<p>Conventional solution-phase synthesis of azo compounds is complicated by the need for precise pH and temperature control, high concentrations of pH control reagents, and by-product removal. The microdroplet synthesis method has solved these problems.</p>

We developed a microfluidic device that enables selective droplet extraction from multiple droplet-trapping pockets based on dielectrophoresis. The device consists of a main microchannel, five droplet-trapping pockets with side channels, and drive electrode pairs appropriately located around the trapping pockets. Agarose droplets capable of encapsulating biological samples were successfully trapped in the trapping pockets due to the difference in flow resistance between the main and side channels. Target droplets were selectively extracted from the pockets by the dielectrophoretic force generated between the electrodes under an applied voltage of 500 V. During their extraction from the trapping pockets, the droplets and their contents were exposed to an electric field for 400–800 ms. To evaluate whether the applied voltage could potentially damage the biological samples, the growth rates of Escherichia coli cells in the droplets, with and without a voltage applied, were compared. No significant difference in the growth rate was observed. The developed device enables the screening of encapsulated single cells and the selective extraction of target droplets.

We have developed an efficient, stable device for generating single-micrometer-scale (1-2 mu m) droplets based on the fragmentation of droplet tails by tailing. The device, created by a simple soft lithography process, induced continuous droplet fragmentation by branched channels under low-flow conditions (1-10 mu L/min). The flow rate and surfactant concentration were also important factors for droplet fragmentation. Examining 10 combinations of flow rate and surfactant concentration revealed the optimal conditions, which produced droplets less than 2 mu m in size at a generation rate of 61.1%. With this method, we efficiently encapsulated cell-mimicking microbeads into passively generated single-micrometer-scale microdroplets.

We developed a method for passively controlling microdroplet rotation, including interior rotation, using a parallel flow comprising silicone and sesame oils. This device has a simple 2D structure with a straight channel and T-junctions fabricated from polydimethylsiloxane. A microdroplet that forms upstream moves into the sesame oil. Then, the largest flow velocity at the interface of the two oil layers applies a rotational force to the microdroplet. A microdroplet in the lower oil rotates clockwise while that in the upper oil rotates anti-clockwise. The rotational direction was controlled by a simple combination of sesame and silicone oils. Droplet interior flow was visualized by tracking microbeads inside the microdroplets. This study will contribute to the efficient creation of chiral molecules for pharmaceutical and materials development by controlling rotational direction and speed.

For high throughput size controllable micro droplet generation, a three step half and half size/volume division of source droplet device using three stage cascade channel is introduced. Passive and active size/volume ratio controllable source droplet division devises are reported next. Finally, two types of microdroplet (daughter) generation devices using hydrodynamic droplet breakup of source droplet (mother) are described.

Recently, chemical operations with microfluidic devices, especially droplet-based operations, have attracted considerable attention because they can provide an isolated small-volume reaction field. However, analysis of these operations has been limited mostly to aqueous-phase reactions in water droplets due to device material restrictions. In this study, we have successfully demonstrated droplet formation of five common organic solvents frequently used in chemical synthesis by using a simple silicon/glass-based microfluidic device. When an immiscible liquid with surfactant was used as the continuous phase, the organic solvent formed droplets similar to water-in-oil droplets in the device. In contrast to conventional microfluidic devices composed of resins, which are susceptible to swelling in organic solvents, the developed microfluidic device did not undergo swelling owing to the high chemical resistance of the constituent materials. Therefore, the device has potential applications for various chemical reactions involving organic solvents. Furthermore, this droplet generation device enabled control of droplet size by adjusting the liquid flow rate. The droplet generation method proposed in this work will contribute to the study of organic reactions in microdroplets and will be useful for evaluating scaling effects in various chemical reactions.

In this study, microdroplets are regarded as a “small laboratory”, and complex chemical azo compound was firstly synthesis. The synthesis of azo compounds requires accurate pH control. Furthermore, the reaction is accompanied by heat generation. Synthesis applying microdroplets has advantages over temperature control (ice cold→room temperature (23℃)), pH reagent concentration (5.62 molL-1→0.50 molL-1), synthesis time (3,600 sec→4 sec), and recrystallization work was not necessary. The microdroplet rapidly released heat and no side reaction due to heat occurred. The microdroplet method enables accurate pH control and enables highly pure synthesis.

