Simple Method for On-Demand Droplet Trapping in a Microfluidic Device Based on the Concept of Hydrodynamic Resistance.

We demonstrate an innovative method to catch the desired droplets from a train of droplets and immobilize them in traps located in an integrated microfluidic device. To this end, water-in-oil droplets are generated in a flow-focusing junction and then guided to a channel connected to chambers designated for on-demand droplet trapping. Each chamber is connected to a side channel through a batch of microposts. The side channels are also connected to the flexible poly(vinyl chloride) tubes, which can be closed by attaching binder clips. The hydrodynamic resistance of the routes in the device can be changed by opening and closing the binder clips. In this way, droplets are easily guided into individual traps based on the user's demand. A set of numerical simulations was also conducted to investigate the authenticity of the employed idea and to find the optimal geometry for implementing our strategy. This simple method can be easily employed for on-demand droplet trapping without using on-chip valves or complex off-chip actuators proposed in previous studies.

Evaluating the reliability of tumour spheroid-on-chip models for replicating intratumoural drug delivery: considering the role of microfluidic parameters.

Several tumour spheroid-on-chip models have already been proposed in the literature to conduct high throughput drug screening assays. The microfluidic configurations in these models generally depend on the strategies adopted for spheroid formation and entrapment. However, it is not clear how successful they are to mimic in vivo transport mechanisms. In this study, drug transport in different tumour spheroid-on-chip models is numerically investigated under static and dynamic conditions using porous media theory. Moreover, the treatment of a solid tumour at the initial stage of development is modelled using bolus injection and continuous infusion methods. Then, the results of tumour spheroid-on-chip, including drug concentration, cell viability, as well as pressure and fluid shear stress distributions, are compared with those of the solid tumour, assuming identical transport properties in all models. Finally, a new configuration of the microfluidic device along with the optimal drug concentrations is proposed, which can well imitate a given in vivo situation.

Droplet-based microfluidics in biomedical applications.

Droplet-based microfluidic systems have been employed to manipulate discrete fluid volumes with immiscible phases. Creating the fluid droplets at microscale has led to a paradigm shift in mixing, sorting, encapsulation, sensing, and designing high throughput devices for biomedical applications. Droplet microfluidics has opened many opportunities in microparticle synthesis, molecular detection, diagnostics, drug delivery, and cell biology. In the present review, we first introduce standard methods for droplet generation (i.e. passive and active methods) and discuss the latest examples of emulsification and particle synthesis approaches enabled by microfluidic platforms. Then, the applications of droplet-based microfluidics in different biomedical applications are detailed. Finally, a general overview of the latest trends along with the perspectives and future potentials in the field are provided.

Cancer cell enrichment on a centrifugal microfluidic platform using hydrodynamic and magnetophoretic techniques.

Isolation of rare cancer cells is one of the important and valuable stages of cancer research. Regarding the rarity of cancer cells in blood samples, it is important to invent an efficient separation device for cell enrichment. In this study, two centrifugal microfluidic devices were designed and fabricated for the isolation of rare cancer cells. The first design (passive plan) employs a contraction-expansion array (CEA) microchannel which is connected to a bifurcation region. This device is able to isolate the target cells through inertial effects and bifurcation law. The second design (hybrid plan) also utilizes a CEA microchannel, but instead of using the bifurcation region, it is reinforced by a stack of two permanent magnets to capture the magnetically labeled target cells at the end of the microchannel. These designs were optimized by numerical simulations and tested experimentally for isolation of MCF-7 human breast cancer cells from the population of mouse fibroblast L929 cells. In order to use the hybrid design, magnetite nanoparticles were attached to the MCF-7 cells through specific Ep-CAM antibodies, and two permanent magnets of 0.34 T were utilized at the downstream of the CEA microchannel. These devices were tested at different disk rotational speeds and it was found that the passive design can isolate MCF-7 cells with a recovery rate of 76% for the rotational speed of 2100 rpm while its hybrid counterpart is able to separate the target cells with a recovery rate of 85% for the rotational speed of 1200 rpm. Although the hybrid design of separator has a better separation efficiency and higher purity, the passive one has no need for a time-consuming process of cell labeling, occupies less space on the disk, and does not impose additional costs and complexity.

Investigation of a Novel Microfluidic Device for Label-Free Ferrohydrodynamic Cell Separation on a Rotating Disk.

Negative magnetophoresis is a novel and attractive method for continuous microparticle sorting inside a magnetic medium. In this method, diamagnetic particles are sorted based on their sizes using magnetic buoyancy force and without any labeling process. Although this method provides some attractive features, such as low-cost fabrication and ease of operation, there are some obstacles that adversely affect its performance, especially for biological applications. Most types of magnetic media, such as ferrofluids, are not biocompatible, and the time-consuming process of sample preparation can be threatening to the viability of the cells within the sample. Furthermore, in this method, both the target and non-target particles are affected by the magnetic field, and therefore, a high separation efficiency cannot be achieved. In this paper, to isolate the abnormal cells from the other blood cells, a microfluidic device was designed using numerical simulation. This model utilizes negative magnetophoresis on a rotating disk, and to reduce the exposure time of the cells inside the magnetic medium, a micromixer is embedded in the upstream of the separator which rapidly prepares the sample. In this part, diluted blood sample and ferrofluid are mixed together utilizing magnetic force. Afterward, the separator sorts the cells into multiple outlets using magnetic buoyancy force as well as centrifugal force. The numerical procedure employed in this study shows that the proposed model is able to recover ∼100% of the abnormal cells from a particular outlet for binary and ternary separation of the cells with high throughputs. Although this percentage of separation may be lower in reality, the optimization of the proposed design by the numerical method can avoid trial-and-error during costly and time-consuming experiments. Also, the device proposed in this study reduces the exposure time of the cells inside the ferrofluid to just a few seconds, which can improve cell viability.