Core-Shell Particles: From Fabrication Methods to Diverse Manipulation Techniques.

Core-shell particles are micro- or nanoparticles with solid, liquid, or gas cores encapsulated by protective solid shells. The unique composition of core and shell materials imparts smart properties on the particles. Core-shell particles are gaining increasing attention as tuneable and versatile carriers for pharmaceutical and biomedical applications including targeted drug delivery, controlled drug release, and biosensing. This review provides an overview of fabrication methods for core-shell particles followed by a brief discussion of their application and a detailed analysis of their manipulation including assembly, sorting, and triggered release. We compile current methodologies employed for manipulation of core-shell particles and demonstrate how existing methods of assembly and sorting micro/nanospheres can be adopted or modified for core-shell particles. Various triggered release approaches for diagnostics and drug delivery are also discussed in detail.

Fabrication and characterization of core-shell microparticles containing an aqueous core.

Core-shell microparticles containing an aqueous core have demonstrated their value for microencapsulation and drug delivery systems. The most important step in generating these uniquely structured microparticles is the formation of droplets and double emulsion. The droplet generator must meet the performance and reliability requirements, including accurate size control with tunability and monodispersity. Herein, we present a facile technique to generate surfactant-free core-shell droplets with an aqueous core in a microfluidic device. We demonstrate that the geometry of the core-shell droplets can be precisely adjusted by the flow rates of the droplet components. As the shell is polymerized after the formation of the core-shell droplets, the resulting solid microparticles ensure the encapsulation of the aqueous core and prevent undesired release. We then study experimentally and theoretically the behaviour of resultant microparticles under heating and compression. The microparticles demonstrate excellent stability under both thermal and mechanical loads. We show that the rupture force can be quantitatively predicted from the shell thickness relative to the outer shell radius. Experimental results and theoretical predictions confirm that the rupture force scales directly with the shell thickness.

Realization of Three-Dimensionally MEMS Stacked Comb Structures for Microactuators Using Low-Temperature Multi-Wafer Bonding with Self-Alignment Techniques in CMOS-Compatible Processes.

A high-aspect-ratio three-dimensionally (3D) stacked comb structure for micromirror application is demonstrated by wafer bonding technology in CMOS-compatible processes in this work. A vertically stacked comb structure is designed to circumvent any misalignment issues that could arise from multiple wafer bonding. These out-of-plane comb drives are used for the bias actuation to achieve a larger tilt angle for micromirrors. The high-aspect-ratio mechanical structure is realized by the deep reactive ion etching of silicon, and the notching effect in silicon-on-insulator (SOI) wafers is minimized. The low-temperature bonding of two patterned wafers is achieved with fusion bonding, and a high bond strength up to 2.5 J/m2 is obtained, which sustains subsequent processing steps. Furthermore, the dependency of resonant frequency on device dimensions is studied systematically, which provides useful guidelines for future design and application. A finalized device fabricated here was also tested to have a resonant frequency of 17.57 kHz and a tilt angle of 70° under an AC bias voltage of 2 V.

Acoustic Biosensors and Microfluidic Devices in the Decennium: Principles and Applications.

Lab-on-a-chip (LOC) technology has gained primary attention in the past decade, where label-free biosensors and microfluidic actuation platforms are integrated to realize such LOC devices. Among the multitude of technologies that enables the successful integration of these two features, the piezoelectric acoustic wave method is best suited for handling biological samples due to biocompatibility, label-free and non-invasive properties. In this review paper, we present a study on the use of acoustic waves generated by piezoelectric materials in the area of label-free biosensors and microfluidic actuation towards the realization of LOC and POC devices. The categorization of acoustic wave technology into the bulk acoustic wave and surface acoustic wave has been considered with the inclusion of biological sample sensing and manipulation applications. This paper presents an approach with a comprehensive study on the fundamental operating principles of acoustic waves in biosensing and microfluidic actuation, acoustic wave modes suitable for sensing and actuation, piezoelectric materials used for acoustic wave generation, fabrication methods, and challenges in the use of acoustic wave modes in biosensing. Recent developments in the past decade, in various sensing potentialities of acoustic waves in a myriad of applications, including sensing of proteins, disease biomarkers, DNA, pathogenic microorganisms, acoustofluidic manipulation, and the sorting of biological samples such as cells, have been given primary focus. An insight into the future perspectives of real-time, label-free, and portable LOC devices utilizing acoustic waves is also presented. The developments in the field of thin-film piezoelectric materials, with the possibility of integrating sensing and actuation on a single platform utilizing the reversible property of smart piezoelectric materials, provide a step forward in the realization of monolithic integrated LOC and POC devices. Finally, the present paper highlights the key benefits and challenges in terms of commercialization, in the field of acoustic wave-based biosensors and actuation platforms.

