Hideaki Hisamoto

Microchip-based chemical and biochemical analysis systems

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.

Glass microchip with three-dimensional microchannel network for 2 × 2 parallel synthesis

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.

Fast and high conversion phase-transfer synthesis exploiting the liquid–liquid interface formed in a microchannel chip

The large specific interfacial areas and short molecular diffusion distances provided by glass microchips play important roles not only for effective phase-transfer synthetic reaction, but also for avoiding an undesirable side reaction.

Phase-transfer alkylation reactions using microreactors

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.

Micro wet analysis system using multi-phase laminar flows in three-dimensional microchannel network

A three-dimensional microchannel network with two-level crossings of channels was constructed in a glass microchip by sandwiching an insulating glass plate between two glass plates with microchannels followed by thermal bonding. Pressure-driven stable multi-phase laminar flows inside the three-dimensional channel network were realized by balancing flow rates of syringe pumps. Micro unit operations for mixing, reaction, solvent extraction, and detection were properly arranged in the multi-phase laminar flows, so that four parallel analyses, comprising twenty unit operations in total, could be integrated onto a single chip. Two chelating reagents and two sample solutions containing heavy metal ions (Fe(ii) or Co(ii)) were mixed and reacted in four different combinations using the three-dimensional channel network. After chelating reactions were completed, post processing (solvent extraction or addition of acid) was applied to each solution stream to remove the interferences of coexisting metal ions. Finally, target metal complexes were detected using a thermal lens microscope (TLM). Integrity of the micro system was confirmed by qualitative analysis of Fe(ii) and Co(ii). This is the first example of continuous flow chemical processing utilizing multi-phase laminar flow realized in a three-dimensional channel network.

DISTRIBUTION OF METHYL RED ON THE WATER–ORGANIC LIQUID INTERFACE IN A MICROCHANNEL

Molecular transport across a water–organic liquid interface formed parallel to the side wall of a microchannel on microchips has been studied using methyl red as model compound and cyclohexane and n-octanol as organic solvents. The molecular transport was monitored by thermal lens microscopy and the kinetics of the process was studied for different concentrations and flow velocities. The influence of physico–chemical interactions between the model compound and organicso lvents on liquid–liquid interface was demonstrated in the microspace and corresponding partition coefficients were calculated which confirmed the experimental results.

Healthcare Chip Based on Integrated Electrochemical Sensors Used for Clinical Diagnostics of Bun

Research based on health marker sensors, such as Na+, glucose, K+ have been carried out using integrated ISE (ion selectivity electrode). In this study, focus has been placed on potentiometric measurement of ammonia and blood urea nitrogen (BUN) sensors using new 19-membered crown ionophore, TD19C6 (2,6,13,16,23,26-hexaoxaheptacyclo-[25.4.4.4 7,12.4 17,22.O 1,17.O 7,12.O 17.22]), poly(vinyl chloride) (PVC) membranes along with anionic additives, potassium tetrakis(4-chlorophenyl)borate (k-TCPB), sodium tetrakis(4-fluorophenyl)borate dehydrate (TFPB), and plasticizers, bis(1-butylphenyl)adipate (BBPA) and tris(2-ethylhexyl)trimellitate (TOTM). Screen-printed electrodes Ag/AgCl (250 mm in diameter) and a disposable polycarbonate chip (PC) designed using a trace amount of whole blood are also used.

Capillary-assembled microchip as an on-line deproteinization device for capillary electrophoresis

AbstractA capillary-assembled microchip (CAs-CHIP), prepared by simply embedding square capillaries in a lattice polydimethylsiloxane (PDMS) channel plate with the same channel dimensions as the outer dimensions of the square capillaries, has been used as a diffusion-based pretreatment attachment in capillary electrophoresis (CE). Because the CAs-CHIPs employ square-section channels, diffusion-based separation of small molecules from sample solutions containing proteins is possible by using the multilayer flow formed in the square section channel. When a solution containing high-molecular-weight and low-molecular-weight species makes contact with a buffer solution, the low-molecular-weight species, which have larger diffusion coefficients than the high-molecular-weight species, can be collected in a buffer-solution phase. The collected solution containing the low-molecular-weight species is introduced into the separation capillary to be analyzed by CE. This type of system can be used for CE analysis in which pretreatment is required to remove proteins. In this work a fluorescently labeled protein and rhodamine-based molecules were chosen as model species and a feasibility study was performed.

Fabrication of a Glass Microchip with a Three-Dimensional Channel Network and its Application to a Single-Chip Combinatorial Synthetic Reactor

With two-level crossing structures constructed by utilizing three layers of glass plates, a three-dimensional channel network that makes micro combinatorial synthesis possible was successfully integrated on a single glass microchip.

Micro integrated chemical systems for general use

Publisher Summary This chapter provides information on micro and nano-fabrication technologies that have been introduced into chemical and biotechnologies. It also explains molecular and energy transport between multiphase laminar flow in a micro channel. As for chemical synthesis, micro reactors with sub-millimeter-sized micro channels are now eagerly investigated. Though there are some examples of electrokinetically-driven flow control in micro reactors, pressure-driven flow control is more commonly used for micro reactors. The aim is to develop methodology to integrate as many chemical processes as possible on microchips and to make full use of characteristics of micro space. Therefore, pressure-driven flow and developed techniques to operate chemical processing in pressure-driven laminar flow in micro channels are selected and for this microchips made of glass are used. Glass vessels are commonly used in many chemical experiments because of their chemical inertness and optical transparency. In order to realize these micro chemical systems based on multiphase laminar flow, some stabilization techniques for the multiphase flow has been inevitable. A micro channel with guide structures and surface modification to stabilize multiphase flows has been used. The chapter also presents a micro integration methodology, continuous flow chemical processing (CFCP), based on spontaneous motion of molecules in multi-phase laminar flow network in micro channel circuits.