3.1. Microdroplets encapsulation

The development of emulsification via microfluidic in the past decades is embodied in various fields. In the aspect of system design and fabrication, continuous reports with regards to new material development coupled with creative, novel fabrication techniques, enable evolutional microfluidic system from conventional two-dimensional (2D) straight microchannel to multifunctional three-dimensional (3D) systems [51]. In the aspect of theory and applications, in-depth understanding of the flow dynamic as mentioned in the previous section leads to much unique systems design for generation and manipulation of droplets with diverse behaviors and surface morphologies in various applications being reported [52–54]. Although the encapsulation process may seem straightforward, there are few considerations need to be noted. One common technique used is the addition of surface active agent to either continuous or dispersed phase. Such addition can create distinctive microdroplets formation, but not always an ideal solution to the development of more complex microfluidic systems with

multi-inputs. Various innovative proposals have been attempted to resolve this issue, both for passive and active emulsion encapsulation system. An active encapsulation involves usage of external forces such as electricity to encapsulate emulsion, which is not favorable when it is deployed in biology-related application. While passive emulsion encapsulation method more often carries low throughput as its main shortcoming, the simplicity in encapsulation mechanism makes it a popular choice for microdroplet encapsulation.

Despite of these latest advances, the relevant techniques to manipulate droplet fission by constriction are commonly performed in a 2D single planar microchannel. For instance, Rosenfeld et al. investigated splitting and deformations of a large number of drops in a concentrated emulsion when it flows through a narrow constriction in 2D monolayer Poly (dimethylsiloxane) (PDMS) microchannel [59]. There is no design employing 3D bilayer microchannel consisting of constriction formed by bifurcated junction. Bifurcated junction work should be focused because the flow of emulsions through porous media is important in many industrial processes, while the porous media normally have small constrictions with bifurcated junction [65]. For example, natural porous media such as oil reservoir features with complex interior structure formed by a number of constrictions or pores with heterogeneity of physiochemical characteristics. Industrial processes such as mobility control in enhanced oil recovery requires prediction of the evolution of the microstructure of the injected fluids in microstructure and their bulk rheological properties. However, there is still a lack of complete understanding towards the stability and break-up of individual emulsions as they flow through simple constrictions or pores, especially when the interactions among the emulsions are important. Moreover, in some biomedical applications such as drug delivery, the encapsulated drugs must go through media with complex 3D constrictions, such as blood capillaries or the porous material of a tissue structure in the human body. These constrictions normally feature with bifurcated junction. In some cases, these constrictions are the locations for drug release, thus the emulsion droplets must burst to release its contents. In other cases, the emulsion droplets must be transported through the constrictions to reach the targeted release locations, thus breakup must not occur in the constrictions. Therefore, it demands a thorough understanding of the physics of emulsion flow through constrictions to predict and manipu-

Microdroplets Advancement in Newtonian and Non-Newtonian Microfluidic Multiphase System

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late the release of active ingredients from such emulsions (Figure 4).

Figure 4. Droplet splitting in a microfluidic device. (A) 2D splitting: (i) droplets split repeatedly through Y-shaped junctions; (ii, iii) scheme illustration and microscopic image of droplet splitting mediated by a square obstruction. (B) 3D splitting: (i) scheme of the splitting process; (ii vi) microscopic images showing droplets entering the junction and split into two daughter droplets. Reproduced with permission from [51]. Copyright 2017 American Chemistry Society.

There have been much microdroplet encapsulation attempts done in both Newtonian and non-Newtonian fluids system. In recent years, focus on microdroplets encapsulation had been given to non-Newtonian fluids especially in the medical field and in drug synthesis and released related work. In the case of non-Newtonian fluid systems, an integrated comprehensive droplet digital detection (IC 3D) was used to encapsulate bacteria such as E.coli in the blood content for detection purpose [55]. The device is able to encapsulate bacterial into microdroplets that will allow real time disease detection with high result accuracy. Such approach has shorten the conventional detection method that requires longer time. Much of other developments on microdroplet encapsulation can be found in various literatures.

### 3.2. Microdroplets fission

Generally, microdroplet splitting can be divided into two main approaches, i.e. active fission and passive fission, while the latter one is more widely accepted due to advantages including ease of implementation and low cost. Passive fission mainly depends on the fluid flow resistance and geometries in respective channels of the microfluidic system. A variety of geometries have been demonstrated in passive fission where microdroplet is split as it flows past Tjunction [56], arbitrary angle [57], obstacle [58] or through a narrow constriction [59]. It was found that the microdroplet fission occurs at bifurcation if length of the droplet in the microchannel is greater than the circumference on the edge of the microdroplet. The microdroplet splits evenly if the resistances of the two daughter channels have the same fluidic resistance downstream of the bifurcation. Since fluidic resistance is proportional to microchannel length, changing the length of one of the two daughter channels allows microdroplets to split unevenly. In this way, the volume ratio of the daughter droplets produced by the fission can be changed. A large post can be employed near the middle of a microchannel to induce microdroplet fission, the ratio of sizes of daughter droplets can be changed by adjusting the position of the post in the microchannel [60]. A repeating bifurcation structure can be used to split a single parent droplet into 8 or 16 daughter droplets of nanoliter volumes. Droplet breakup occurs because of a high surface tension pressure relative to the pressure drop in the microchannel [61]. Multiple monodisperse droplets can be generated using a side-branch structure with varied resistance in the microchannel; the size of the daughter droplets was controlled by the size of the original liquid plugs, thus providing a wide tuning range of droplet size [62]. A hydrophobic valve was used to arrest the flow of fluid into each daughter channel, while placed a waste channel at downstream of the daughter channels to drain excess fluid. The series of daughter channels can split a single liquid sample plug into multiple smaller plugs effectively [63]. This technology can allow for simultaneous screening for multiple viruses [64].