Development of a Microfluidic Droplet-Based Microbioreactor for Microbial Cultivation.

Droplet microfluidics creates new opportunities for microbial engineering. Most microbial cultivations are carried out in bioreactors, which are usually bulky and consume a large amount of reagents and media. In this paper, we propose a microfluidic droplet-based microbioreactor for microbial cultivation. A microfluidic device was designed and fabricated to produce many droplet-based microbioreactors integrated with an AC electric field for the manipulation of these microbioreactors. Droplets encapsulating fluorescent Escherichia coli cells were generated, sorted, and trapped individually in small chambers. Fluorescence intensity was monitored to determine cell growth. An electric field with varying voltages and frequencies manipulates the droplets, simulating an oscillation effect. Initial results showed that electric field does not affect cell growth. A comparison with shake flask showed that a similar standard growth curve is obtained when cultivating at room temperature. This device has the potential for making droplet-based microbioreactors an alternative for microbial engineering research.

On-Demand Droplet Merging with an AC Electric Field for Multiple-Volume Droplet Generation.

We introduce a unique system to achieve on-demand droplet merging and splitting using a perpendicular AC electric field. The working mechanism involves a micropillar to split droplets, followed by electrocoalescence using an AC electric field. Adjusting the parameters of the AC signal and conductivity of the fluid result in different merging regimes. We observed a minimum threshold voltage and a strong influence of the surfactant. We hypothesize that the merging process is caused by dipole-dipole coalescence between the daughter droplets. At the same time, adjustment of the conductivity reveals a shift in the merging regimes and can be explained with an electric circuit diagram. Size-based sorting using this merging phenomenon is subsequently demonstrated, where alternate, single, double, and triple droplets sorting were achieved. The concept presented in this paper is potentially useful for drug dispensing or multivolume digital polymerase chain reaction, as droplets of multiple sizes can be generated simultaneously.

Influence of Interfacial Gas Enrichment on Controlled Coalescence of Oil Droplets in Water in Microfluidics.

Interfacial gas enrichment (IGE) of dissolved gases in water is shown to govern the strong attraction between solid hydrophobic surfaces of an atomic force microscopy (AFM) colloidal probe and solid substrate. However, the role of IGE in controlling the attraction between fluid-fluid interfaces of foam films and emulsion films is difficult to establish by AFM techniques because of the extremely fast coalescence. Here, we applied droplet-based microfluidics to capture the fast coalescence event under the creeping flow condition and quantify the effect of IGE on the drainage and stability of water films between coalescing oil droplets. The amount of dissolved gases is controlled by partially degassing the oil phase. When the amount of dissolved gases (oxygen) in oil decreases (from 7.89 to 4.59 mg/L), the average drainage time of coalescence significantly increases (from 19 to 50 ms). Our theoretical quantification of the coalescence by incorporating IGE into the multilayer van der Waals attraction theory confirms the acceleration of film drainage dynamics by the van der Waals attractive force generated by IGE. The thickness of the IGE layer decreases from 5.5 to 4.9 nm when the amount of dissolved gas decreases from 7.89 to 4.59 mg/L. All these results establish the universal role of dissolved gases in governing the strong attraction between particulate hydrophobic interfaces.

