperature above 160 °C (applied voltage above 500 V). Since the etch rate of the glass ceramic is five times higher than that of Pyrex glass in HF wet etching and the undercut is very small with a Cr-Au etch mask, three-dimensional structures are easily fabricated. Low-temperature anodic bonding using this type of glass ceramic is useful for the packaging and assembling of MEMS.

Real-time single-cell imaging of protein secretion

Protein secretion, a key intercellular event for transducing cellular signals, is thought to be strictly regulated. However, secretion dynamics at the single-cell level have not yet been clarified because intercellular heterogeneity results in an averaging response from the bulk cell population. To address this issue, we developed a novel assay platform for real-time imaging of protein secretion at single-cell resolution by a sandwich immunoassay monitored by total internal reflection microscopy in sub-nanolitre-sized microwell arrays. Real-time secretion imaging on the platform at 1-min time intervals allowed successful detection of the heterogeneous onset time of nonclassical IL-1β secretion from monocytes after external stimulation. The platform also helped in elucidating the chronological relationship between loss of membrane integrity and IL-1β secretion. The study results indicate that this unique monitoring platform will serve as a new and powerful tool for analysing protein secretion dynamics with simultaneous monitoring of intracellular events by live-cell imaging.

Use of Folded Micromachined Pillar Array Column with Low-Dispersion Turns for Pressure-Driven Liquid Chromatography

In this study, we show for the first time that the separation efficiency of a pillar array column under pressure-driven liquid chromatography (LC) conditions can be improved using a separation channel with low-dispersion turns. The pillar array column was fabricated by reactive ion etching of a silicon substrate. With the low-dispersion-turn geometry, a column with a length and width of 110 mm and 400 microm, respectively, could be fabricated on a 20 x 20 mm microchip. Under nonretained conditions, the solute bands obtained for fluorescent compounds remained almost unchanged even after passing through the low-dispersion turns; however, significant skewing of the solute bands was observed in the case of constant-radius turns. Two coumarin dyes were well resolved under reversed-phase conditions, and a maximum theoretical plate number of 8000 was obtained. Successful separation of the fluorescent derivatives of six amino acids was achieved in 140 s. These results indicated that the separation efficiency of microchip chromatography could be significantly improved using a long separation channel with low-dispersion turns.

Droplet-based microfluidics for high-throughput screening of a metagenomic library for isolation of microbial enzymes

This paper proposes a high-throughput, function-based screening approach of a metagenomic library for isolating novel microbial enzymes by droplet-based microfluidics. We used gel microdroplets (GMDs) dispersed in oil as picoliter-volume reaction vessels for lipolytic enzyme by encapsulating cells in individual GMDs. Using this approach, we monitored the growth of individual cells encapsulated in GMDs and assessed the enzyme reaction activities at the level of an individual GMD. We then applied this method to screen lipolytic enzyme genes from the metagenomic library constructed from soil collected from a quercus serrate forest of Mount Tsukuba, Ibaraki, Japan. In the workflow presented in this study, metagenomic library clones were encapsulated in 100-pL GMDs with a fluorogenic reporter substrate. A total of 67,000 metagenomic library clones can be screened in only 24 h with reduced consumption of reagents (i.e., <10 μL). As a result, we identified a novel lipolytic enzyme, EstT1, belonging to the EstD2 family of esterases and containing a putative signal peptide, which facilitates enzyme export and catalyzation of substrates in the periplasm. Our study demonstrates the potential of microfluidic GMDs as an efficient tool for metagenomic library screening of industrially relevant enzymes with the potential of significantly reducing the cost and time factors involved in successful practical application of microbial enzymes.