In-fiber production of polymeric particles for biosensing and encapsulation

Abstract

Polymeric micro-and nanoparticles are becoming a mainstay in biomedicine, medical diagnostics, and therapeutics, where they are used in implementing sensing mechanisms, as imaging contrast agents, and in drug delivery. Current approaches to the fabrication of such particles are typically finely tuned to specific monomer or polymer species, size ranges, and structures. We present a general scalable methodology for fabricating uniformly sized spherical polymeric particles from a wide range of polymers produced with complex internal architectures and continuously tunable diameters extending from the millimeter scale down to 50 nm. Controllable access to such a wide range of sizes enables broad applications in cancer treatment, immunology, and vaccines. Our approach harnesses thermally induced, predictable fluid instabilities in composite core/cladding polymer fibers drawn from a macroscopic scaled-up model called a "preform." Through a stack-and-draw process, we produce fibers containing a multiplicity of identical cylindrical cores made of the polymers of choice embedded in a polymer cladding. The instability leads to the breakup of the initially intact cores, independent of the polymer chemistry, into necklaces of spherical particles held in isolation within the cladding matrix along the entire fiber length. We demonstrate here surface functionalization of the extracted particles for biodetection through specific protein-protein interactions, volumetric encapsulation of a biomaterial in spherical polymeric shells, and the combination of both surface and volumetric functionalities in the same particle. These particles used in distinct modalities may be produced from the desired biocompatible polymer by changing only the geometry of the macroscopic preform from which the fiber is drawn.

Digital design of multimaterial photonic particles

“…If the core diameter is much smaller than that of the shell d core =d shell 1, then the resulting breakup period of the core may-in turn-be significantly smaller than that of the shell. Consequently, instead of the desired core-shell structure, multiple smaller core particles forming a linear chain extending between the antipodes of the particle are obtained inside a single shell (28,40). We confirm these predictions experimentally (SI Appendix, Fig.…”

“…The dynamics of the breakup process is shown in Movie S1, where six parallel cores in a fiber are thermally treated and undergo a physical transformation from microthreads to a 2D array of spheres. We focus here on thermally compatible combinations of polymers (28) and soft glasses (26,27,36,37) that afford high optical refractive-index contrasts, but a broader range of materials can be exploited in this process, such as crystalline semiconductors including silicon and germanium (38) and even globular biomaterials (28).…”

“…Although the thicknesses of the layers in the particle are related deterministically to those of the cylindrical shells in the drawn fiber (28,40), the dynamics of the PRI nevertheless constrains the relative shell diameters for which the breakup results in the intended layered structure. It is well established from the classic Tomotika model that the breakup period of a viscous thread embedded in a viscous matrix is proportional to the diameter of the thread (39).…”

“…The key to addressing the challenge of particle digital design is exploiting a recently discovered in-fiber fluid instability (26)(27)(28) that produces spherical particles having-in principle-arbitrary internal structure. A centimeter-scale axisymmetric cylindrical "core" rod is assembled as a prototype of the intended particle structure in a LEGO-like procedure from prefabricated segments of different materials, which is then embedded in a cladding matrix to form a "preform" (29)(30)(31).…”

“…A centimeter-scale axisymmetric cylindrical "core" rod is assembled as a prototype of the intended particle structure in a LEGO-like procedure from prefabricated segments of different materials, which is then embedded in a cladding matrix to form a "preform" (29)(30)(31). A fiber that is thermally drawn from this preform with reduced transverse feature size defines the initial conditions for a cylinder-to-sphere geometric transformation by thermally inducing the Plateau-Rayleigh capillary instability (PRI) (32,33) at the heterogeneous interfaces along the whole fiber length (26)(27)(28). Because the geometric morphing associated with this fluid instability is predictable, the axially symmetric core is converted into spherical particles with a target architecture that follows from the macroscopic preform structure.…”