Fundamentals of Differential Particle Inertial Focusing in Symmetric Sinusoidal Microchannels.

Focusing and separation of particles such as cells at high throughput is extremely attractive for biomedical applications. Particle manipulation based on inertial effects requires a high flow speed and thus is well-suited to high-throughput applications. Recently, inertial focusing and separation using curvilinear microchannels has been attracting a great amount of interest because of the linear structure for parallelization, small device footprint, superior particle-focusing performance, and easy implementation of particle separation. However, the curvature directions of these microchannels alternate, leading to variations in both the magnitude and direction of the induced secondary flow. Accumulation of this variation along the channel causes unpredictable behaviors of particles. This paper systematically investigates the inertial-focusing phenomenon in low-aspect-ratio symmetric sinusoidal channels. First, we comprehensively studied the effects of parameters such as viscosity, flow conditions, particle size, and geometric dimensions of the microchannel on differential particle focusing. We found that particle inertial focusing is generally independent of fluid kinematic viscosity but highly dependent on particle size, flow conditions, and channel dimensions. Next, we derived an explicit scaling factor and included all four dimensionless parameters (particle-blockage ratio, curvature ratio, Dean number, and channel aspect ratio) in a single operational map to illustrate the particle-focusing patterns. Finally, we proposed a rational guideline to intuitively instruct the design of channel dimensions for separation of a given particle mixture.

Negative Pressure Induced Droplet Generation in a Microfluidic Flow-Focusing Device.

We introduce an effective method to actively induce droplet generation using negative pressure. Droplets can be generated on demand using a series of periodic negative pressure pulses. Fluidic network models were developed using the analogy to electric networks to relate the pressure conditions for different flow regimes. Experimental results show that the droplet volume is correlated to the pressure ratio with a power law of 1.3. Using a pulsed negative pressure at the outlet, we are able to produce droplets in demand and with a volume proportional to the pulse width.

Self-Aligned Interdigitated Transducers for Acoustofluidics.

The surface acoustic wave (SAW) is effective for the manipulation of fluids and particles at microscale. The current approach of integrating interdigitated transducers (IDTs) for SAW generation into microfluidic channels involves complex and laborious microfabrication steps. These steps often require full access to clean room facilities and hours to align the transducers to the precise location. This work presents an affordable and innovative method for fabricating SAW-based microfluidic devices without the need for clean room facilities and alignment. The IDTs and microfluidic channels are fabricated using the same process and thus are precisely self-aligned in accordance with the device design. With the use of the developed fabrication approach, a few types of different SAW-based microfluidic devices have been fabricated and demonstrated for particle separation and active droplet generation.

Polymeric Biomaterials for Medical Implants and Devices.

In this review article, we focus on the various types of materials used in biomedical implantable devices, including the polymeric materials used as substrates and for the packaging of such devices. Polymeric materials are used because of the ease of fabrication, flexibility, and their biocompatible nature as well as their wide range of mechanical, electrical, chemical, and thermal behaviors when combined with different materials as composites. Biocompatible and biostable polymers are extensively used to package implanted devices, with the main criteria that include gas permeability and water permeability of the packaging polymer to protect the electronic circuit of the device from moisture and ions inside the human body. Polymeric materials must also have considerable tensile strength and should be able to contain the device over the envisioned lifetime of the implant. For substrates, structural properties and, at times, electrical properties would be of greater concern. Section 1 gives an introduction of some medical devices and implants along with the material requirements and properties needed. Different synthetic polymeric materials such as polyvinylidene fluoride, polyethylene, polypropylene, polydimethylsiloxane, parylene, polyamide, polytetrafluoroethylene, poly(methyl methacrylate), polyimide, and polyurethane have been examined, and liquid crystalline polymers and nanocomposites have been evaluated as biomaterials that are suitable for biomedical packaging (section 2). A summary and glimpse of the future trend in this area has also been given (section 3). Materials and information used in this manuscript are adapted from papers published between 2010 and 2015 representing the most updated information available on each material.