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

Abstract

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.

Keywords: assembly; digital microfluidics; sorting; targeted drug delivery; triggered release.

Figure 1

Classification of fabrication strategies, manipulation techniques, and applications of core–shell particles.

Figure 2

Typical applications of core–shell particles. (A) Chitosan core–shell particle for drug release; (B) Core–shell particles for biomolecule sensing and release; (C) Carbon-platinum-PANI (polyaniline) core–shell particles as catalysis; (D) Core–shell particle for methylene blue detection; (E) Schematics showing enhanced ultrasound imaging of blood capillaries after microbubble infusion.

Figure 3

Fabrication techniques for core–shell particles. (A) Core–shell particle fabrication using (i) a two-step microfluidic method and (ii) a one-step method; (B) Experimental setup of gas-shearing method for core–shell particles; (C) Sol–gel method for silica core–shell particles; (D) Electrospray method; (E) Core–shell particles formation by self-assembly: (i) Oil-suspended water droplets and particles. (ii) Particles adsorb at oil–water interface to form core–shell particle. (iii) Transferring formed core–shell particles to water by centrifugation.

Figure 4

Assembly of micro- and nanoparticles. (A) Assembly of particles on patterned surface; (B) Formation of core–shell particles with layer-by-layer assembly on Pickering emulsion surfaces: (i) Poly (sodium styrene sulfonate) particles suspended in water, (ii) Surface modification, (iii) Emulsification to form oil-in-water Pickering emulsion; (C) 2D assembly of particles suspended in a medium: (i) Random arrangement of particles in thick layer of medium, (ii) Particles assembly into 2D as medium evaporates; (D) Suspended magnetic particles successively arrange into 1D chain, 2D sheet, and 3D crystal with increasing magnetic field strength and particle concentration; (E) Assembly of suspended particles in a microfluidic channel using surface acoustic wave; (F) Experimental setup of optofluidic assembly of particles.

Figure 5

List of criteria and methods for sorting core–shell particles.

Figure 6

Particle sorting methods. (A) Microparticle sorting by pinched flow fractionation; (B) Microparticle sorting by deterministic lateral displacement; (C) Particle sorting by inertial microfluidic separation; (D) Schematics illustrate microfilter arrangements for particle sorting: (i) Dead-end filter, (ii) Crossflow filter; (E) Density-based sorting of particles in acoustic field; (F) Magnetic particle separation based on their magnetic properties.

Figure 7

Triggered release of core−shell particles. (A) Schematics of triggered release of core−shell particles using various heating strategies; (B) Physical rupturing of shell; (C) Core−shell particles encapsulating insulin and enzyme, enzymatic action on glucose coverts it into gluconic acid, high pH causes shell expansion and triggers release; (D) Ionic concentration tunes electrostatic forces to control the expansion of the shell.