The microfluidic devices have drawn great attentions and applied to various research aspects such as micro-scale heat transfer analysis or biomedical engineering. The designs of microfluidic devices and their flow fields are important to the success of the applications for heat exchanger or drug delivery. The designs and flow fields of microfluidic devices can be examined and investigated using numerical method with commercial software; however, experimental approach are necessary to further validate or compare with the numerical data. Conventional experiment approaches utilize micro-machined pressure and temperature sensors, like micro-membrane pressure sensors or micro-thermocouples, to acquire pressure and temperature data. However, the micro-machined sensors have the limitation of numbers of sensor implantation and consequently discrete data.

In the past decade, a new experiment technique has been developed and it has been applied to various microfluidic devices for investigating the flow field. It is adapted from a luminescence-based pressure/temperature measurement technique known as pressure- and temperature-sensitive paint (PSP/TSP). The PSP/TSP sensor is prepared by selecting luminescent molecules and mixing with polymer binders, then coating on a glass slide. The PSP/TSP coated glass slide is used as cover glass to seal microfluidic devices made by PDMS. During the experiment, a UV light is used as excitation light source and the luminescence intensity emitted from luminescent molecules changes the based on the nearby oxygen concentration (as oxygen quenching) or temperature (as thermal quenching). A scientific grade CCD camera is used to collect the luminescence data in images. The luminescence intensity can be further calibrated and translated into pressure and temperature data. Detailed pressure and temperature profiles have been successfully acquired in microfluidic devices [1]. Heat transfer analysis inside the microchannel has been executed after the fluid and surface temperature obtained by TSP measurements. The oxygen and nitrogen gases mixing in a T-type micromixer can also be realized by using PSP sensors [2]. The experimental results obtained by PSP/TSP measurements have been compared with numerical simulation with ANSYS Fluent, and good agreement have been established [3]. In addition, the temperature evolution inside a microfluidic device with a recess microchannel has been recently measured by TSP measurement and it has been used for the design and improvement of the microfluidic device for microorganism cultivation. 

The schematic of PSP/TSP measurement is illustrated in Figure 1. Figure 2 presents the detailed pressure distribution acquired by PSP sensor in a 90-degree bend microchannel with an air flow at Reynolds number of 274. The oxygen concentration profile has been successfully obtained by PSP sensor in a T-type micromixer at the Reynold number of 51.3, as shown in Figure 3. Figure 4 (a), (b), and (c) present the fluid temperature, surface temperature, and the local heat transfer evolution around a 90-degree bend microchannel measured by TSP sensor with liquid flow at Reynolds number is 67.4. Detailed heat transfer evolution has been obtained and higher Nusselt number has identified near the outside wall after the corner, the region where the liquid flow impinging at the wall.

We report an automated microdroplet platform for chemostat culture of bacterial cell, and continuous detection of optical density of microdroplet. The microdroplets, divided by air bubbles, are continuously injected into PMMA micro-fluidic chip using injection pump controlled by PC. Microdroplets are divided or merged via microchannels on the chip. On the top side of michochannels, optical detector is applied to acquire optical density of luminescent light. This platform is used to study chemostat continuous culture Escherichia coli on the chip, while concentration of bacterial cell can be online detected after tracer solution is merged into microdroplet. This system has several key characteristics: small (<100 μL, typically 2 μL) samples of liquids and suspensions of bacteria that are introduced directly into the chip; a sequence of droplets with compositions can controlled by injection speed and time; dividing and merging procedures can be easily programmed by user according experimental requirement; the droplets are detected with an in-line homemade optic spectrophotometer that measures cell growth, which detection limit reach 0.01 in 637nm wavelength. The E. coli detection experiment for water sanitary is on the way, while positive result can be expected.

This paper presents a new optofluidic detection system to measure the absolute refractive index map of host cells.  This new system: cell refractive index tomography, can measure the absolute refractive index map of host cells. During virus infection, cell morphology and the intracellular contents of the host cells are changed. Such changes can be monitored by detecting the refractive index variation. By monitoring of the cell’s refractive index, the detection of virus infection in real-time and label-free is determined.

 In this presentation, we suggested a “diffusio-kinetic ion concentration polarization (diffusio-kinetic ICP)” for a spontaneous ion exchange system. The diffusio-kinetic ICP utilized the mechanisms of an ion diffusion, a spontaneous ion depletion and a spontaneous solute exclusion [1, 2] so that the ion exchange system would be accomplished without any external power source.

 When saline water was introduced into the microchannel of which side walls were composed of cation-selective membrane, the ion exchange process occurred and then the desalted diffuse layer was formed nearby the membrane. Because of the flow of saline water, the desalted diffuse layer would be deformed but retain finite thickness. If we gather the water adjacent to the membrane surface at outlet, we can get the desalted water through the spontaneous manner which means that any external electrical source is not required, whereas the ICP needs the electrically driven ionic flux through the membrane.