Despite of these latest advances, the relevant techniques to manipulate droplet fission by constriction are commonly performed in a 2D single planar microchannel. For instance, Rosenfeld et al. investigated splitting and deformations of a large number of drops in a concentrated emulsion when it flows through a narrow constriction in 2D monolayer Poly (dimethylsiloxane) (PDMS) microchannel [59]. There is no design employing 3D bilayer microchannel consisting of constriction formed by bifurcated junction. Bifurcated junction work should be focused because the flow of emulsions through porous media is important in many industrial processes, while the porous media normally have small constrictions with bifurcated junction [65]. For example, natural porous media such as oil reservoir features with complex interior structure formed by a number of constrictions or pores with heterogeneity of physiochemical characteristics. Industrial processes such as mobility control in enhanced oil recovery requires prediction of the evolution of the microstructure of the injected fluids in microstructure and their bulk rheological properties. However, there is still a lack of complete understanding towards the stability and break-up of individual emulsions as they flow through simple constrictions or pores, especially when the interactions among the emulsions are important. Moreover, in some biomedical applications such as drug delivery, the encapsulated drugs must go through media with complex 3D constrictions, such as blood capillaries or the porous material of a tissue structure in the human body. These constrictions normally feature with bifurcated junction. In some cases, these constrictions are the locations for drug release, thus the emulsion droplets must burst to release its contents. In other cases, the emulsion droplets must be transported through the constrictions to reach the targeted release locations, thus breakup must not occur in the constrictions. Therefore, it demands a thorough understanding of the physics of emulsion flow through constrictions to predict and manipulate the release of active ingredients from such emulsions (Figure 4).

multi-inputs. Various innovative proposals have been attempted to resolve this issue, both for passive and active emulsion encapsulation system. An active encapsulation involves usage of external forces such as electricity to encapsulate emulsion, which is not favorable when it is deployed in biology-related application. While passive emulsion encapsulation method more often carries low throughput as its main shortcoming, the simplicity in encapsulation mecha-

There have been much microdroplet encapsulation attempts done in both Newtonian and non-Newtonian fluids system. In recent years, focus on microdroplets encapsulation had been given to non-Newtonian fluids especially in the medical field and in drug synthesis and released related work. In the case of non-Newtonian fluid systems, an integrated comprehensive droplet digital detection (IC 3D) was used to encapsulate bacteria such as E.coli in the blood content for detection purpose [55]. The device is able to encapsulate bacterial into microdroplets that will allow real time disease detection with high result accuracy. Such approach has shorten the conventional detection method that requires longer time. Much of other developments on

Generally, microdroplet splitting can be divided into two main approaches, i.e. active fission and passive fission, while the latter one is more widely accepted due to advantages including ease of implementation and low cost. Passive fission mainly depends on the fluid flow resistance and geometries in respective channels of the microfluidic system. A variety of geometries have been demonstrated in passive fission where microdroplet is split as it flows past Tjunction [56], arbitrary angle [57], obstacle [58] or through a narrow constriction [59]. It was found that the microdroplet fission occurs at bifurcation if length of the droplet in the microchannel is greater than the circumference on the edge of the microdroplet. The microdroplet splits evenly if the resistances of the two daughter channels have the same fluidic resistance downstream of the bifurcation. Since fluidic resistance is proportional to microchannel length, changing the length of one of the two daughter channels allows microdroplets to split unevenly. In this way, the volume ratio of the daughter droplets produced by the fission can be changed. A large post can be employed near the middle of a microchannel to induce microdroplet fission, the ratio of sizes of daughter droplets can be changed by adjusting the position of the post in the microchannel [60]. A repeating bifurcation structure can be used to split a single parent droplet into 8 or 16 daughter droplets of nanoliter volumes. Droplet breakup occurs because of a high surface tension pressure relative to the pressure drop in the microchannel [61]. Multiple monodisperse droplets can be generated using a side-branch structure with varied resistance in the microchannel; the size of the daughter droplets was controlled by the size of the original liquid plugs, thus providing a wide tuning range of droplet size [62]. A hydrophobic valve was used to arrest the flow of fluid into each daughter channel, while placed a waste channel at downstream of the daughter channels to drain excess fluid. The series of daughter channels can split a single liquid sample plug into multiple smaller plugs effectively [63]. This technology can allow for simultaneous screening for multi-

nism makes it a popular choice for microdroplet encapsulation.

microdroplet encapsulation can be found in various literatures.

3.2. Microdroplets fission

152 Microfluidics and Nanofluidics

ple viruses [64].

Figure 4. Droplet splitting in a microfluidic device. (A) 2D splitting: (i) droplets split repeatedly through Y-shaped junctions; (ii, iii) scheme illustration and microscopic image of droplet splitting mediated by a square obstruction. (B) 3D splitting: (i) scheme of the splitting process; (ii vi) microscopic images showing droplets entering the junction and split into two daughter droplets. Reproduced with permission from [51]. Copyright 2017 American Chemistry Society.
