Tiantian Kong

Fabrication and characterization of monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells for controlled drug release.

Monodisperse PLGA-alginate core-shell microspheres with controlled size and homogeneous shells were first fabricated using capillary microfluidic devices for the purpose of controlling drug release kinetics. Sizes of PLGA cores were readily controlled by the geometries of microfluidic devices and the fluid flow rates. PLGA microspheres with sizes ranging from 15 to 50μm were fabricated to investigate the influence of the core size on the release kinetics. Rifampicin was loaded into both monodisperse PLGA microspheres and PLGA-alginate core-shell microspheres as a model drug for the release kinetics studies. The in vitro release of rifampicin showed that the PLGA core of all sizes exhibited sigmoid release patterns, although smaller PLGA cores had a higher release rate and a shorter lag phase. The shell could modulate the drug release kinetics as a buffer layer and a near-zero-order release pattern was observed when the drug release rate of the PLGA core was high enough. The biocompatibility of PLGA-alginate core-shell microspheres was assessed by MTT assay on L929 mouse fibroblasts cell line and no obvious cytotoxicity was found. This technique provides a convenient method to control the drug release kinetics of the PLGA microsphere by delicately controlling the microstructures. The obtained monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells could be a promising device for controlled drug release.

Droplet based microfluidic fabrication of designer microparticles for encapsulation applications

Developing carriers of active ingredients with pre-determined release kinetics is a main challenge in the field of controlled release. In this work, we fabricate designer microparticles as carriers of active ingredients using droplet microfluidics. We show that monodisperse droplet templates do not necessarily produce monodisperse particles. Magnetic stirring, which is often used to enhance the droplet solidification rate, can promote breakup of the resultant microparticles into fragments; with an increase in the stirring time, microparticles become smaller in average size and more irregular in shape. Thus, the droplet solidification conditions affect the size, size distribution and morphology of the fabricated particles, and these attributes of the microparticles strongly influence their release kinetics. The smaller the average size of the microparticles is, the higher the initial release rate is. The release kinetics of drug carriers is strongly related to their characteristics. The understanding of this relationship enables the fabrication of tailor-designed carriers with a specified release rate, and even programmed release to meet the needs of applications that require a complex release profile of the active ingredients.

Microfluidic fabrication of polymeric core-shell microspheres for controlled release applications

We report a facile and robust microfluidic method to fabricate polymeric core-shell microspheres as delivery vehicles for biomedical applications. The characteristics of core-shell microspheres can be precisely and easily tuned by manipulating the microfluidic double emulsion templates. The addition of a shell can significantly improve the versatility as well as functionality of these microspheres as delivery vehicles. We demonstrate that the nature of the shell material plays an important role in the properties of the core-shell delivery vehicles. The release kinetics is significantly influenced by the material of the shell and other characteristics such as the thickness. For example, by adding a poly(lactic-co-glycolic acid) (PLGA) shell to an alginate core, the encapsulation efficiency is enhanced and undesired leakage of hydrophilic actives is prevented. By contrast, adding an alginate shell to PLGA core can lead to a reduction of the initial release rate, thus extending the release period of hydrophobic actives. Microfluidic fabrication enables the generation of precisely controlled core-shell microspheres with a narrow size distribution, which enables the investigation of the relationship between the release kinetics of these microspheres and their characteristics. The approach of using core-shell particles as delivery vehicles creates new opportunities to customize the release kinetics of active ingredients.

Tip-multi-breaking in Capillary Microfluidic Devices

We report tip-multi-breaking (TMB) mode of droplet breakup in capillary microfluidic devices. This new mode appears in a region embraced by Cai = 0 and lg(Cai) = − 8.371(Ca0) −7.36 with Ca0 varying from 0.35 to 0.63 on the Cai – Ca0 phase diagram, Cai and Ca0 being the capillary numbers of inner and outer fluids, respectively. The mode is featured with a periodic, constant-speed thinning of the inner liquid tip and periodic formation of a sequence of droplets. The droplet number n in a sequence is determined by and increases with outer phase capillary number, and varies from two to over ten. The distribution of both pinch-off time and size of the droplets in a sequence is a geometric progression of common ratio that depends exclusively on and increases monotonically with the droplet number from its minimum value of 0.5 at n = 2 to its maximum value of 1 as n tends to infinity. These features can help identify the unique geometric morphology of droplet clusters and make them promising candidates for encryption and anti-fake identification.

