1
Micro/Nanostructured Materials from Droplet Microfluidics

Xin Zhao1, Jieshou Li1, and Yuanjin Zhao1,2

1Medical School of Nanjing University, Research Institute of General Surgery, Jinling Hospital, No. 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, P. R. China

2Southeast University, State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, No. 2, Sipailou, Xuanwu District, Nanjing, 210096, P. R. China

1.1 Introduction

Since the emergence of microfluidics at the beginning of 1980s, microfluidic technologies have been extensively applied in the fabrication of materials with specific physicochemical features and versatile applications [1-3]. This relatively new field is the synergy of science and technology of systems with integrated channels on the microscale dimensions, through which small quantities of fluids (usually 10-9 to 10-18?l) can flow in designed configurations and are precisely controlled and manipulated [4-6]. In the field of microfluidics, as fluid dimensions shrink to the microscale level, their specific surface area increases, thus showing behaviors divergent from those of macroscopic fluids, which can be characterized by three major phenomena: highly efficient mass-heat transfer, relative dominance of viscous force over inertial force, and significant surface effects [7,8]. In addition, the high integration of microfluidic channels facilitates the coexistence and diverse interactions of multiple fluid phases and paves the way for miniaturized systematic control over individual fluids and fluid interfaces [9,10]. These features offer obvious advantages over bulk synthesis, most notably in their ability to ensure monodispersity and control the structure of final products [11-13]. Therefore, microfluidics has promoted the development of multidisciplinary research in physical, chemical, biological, medical, and engineering fields.

Droplet microfluidics is an important subcategory of the microfluidic technologies, which generates and manipulates discrete droplets through immiscible multiphase flows inside the microchannels [14-16]. In the past two decades, fostered by great progress in both theoretical and technical aspects, droplet microfluidics has fulfilled original expectations and become a significant approach to generate materials for a broad range of applications [17-19]. The basic principles and microfluidic devices for droplet generation are shown in Figure 1.1, including a T-junction chip (Figure 1.1a), a flow-focusing chip (Figure 1.1b), and a coaxial structured chip (Figure 1.1c) [20]. In the T-junction chip, the dispersed phase flows from a vertical channel to a horizontal channel filled with the continuous phase. Under the combined action of both shear force and extrusion pressure from the continuous phase, monodispersed droplets are generated. In the flow-focusing chip, the dispersed phase flows from the middle channel and undergoes extrusion force of the continuous phase from all directions. The dispersed phase experiences stretching and breakage, leading to droplet formation. In the coaxial structured chip, the dispersed phase channel is embedded in the continuous phase channel, and the dispersed phase flows parallel to the continuous phase toward the same direction. Also, the dispersed phase is broken into droplets. In microfluidic systems, droplet generation is influenced by microchannel construction, viscosity and flow velocity of each phase, and interfacial tension between adjacent flows. Therefore, the dimensions and production rates of droplets can be regulated by adjusting the above parameters. In addition, through a flexible design of microchannels, double or even multiple emulsions could be generated in a controlled manner (Figure 1.1d,e) [21,22]. These microfluidic droplets have diverse morphologies and components and can serve as excellent templates to synthesize materials with specific structures and functions.

With the development of microfabrication technology, considerable research has been made to synthesize microstructured materials (MMs)/nanostructured materials (NMs) because the microscopic architectures give additional properties to the materials [23-26]. Conventional bulk methods usually adopt a certain physical or chemical procedure (e.g. mechanical stirring) [27,28]. These methods usually generate materials with a monotonous morphology, and the dispersity of products and synthetic processes are difficult to control [29,30]. In particular, for fabrication of composite materials, such as "intelligent materials" or "core-shell materials," the conventional approaches are insufficient to meet the requirements. MMs/NMs synthesized from droplet microfluidics possess narrow size distribution, flexible structures, and desired properties [31-33]. Compared to conventional methods, the advantages of microfluidic synthesis lie in the following aspects [20,34-36]. The material size, structure, and composition are easily controlled, resulting in superior properties and functions. The addition of reagents is very simple, which is beneficial for the manipulation of multistep and multireagent synthesis. Through scale integration of microfluidic systems and equipment automation, the complex reaction process can be largely simplified. Because majority of materials used to make microfluidic chip are facilitated to be observed, real-time monitoring of the reaction process could be realized, which helps to clarify the synthesis mechanism. Therefore, the application of droplet microfluidics to design and prepare MMs/NMs has become a hot topic recently and will bring about infinite possibilities for the future development of materials science.

In this chapter, we summarize the classical and recent achievements in the MMs/NMs engineered from droplet microfluidics and their various applications. We first provide an overview of MMs fabricated by droplet microfluidics, including the droplet formation mechanism and various microchips used to generate different droplets, the methods to prepare MMs templated from these droplets, and the unique and complex structures enabled by microfluidic techniques. We then present basic synthesis methods for inorganic and organic NMs through droplet microfluidics, and the heterogeneous and multifunctional nanostructures from microfluidic platforms are also introduced. Following these two sections, much emphasis will be laid on the applications of the generated MMs/NMs, including drug delivery, cell encapsulation, TE, and analytical applications. Finally, we will discuss the current status and existing challenges and provide opinions on the directions of future development of droplet microfluidics in the synthesis of advanced MMs/NMs.

Figure 1.1 (a-c) The principles and chip designs with different flow regimes for droplet generation, including T-junction (a), flow-focusing (b), and coaxial (c) structured chip. (d) Generation of multiple emulsions in a stepwise flow-focusing device: (i-v) single-, double-, triple-, quadruple-, and quintuple-emulsion droplets, respectively. (e) Generation of multiple emulsions in a stepwise coflow platform.

Source: Ma et al. 2017 [20]. https://www.mdpi.com/2072-666X/8/8/255. Licensed under CCBY 4.0

Source: Adapted with permission from Abate and Weitz [21]. Copyright 2009, John Wiley & Sons.

Source: Adapted with permission from Chu et al. [22]. Copyright 2007, John Wiley & Sons.

1.2 MMs from Droplet Microfluidics

Although the history of MMs with sizes ranging from 1 to 1000?µm has started in the 1960s, their application was only expanded recently after they were utilized as drug delivery agents by mimicking genetic materials carrying pollens [37-39]. Thereafter, other studies have continuously investigated the functionalities of MMs and they are now being utilized in various fields including pharmaceuticals, food industry, cosmetics, photonics, coatings, and printing [40,41]. These applications of MMs depend on their properties that correlate with their size, structure, composition, and configuration [42,43]. Typically, MMs have been prepared through traditional methods including emulsion polymerization, dispersion polymerization, and spray drying [44]. These methods always result in MMs with large polydispersity, poor reproducibility, limited functionality, and less tunable morphology [44-46]. Therefore, it is becoming increasingly urgent to fabricate MMs with defined sizes, morphologies, and compartments in a controlled manner to improve their capability. Droplet microfluidics can generate emulsion droplets with a precisely controlled size, shape, and composition, which provide excellent templates for the synthesis of functional MMs with uniform size, controllable shape, and versatile compositions [47-49]. Moreover, precise control over single emulsion droplets by microfluidics allows further creation of multiple emulsions with highly controllable, nested, and droplet-in-droplet structures [50,51]. Thus, using such multiple...