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 developed microfluidic-based pure chitosan microfibers (approximately 1 meter long, 70-150 microm diameter) for liver tissue engineering applications. Despite the potential of the chitosan for creating bio-artificial liver chips, its major limitation is the inability to fabricate pure chitosan-based microstructures with controlled shapes because of the mechanical weakness of the pure chitosan. Previous studies have shown that chitosan micro/nanofibers can be fabricated by using chemicals and electrospinning techniques. However, there is no paper regarding pure chitosan-based microfibers in a microfluidic device. This paper suggests a unique method to fabricate pure chitosan microfibers without any chemical additive. We also analyzed the chemical, mechanical, and diffusion properties of pure chitosan microfibers. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectrometry and electron spectroscopy for chemical analysis (ESCA) were used to analyze the chemical composition of the synthesized chitosan microfibers. We measured the mechanical axial-force and diffusion coefficient in pure chitosan-based microfibers using fluorescence recovery after photobleaching (FRAP) techniques. Furthermore, to evaluate the capability of the microfibers for liver tissue formation, hepatoma HepG2 cells were seeded onto the chitosan microfibers. The functionality of these hepatic cells cultured on chitosan microfibers was analyzed by measuring albumin secretion and urea synthesis. Therefore, this pure chitosan-based microfiber chip could be a potentially useful method for liver tissue engineering applications.

In this paper, we present that trapping and dissipating of bubbles in a microfluidic cell culture system can be simultaneously achieved by utilizing curved geometry principles. For this end, a simple and cost-effective method to fabricate a curved hemispherical microfluidic channel is presented. On the basis of an analytical model, the mechanism that the hemispherical well can trap various sizes of bubbles better than the cylindrical well is described, and we present a quantitative comparison of the trapping capabilities of the hemispherical versus conventional cylindrical wells through experiments. The surface tension is another important factor to trap bubbles, which was also verified through the analysis and experiments. In the hemispherical wells, the trapped bubbles were spontaneously dissipated under the flowing condition without using any active source, and we characterized the degassing process by measuring the area of bubbles occupied in the well over time. For an application to a biomedical system, a cell culture chamber was combined with the bubble trapping system, and the performance of the system was verified by culturing HeLa cells with the flowing bubbled culture media. Conclusively, the suggested method demonstrated excellent performance in trapping of microbubbles and dissipation without using any peripheral device, and will be broadly applied in biomedical microfluidic research.

A tunable process for polydimethylsiloxane (PDMS) nanoslit fabrication is developed for nanofluidic applications. A microcontact printing (μCP) of a laterally spreading self-assembled hexadecanethiol (HDT) layer, combined with in situ curing of a sliding SU-8 droplet, enables precise and independent tuning of a nanoslit-mold width and height using a single μCP master mold. The SU-8 nanoslit-mold is replicated using a hard-soft composite PDMS to prevent channel collapse at low (<0.2) aspect ratio (height over width). The fluidic characteristics as well as dimensions of nanoslits fabricated with various conditions are analyzed using a fluorescein sample and AFM images. Finally, concentration polarization-based sample preconcentration is successfully demonstrated at the nanoslit boundary where an electric double-layer is overlapped.

In this paper, we analyzed the behavior of moving structures in a check valve micropumping system and proposed a method to improve the freedom of motion of such structures. A model ball valve in a microchannel system was designed for this study. The behavior of the glass sphere, which acted as an independent flow check valve in the PDMS microfluidic channel, was analyzed. We found that the motion of the ball valve in the microchannel was sensitive to the properties of the interface between the ball, channel, and liquid. The glass ball valve moved freely when methanol or ethanol was introduced into the PDMS channel. However, the ball valve adhered to the PDMS channel when deionized (DI) water or cell culture media was introduced. Such behavior inhibits the applicability of this micropump to biological systems. The adhesion properties were modeled using the theory of interfacial actions between heterogeneous materials. The theoretical model successfully predicted the interaction properties that governed ball valve motion in the PDMS microchannels. To ameliorate the excessive adhesion in DI water or cell culture media, a hybrid inorganic/organic polymer (HR4) was used to coat the PDMS channel. In the HR4-coated ball valve micropump, the glass ball moved freely in DI water and cell culture media. Finally, the biocompatibility of the HR4 coating was evaluated by pumping human mesenchymal stem cells (hMSCs) suspended in media, and the pumped cells were cultured and evaluated for viability. A good viability demonstrated that the HR4 pump was biocompatible.

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