Bacterial persisters are phenotypic variants that survive the treatment of lethal doses of growth-targeting antibiotics without mutations. Although the mechanism underlying persister formation has been studied for decades, how the persister phenotype is switched on and protects itself from antibiotics has been elusive. In this study, we focused on the lactate dehydrogenase gene (ldhA) that was upregulated in an Escherichia coli persister-enriched population. A survival rate assay using an ldhA-overexpressing strain showed that ldhA expression induced persister formation. To identify ldhA-mediated persister formation at the single-cell level, time-lapse microscopy with a microfluidic device was used. Stochastic ldhA expression was found to induce dormancy and tolerance against high-dose ampicillin treatment (500 μg/ml). To better understand the underlying mechanism, we investigated the relationship between ldhA-mediated persister formation and previously reported persister formation through aerobic metabolism repression. As a result, ldhA expression enhanced the proton motive force (PMF) and ATP synthesis. These findings suggest that ldhA-mediated persister formation pathway is different from previously reported persister formation via repression of aerobic metabolism.

This paper presents mechanically reinforced low-concentration alginate fibers by embedding inner cores of high-concentration alginate. 3D structures by stacking multiple polydimethylsiloxane (PDMS) layers allow the microfluidic formation and control of the isolated cores in the continuous flow. The alginate hydrogel fibers are simply spun, and the compartments, central core, surrounding cores, and outer shell layer are successfully verified. The results demonstrate the great potential for the development of complex fibrous materials, particularly for biological applications, which require specific morphology and composition of the fibers.

In this paper, an investigation of a vinylidene fluoride–trifluoroethylene (VDF/TrFE) copolymer film for use in a nonpolarized energy harvester is presented. The Fourier transform infrared spectroscopy and X-ray diffraction analysis of a nonpolarized VDF/TrFE copolymer film indicate that polymer crystallinity depends on film thickness. Furthermore, the growth of the polar structure (β phase) is observed upon the reduction in the thickness. However, power generation does not exhibit a linear behavior because the generation capacity increases with the thickness. These results indicate that the film thickness for a nonpolarized harvester must be optimized to obtain the maximum output.

This paper presents the formation of complex cross-sectional microfibers using three-dimensional microfluidic devices. The compartments and shapes of core and shell layers in the microfibers were independently controlled via three-dimensional fluidic channels fabricated by the combination of sheath units. The number of layers is easily expanded by the stacking of these units. Therefore, the highly heterogeneous microfibers of alginate hydrogel are obtained in polydimethylsiloxane structures. This widely expandable method has great potential for the development of functional and complex fiber-shaped materials.

This study describes the synthesis of an azo-Mn(II) complex requiring an accurate pH control. The reaction conditions for the delicate azo-Mn(II) complex could be precisely controlled using a microfluidic device. The microfluidic method showed the following advantages over the conventional method: the concentration of the pH-control reagent was reduced (1/15), the reaction time was remarkably decreased from 4 h to less than 1 s, and the reaction temperature was lowered from 40 to 23 degrees C. Moreover, the microfluidic device suppressed the oxidation of the compound and did not require cooling to remove the heat of reaction. In addition, the conventional method uses harsh pH control, whereas the microfluidic device permits mild pH control.

A microfluidic stamping method to form functional shapes on a cross section in fiber-shaped flow is proposed. Microfluidic stamping and overstamping allow various cross sectional shapes on the 3D flow. The shapes can be controlled by a change in combination of structures and fluidic conditions which correspond to stamp type and stamping force.

Efficient microfluidic synthesis of chiral salen Mn(II) and Co(II) complexes containing lysozyme was achieved. The reaction conditions for the delicate protein were controlled precisely with a separation barrier in the microfluidic device. The microfluidic method has the following advantages over the conventional method: a remarkable reduction in the reaction time from 4.5 h to less than 1 s for the synthesis of Mn(II) and Co(II) complexes, a reduction in the reaction temperature from 40 to 23 degrees C, and no need for an N-2 atmosphere because all the reagents are isolated from the air. A three-fold yield improvement was achieved for Mn(II) and Co(II) complexes containing lysozyme compared with conventional synthesis.

This research proposed a sheath flow formation method for complex 3D structure such as multi-core and multi-sheath using multi-stacked PDMS units. Cross sectional shape of the flow and the number of sheath layer were defined simply by combination of different PDMS units. The stacked PDMS units allowed independent fluid injection of different layers and the short sheath area realized low diffusion between each layer. Furthermore, the proposed 3D device fabrication method requires only one point alignment. The sheath flow formation method is useful for wide applications which require fiber materials of specific cross sectional shapes and layers.

We conducted an experiment on the fabrication of fluidic devices for producing fine droplets. In our proposed method, multiple channels were fabricated by using a focused ion beam (FIB) system. The minimum feature top width was found to be approximately 56 nm. When both the target width and depth of one channel were set to 500 nm, the resultant top width was 750-780 nm, the bottom width was 250-320 nm, and the depth was 560 nm, almost achieving the target size for the channel depth.