 Through the rigorous theoretical analysis, the diffusio-kinetic ICP was characterized by the Sherwood number which is the ratio of convective transfer and diffusion rate. When Sh << 1, the second term the transport phenomenon became the diffusion-dominant mass transport. On the other hand, when Sh >> 1, convective transport was dominant. For each case, the desalted layer would be overlapped depending on Sh as shown in Fig. 2.

 Furthermore, the desalted layer was experimentally visualized in micro/nanofluidic platform. When the desalted layer was developed near the membrane surface, the concentration gradient was generated inside the desalted layer. Under a diffusiophoretic mechanism [3], the charged particles would be excluded from the nanoporous membrane as shown in Fig. 3. Thus, the spontaneous ion depletion was able to be verified by the direct visualization with various cases of Sh. Note that the thickness of the desalted layer was usually larger than the thickness of the particle exclusion zone because of the working mechanism of the diffusiophoresis.

 The fact that the diffusio-kinetic ICP platform can work without any external power source implied the merits in terms of the power consumption and the low-cost operation compared with the conventional technologies so that the diffusio-kinetic ICP would be an effective mean in remote and resource-limited settings.

The paper presents a novel manufacturing process for microlens arrays (MLA). This process used micro machining, double-sided PDMS casting, and plasma bonding to create a hybrid microfluidic chip for manufacturing an MLA on a PDMS substrate. Compared to other reported methods for MLA, this method is rapid, cost-efficient, and capable of manufacturing MLA with various physical dimensions, including sag height and curvature, on a single substrate. The fundamental idea of this method is to deform the PDMS membrane by changing the hydraulic pressure inside the microchannel. Experiment were realized to understand the relationship between the hydraulic pressure inside the microchannel and the deformation of PDMS. And to characterize the uniformity of the MLA, an automatic optical system was built to measure the focal length and curvature of each microlens.

Evaporation of multicomponent droplets has gained much attention nowadays because of their complex flow fields and various deposition patterns. Here we observe strong vortex flows in evaporating sodium chloride (NaCl) saline droplets with suspended alumina oxide (Al₂O₃) nanoparticles. The vortex flows taking place in the saline droplets with nanoparticles is enhanced with the proceeding of evaporation, which is distinctly different from the previously reported case of drying binary mixture droplets with the vortex decaying with time [1,2]. Moreover, such a flow regime occurs neither in the pure water droplet with suspended Al₂O₃ nanoparticles nor in the NaCl salt droplet with fluorescent microspheres. So the vortex flow is speculated to be resulting from the synergic effects of both nanoparticles and the NaCl salt. The objective of our study is to explore the evolution of the vortex flow and its dependence on the salt concentration.

The experiments were carried out in an open condition with the temperature at 22±1℃ and the relative humidity at 55±5%. The experiment setup is shown in Figure 1. Evaporation of the saline nanofluid droplet with 5% NaCl and 0.4 wt. % Al₂O₃ before crystallization from a top view are shown in Figure 2. The evolution of the flow can be roughly divided into two regimes. In Regime I, a Marangoni recirculation loop forms at the center of the droplet as shown in Figure 3. Figure 4 shows the diagram of the vortex flow in the evaporating droplet with 5% NaCl and 0.8 wt. % Al₂O₃ at the early stage of Regime II and the trajectories of particles tracked from the evaporating droplet with 5% NaCl and 0.01 wt. % Al₂O₃. In this regime, the recirculation loop loses its symmetry with its center migrating towards the droplet edge. The recirculation loop then breaks into several small vortex flows at the ultimate stage of evaporation.

The maximum velocity in Regime II of the evaporating droplet with 5% NaCl and 0.01 wt. % Al₂O₃ is obtained based on the particle trajectories with the order of magnitude at 1 mm/s. While the maximum velocity acquired from the analysis of Particle Imaging Velocimetry in the droplet containing 5% NaCl and 0.01 wt. % fluorescent microspheres is at the order of magnitude of 1 µm/s, indicating that the strong vortex do not occur in the saline droplet without nanoparticles. Study on the effect of different salt concentration reveals that with the decrease in the salt concentration, the acceleration of the recirculation loop in Regime I slows down while the droplet tends to generate more small vortex flows at the late evaporation stage before crystallization.

In summary, this study provides an insight into the flow structure in the evaporating saline nanofluid droplet and attempts to explore the effect of salt concentration in driving the flow.

