Biomedical subjects
Publications and source records attributed to Hideaki Hisamoto.
Phase-transfer alkylation in a microreactor proceeds smoothly, and the reaction has been found to be more efficient than that in a round-bottomed flask with vigorous stirring; we have observed by an optical microscope study that an interfacial area provided by organic and aqueous phases is more extended in a microreactor.
This review focuses on chemical and biochemical analysis systems using pressure-driven microfluidic devices or microchips. Liquid microspace in a microchip has several characteristic features, for example, short diffusion distances, high specific interfacial area and small heat capacity. These characteristics are the key to controlling micro unit operations and constructing new integrated chemical systems. By combining multiphase laminar flow and the micro unit operations, such as mixing, reaction, extraction and separation, continuous flow chemical processing systems are realized in the microchip format. By applying these concepts, several different analysis systems were successfully integrated on a microchip. In this paper, we introduce the microchip-based chemical systems for wet analysis of cobalt ion, multi-ion sensors, immunoassay, and cellular analysis.
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 thermal lens microscope (TLM) detection of capillary electrophoresis (CE) utilizing microchip technology was developed. Fused-silica capillaries with an inner diameter of 50 microm were directly connected to a microchannel in a microchip. The detection limit by TLM was estimated as 2.8 x 10(-7) absorbance by measuring pure water. The detection limit of derivatized amino acids determined by CE-TLM was estimated as 2.4 x 10(-8) M, which was 100 times lower than that of conventional absorbance detection.
This review focuses on the integration of chemical and biochemical analysis systems into glass microchips for general use. By combining multiphase laminar flow driven by pressure and micro unit operations, such as mixing, reaction, extraction and separation, continuous-flow chemical processing systems can be realized in the microchip format, while the application of electrophoresis-based chip technology is limited. The performances of several analysis systems were greatly improved by microchip integration because of some characteristics of microspace, i.e., a large specific interface area, a short molecular diffusion time, a small heat capacity and so on. By applying these concepts, several different analysis systems, i.e., wet analysis of cobalt ion, multi-ion sensor, immunoassay, and cellular analysis, were successfully integrated on a microchip. These microchip technologies are promising for meeting the future demands of high-throughput chemical processing.
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.
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.
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.