In this study, we developed a tunable sheathless focusing method for focusing micrometer- and nanometer-sized particles, using ion concentration polarization (ICP) in an ion-selective, resin-coated channel. The particle movement was regulated using an electric field, and by varying the flow rate and ionic strength of the liquid solution; various phenomena were observed, depending on the particle properties. Here, we provide insights into the physical basis of the ICP-focusing phenomena, and a statistical approach for analyzing the particle movement. This ICP-focusing technology is an approach that could be applied for the separation and sorting of various particles, including cells, proteins, and bacteria.
This review presents an application of micromixer technologies, which have driven a number of critical research trends over the past few decades, particularly for chemical and biological fields. Micromixer technologies in this review are categorized according to their applications: (1) chemical applications, including chemical synthesis, polymerization, and extraction; (2) biological applications, including DNA analysis, biological screening enzyme assays, protein folding; and (3) detection/analysis of chemical or biochemical content combined with NMR, FTIR, or Raman spectroscopies. In the chemical application, crystallization, extraction, polymerization, and organic synthesis have been reported, not only for laboratory studies, but also for industrial applications. Microscale techniques are used in chemical synthesis to develop microreactors. In clinical medicine and biological studies, microfluidic systems have been widely applied to the identification of biochemical products, diagnosis, drug discovery, and investigation of disease symptoms. The biological and biochemical applications also include enzyme assays, biological screening assays, cell lysis, protein folding, and biological analytical assays. Nondestructive analytical/detection methods have yielded a number of benefits to chemical and biochemical processes. In this chapter, we introduce analytical methods those are frequently integrated into micromixing technologies, such as NMR, FT-IR, and Raman spectroscopies. From the study of micromixers, we discovered that the Re number and mixing time depends on the specific application, and we clustered micromixers in various applications according to the Re number and mixing performance (mixing time). We expect that this clustering will be helpful in designing of micromixers for specific applications.
We present a microfluidic device generating three-dimensional (3D) coaxial flow by the addition of a simple hillock to produce an alginate core-shell microcapsule for the efficient formation of a cell spheroid. A hillock tapered at downstream of the two-dimensional focusing channel enables outside flow to enclose the core flow. The aqueous solution in the core flow was focused and surrounded by 1.8% alginate solution to be solidified as a shell. The double-layered coaxial flow (aqueous phase) was broken up into a droplet by the shear flow of oleic acid (oil phase) containing calcium chloride for the polymerization of the alginate shell. The droplet generated from the laminar coaxial flow maintained a double-layer structure and gelation of the alginate solution made a core-shell microcapsule. The shell-thickness of the microcapsule was adjusted from 8-21 μm by the variation of two aqueous flow rates. The inner shape of the shell was almost spherical when the ratio of the water-glycol mixture in the core flow exceeded 20%. The microcapsule was used to form a spheroid of embryonic carcinoma cells (embryoid body; EB) by injecting a cell suspension into the core flow. The cells inside the microcapsule aggregated into an EB within 2 days and the EB formation rate was more than 80% with strong compaction. The microcapsule formed single spherical EBs without small satellite clusters or a bumpy shape as observed in solid microbeads. The microfluidic chip for encapsulation of cells could generate a number of EBs with high rate of EB formation when compared with the conventional hanging drop method. The core-shell microcapsule generated by 3D focusing in the microchannel was effective in forming large number of spherical cell clusters and the encapsulation of cells in the microcapsule is expected to be useful in the transplantation of islet cells or cancer stem cell enrichment.
Abstract High-aspect ratio micro- and nano-structures have been used for the production of a variety of applications. In this paper, we describe a simple and cost-effective approach to fabricate an arrayed microarchitecture with an ultra-high aspect ratio using soft materials. The shapes and sizes of the honeycomb structure can be easily modulated by changing the dimensions and position of the base mould pattern and the pressure. The honeycomb structure is used to prepare a drug delivery patch and a microwell array to form cell spheroids without cell loss. The honeycomb structures prepared using natural ECM (collagen–Matrigel) materials are successfully fabricated. The hepatocytes and endothelial cells are seeded and co-cultured in the ECM-based micro-honeycomb to prepare a 3D liver model successfully mimicking an ultrastructure of liver and providing enhanced liver function.
This paper presents a novel way of designing a flow focusing channel for microchip flow cytometers. With this method we increased throughput and sensitivity of particle detection at the same time. Generally, to increase the detection throughput of a flow cytometer, the speed of the flow inside the focusing channel needs to be increased, hence reducing the time of exposure to laser beam. With the shorter exposure time, both the fluorescence and scatter signal from the target particles become dimmer. To increase the sensitivity of signal detection, however, the speed of the flow should be decreased so as to decrease throughput of detection. To overcome this dilemmatic problem, we integrated an expansion channel inside a focusing channel. Signals from particles in an expansion channel were about 10 times brighter than those in a normal channel. With this enhanced sensitivity, we could also speed up the inlet flow, which in turn increases the overall throughput of detection.
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