Separation of particles, biological cells and its combination for clinical applications has resulted in an increasing growth of microscale continuous-flow particles and cells manipulation techniques. To design and develop effective techniques, numerical simulation approach is more cost-effective. Numerical simulation can be treated to replicate the condition of physical experiment, as closely as possible, or they can be employed to study what-if scenarios in which can help to identify which factors are most influencing the physical outcomes. Simulation can provide details not available from experiments and taken together, will surely help to resolve the physical processes. In this talk, we will share the methodology and applications of i-MADE: Immersed Boundary Method for Micro-fluidics Advanced Design and Engineering. i-MADE implements a moving-least-square immersed boundary method for solving viscous incompressible flow involving deformable and rigid boundaries on a uniform Cartesian grid. i-MADE handles the fluid motion, the deformable interface motion and the interaction with the immersed rigid boundaries simultaneously in order to account for the complex interaction between the fluid and the immersed boundaries. For rigid objects, no-slip conditions at the rigid boundaries are enforced using the direct-forcing approach which utilizes moving least squares (MLS) method to reconstruct the velocity at the forcing points in the vicinity of the rigid boundaries. For deformable boundaries, MLS method is also employed to construct the interpolation and distribution operators for the immersed boundary points in the vicinity of the rigid boundaries. i-MADE uses the Jacobian-free Newton–Krylov method to advance the location of the elastic boundaries implicitly to greatly improve the time step. The large boundary deformation is taken into account by using a subdivision thin-shell model. i-MADE finds its application particularly useful in biological fluid dynamics or in any other application areas with large boundary deformations and moving boundaries.

Integrated micro chemical systems on a chip, called as microfluidics, have been expected as evolutional tools for high speed, functional and compact instrumentations for analysis, synthesis, bio and related sciences and technologies. Due to the technological development, microfluidic technology is now moving into the practical applications. One of them is collaboration with a hospital in The University of Tokyo for medical diagnosis. We developed a micro-ELISA (enzyme-linked immunosorbent assay) and constructed a practical system. The amount of sample was reduced to one drop of blood, and analysis time became several minutes order. The system is compact and easy to use. The system was applied to real patient samples, and some of the patients were rescued by this sensitive micro-ELISA systems. Currently, as a new research field, the space size is downsizing to 10-100 nm space, which we call extended-nano space. The space provide high functions for analysis due to the small space (smaller than wavelength of visible light). For example, we reported high resolution chromatography, single molecule immunoassay devices. The volume of the extended-nano space is aL to fL, which is several orders smaller than the single cell volume (~pL). The extended-nano space is promising for single cell and single molecule (protein) analysis, which are required in general cell biology and medical research. In this presentation, we introduce the technologies and applications  by micro/extended-nano fluidic devices.

Single cell detection and analysis offers a new dimension to look for disease related mutations within biological samples. Analyzing samples at the single cell level will give unprecedented information and is necessary for the next frontier in precision, targeted medicine. Current detection mechanisms are often limited by population-averaged studies, potentially missing out on specific disease related mutations critical to understanding or diagnosing the disease properly. Here we present a microfluidic biochip that can isolate single cells efficiently. Our device is effective to minimize cell losses that aids in the sample preparation of rare cell events such as circulating tumor cells (CTCs) in peripheral blood. We had demonstrated that our device was useful to allow sensitive detection of critical mutations linked to drug response, which would otherwise be missed out in bulk analysis. In our preliminary clinical study, we revealed that CTC counts within lung cancer patients were limiting and the dominant EGFR mutations such as L858R and T790M were present within these CTCs. It also highlighted the heterogeneous nature of the disease as not all cells carry these mutations. We envision the biochip will enable efficient isolation of rare single cell samples and coupled with downstream molecular characterization of CTCs will aid in realizing the personalized medicine for cancer patients.

Presentation Title: Bacterial Cell Incubation and Detection in Automation Microdroplet System.

We report an automated microdroplet platform for chemostat culture of bacterial cell, and continuous detection of optical density of microdroplet. The microdroplets, divided by air bubbles, are continuously injected into PMMA micro-fluidic chip using injection pump controlled by PC. Microdroplets are divided or merged via microchannels on the chip. On the top side of michochannels, optical detector is applied to acquire optical density of luminescent light. This platform is used to study chemostat continuous culture Escherichia coli on the chip, while concentration of bacterial cell can be online detected after tracer solution is merged into microdroplet. This system has several key characteristics: small (<100 μL, typically 2 μL) samples of liquids and suspensions of bacteria that are introduced directly into the chip; a sequence of droplets with compositions can controlled by injection speed and time; dividing and merging procedures can be easily programmed by user according experimental requirement; the droplets are detected with an in-line homemade optic spectrophotometer that measures cell growth, which detection limit reach 0.01 in 637nm wavelength. The E. coli detection experiment for water sanitary is on the way, while positive result can be expected.