Direct Fabrication and Harvesting of Monodisperse, Shape-Specific Nanobiomaterials

TLDR

PRINT is a versatile, general method capable of fabricating chemically diverse particles compatible with delicate biological agents, overcoming the film‑related limitations that hindered soft lithography. The study presents PRINT, a top‑down method that provides absolute control over particle size, shape, and composition. PRINT employs low‑surface‑energy fluoropolymer molds to eliminate residual interconnecting films, enabling precise particle fabrication. PRINT produced monodisperse particles from sub‑200 nm to micron scale across multiple polymers and successfully encapsulated proteins, DNA, and small‑molecule therapeutics, demonstrating its potential for next‑generation drug‑delivery particles.

Abstract

A versatile "top-down" method for the fabrication of particles, Particle Replication In Nonwetting Templates (PRINT), is described which affords absolute control over particle size, shape, and composition. This technique is versatile and general enough to fabricate particles with a variety of chemical structures, yet delicate enough to be compatible with sophisticated biological agents. Using PRINT, we have fabricated monodisperse particles of poly(ethylene glycol diacrylate), triacrylate resin, poly(lactic acid), and poly(pyrrole). Monodisperse particle populations, ranging from sub-200 nm nanoparticles to complex micron-scale objects, have been fabricated and harvested. PRINT uses low-surface energy, chemically resistant fluoropolymers as molding materials, which eliminates the formation of a residual interconnecting film between molded objects. Until now, the presence of this film has largely prevented particle fabrication using soft lithography. Importantly, we have demonstrated that PRINT affords the simple, straightforward encapsulation of a variety of important bioactive agents, including proteins, DNA, and small-molecule therapeutics, which indicates that PRINT can be used to fabricate next-generation particulate drug-delivery agents.