Capillary micromechanics for core–shell particles

In this work, we have developed a facile, economical microfluidic approach as well as a simple model description to measure and predict the mechanical properties of composite core-shell microparticles made from materials with dramatically different elastic properties. By forcing the particles through a tapered capillary and analyzing their deformation, the shear and compressive moduli can be measured in one single experiment. We have also formulated theoretical models that accurately capture the moduli of the microparticles in both the elastic and the non-linear deformation regimes. Our results show how the moduli of these core-shell structures depend on the material composition of the core-shell microparticles, as well as on their microstructures. The proposed technique and the understanding enabled by it also provide valuable insights into the mechanical behavior of analogous biomaterials, such as liposomes and cells.

Engineering polymeric composite particles by emulsion-templating: thermodynamics versus kinetics

We investigated the important factors that control the structure of polymeric particles fabricated from emulsion templates. We found that the most energetically stable structure predicted by interfacial energy analysis is not always achieved. The slow dynamics due to an increase in the viscosity of the emulsion phases prevents the polymeric particles from achieving their equilibrium structure. We devised a novel strategy to remove this kinetic barrier, thus achieving the expected equilibrium structure. By considering both the thermodynamic and kinetic aspects during the droplet evolution process, a spectrum of final particle structures can be manipulated in a controlled manner. Our work will enable particle engineering for applications including drug delivery, biomimetic vesicles and photonics.

Liquid metal droplets with high elasticity, mobility and mechanical robustness

Non-stick, ultra-elastic liquid metal droplets were fabricated by coating polytetrafluoroethylene (PTFE) particles onto the surface of NaOH-treated liquid metal droplets. The liquid metal droplets consisted of a liquid metal core, a thin anti-oxidation layer to maintain the high surface tension of the liquid metal and a particle-interpenetrated shell to enhance the mobility of the droplet.

Well-defined porous membranes for robust omniphobic surfaces via microfluidic emulsion templating

Durability is a long-standing challenge in designing liquid-repellent surfaces. A high-performance omniphobic surface must robustly repel liquids, while maintaining mechanical/chemical stability. However, liquid repellency and mechanical durability are generally mutually exclusive properties for many omniphobic surfaces—improving one performance inevitably results in decreased performance in another. Here we report well-defined porous membranes for durable omniphobic surfaces inspired by the springtail cuticle. The omniphobicity is shown via an amphiphilic material micro-textured with re-entrant surface morphology; the mechanical durability arises from the interconnected microstructures. The innovative fabrication method—termed microfluidic emulsion templating—is facile, cost-effective, scalable and can precisely engineer the structural topographies. The robust omniphobic surface is expected to open up new avenues for diverse applications due to its mechanical and chemical robustness, transparency, reversible Cassie–Wenzel transition, transferability, flexibility and stretchability.

Droplet Breakup in Expansion-contraction Microchannels

We investigate the influences of expansion-contraction microchannels on droplet breakup in capillary microfluidic devices. With variations in channel dimension, local shear stresses at the injection nozzle and focusing orifice vary, significantly impacting flow behavior including droplet breakup locations and breakup modes. We observe transition of droplet breakup location from focusing orifice to injection nozzle, and three distinct types of recently-reported tip-multi-breaking modes. By balancing local shear stresses and interfacial tension effects, we determine the critical condition for breakup location transition, and characterize the tip-multi-breaking mode quantitatively. In addition, we identify the mechanism responsible for the periodic oscillation of inner fluid tip in tip-multi-breaking mode. Our results offer fundamental understanding of two-phase flow behaviors in expansion-contraction microstructures, and would benefit droplet generation, manipulation and design of microfluidic devices.

Mechano-regulated surface for manipulating liquid droplets

The effective transfer of tiny liquid droplets is vital for a number of processes such as chemical and biological microassays. Inspired by the tarsi of meniscus-climbing insects, which can climb menisci by deforming the water/air interface, we developed a mechano-regulated surface consisting of a background mesh and a movable microfibre array with contrastive wettability. The adhesion of this mechano-regulated surface to liquid droplets can be reversibly switched through mechanical reconfiguration of the microfibre array. The adhesive force can be tuned by varying the number and surface chemistry of the microfibres. The in situ adhesion of the mechano-regulated surface can be used to manoeuvre micro-/nanolitre liquid droplets in a nearly loss-free manner. The mechano-regulated surface can be scaled up to handle multiple droplets in parallel. Our approach offers a miniaturized mechano-device with switchable adhesion for handling micro-/nanolitre droplets, either in air or in a fluid that is immiscible with the droplets.