A new design and construction methodology for integration of complicated chemical processing on a microchip was proposed. This methodology, continuous-flow chemical processing (CFCP), is based on a combination of microunit operations (MUOs) and a multiphase flow network. Chemical operations in microchannels, such as mixing, reaction, and extraction, were classified into several MUOs. The complete procedure for Co(II) wet analysis, including a chelating reaction, solvent extraction, and purification was decomposed into MUOs and reconstructed as CFCP on a microchip. Chemical reaction and molecular transport were realized in and between continuous liquid flows in a multiphase flow network, such as aqueous/aqueous, aqueous/organic, and aqueous/organic/aqueous flows. When the determination of Co(II) in an admixture of Cu(II) was carried out using this methodology, the determination limit (2sigma) was obtained as 18 nM, and the absolute amount of Co chelates detected was 0.13 zmol, that is, 78 chelates. The sample analysis time was faster than that of a conventional processing system. Moreover, troublesome operations such as phase separation and acid and alkali washing, all necessary for the conventional system, were simplified. The CFCP methodology proposed here can be applied to various on-chip applications.

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18 cm. As an example of a multilayer flow application, we demonstrated the liquid/liquid extraction of Codimethylaminophenol complex in a microchannel. The solvent-extraction process of the complex into m-xylene in the multilayer flow was found to reach equilibrium in 4 s, while it took 60 s in a simple two-phase extraction.

We developed a novel laser microscope based on the thermal lens effect induced by a coaxial beam comprised of excitation and probe beams. The signal generation mechanism was confirmed to be an authentic thermal lens effect from the measurement of signal and phase dependences on optical configurations between the sample and the probe beam focus, and therefore, the thermal lens effect theory could be applied. Two-point spatial resolution was determined by the spot size of the excitation beam, not by the thermal diffusion length. Sensitivity was quite high, and the detection ability, evaluated using a submicron microparticle containing dye molecules, was 0.8 zmol/µm 2 , hence a distribution image of trace chemical species could be obtained quantitatively. In addition, analytes are not restricted to fluorescent species, therefore, the thermal lens microscope is a promising analytical microscope. A two-dimensional image of a histamine molecule distribution, which was produced in mast cells at the femtomole level in a human nasal mucous polyp, was obtained.

We demonstrated a liquid/liquid and a gas/liquid two-phase crossing flow in glass microchips. A 250-microm-wide microchannel for aqueous-phase flow was fabricated on a top glass plate. Then, as a way to utilize the surface energy difference for stable phase confluence and separation, a 250-microm-wide microchannel for organic-phase (or gas-phase) flow was fabricated on a bottom glass plate and the wall was chemically modified by octadecylsilane (ODS) group. The top and bottom plates were sealed only by pressure. A microchannel pattern was designed so that the two phases made contact at the crossing point of the straight microchannels. The crossing point was observed with an optical microscope. Results showed that the ODS modification of the microchannel wall clearly improved stability of the interface between the two fluids. Pressure difference between fluids was measured and the interface of water and nitrobenzene was stable for the pressure difference from +300 Pa to -200 Pa. The pressure drop in a countercurrent flow configuration was also estimated, and the pressure difference required to realize the counter current flow was less than the allowable pressure range. Finally, we discussed the advantages of utilizing this approach.

An integrated multireactor system for 2 x 2 parallel organic synthesis has been developed on a single glass microchip. Three-dimensional channel circuits in the chip were fabricated by laminating three glass plate layers. The fabrication method is a straightforward extension of the conventional one, and topological equivalence for any three-dimensional circuits can be constructed easily with it. 2 x 2 phase-transfer amide formation reactions, which constitute a simple model for combinatorial synthesis, were successfully carried out on the microchip, and the integrity of the three-dimensional circuits was confirmed. Combinatorial chemistry with multi-microreactors, in conjunction with a high-throughput screening method based on micro-TAS technologies, is expected to provide an efficient tool for drug discovery.

Here we report a design and synthesis of a chemically functional polymer membrane by an interfacial polycondensation reaction and multilayer flow inside a microchannel. Single and parallel dual-membrane structures are successfully prepared by using organic/aqueous two-layer flow and organic/aqueous/organic three-layer flow inside the microchannel followed by an interfacial polycondensation reaction. By using the inner-channel membrane, permeation of ammonia species through the inner-channel membrane is successfully achieved. Furthermore, horseradish peroxidase is immobilized on one side of the membrane surface to integrate the chemical transform function onto the inner-channel membrane. Here substrate permeation through the membrane and subsequent chemical transformation at the membrane surface are realized. The polymer membrane prepared inside the microchannel has an important role in ensuring stable contact of different phases such as gas/liquid or liquid/ liquid and the permeation of chemical species through the membrane. Furthermore, membrane surface modification chemistry allows chemical transformation of permeated chemical species. These methods are expected to lead to development of complicated and sophisticated chemical systems involving membrane permeation and chemical reactions.

A stable three-layer flow system, water/organic solvent/water, has been successfully applied for the first time in a microchannel to get rapid transport through an organic liquid membrane. In the continuous laminar flow region, the analyte (methyl red) was rapidly extracted across the microchannel from the donor to the acceptor phase through the organic solvent phase (cyclohexane). Thermal lens microscopy was used to monitor the process. The thickness of the organic phase, sandwiched by the two aqueous phases, was approximately 64 microm, and it was considered as a thin liquid organic membrane. Permeability studies showed the effects of molecular diffusion, layer thickness, and organic solvent-water partition coefficient on the molecular transport. In the microchip, complete equilibration was achieved in several seconds, in contrast to a conventionally used apparatus, where it takes tens of minutes. The thickness of the organic and aqueous boundary layers was defined as equal to the microchannel dimensions, and the organic solvent-water partition coefficient was determined on a microchip using the liquid/liquid extraction system. Experimental data on molecular transport across the organic membrane were in agreement with the calculated permeability based on the three-compartment water/organic solvent/water model. This kind of experiment can be performed only in a microspace, and the system can be considered as a potential biological membrane for future in vitro study of drug transport.