Precision Particles

Research Overview

The DeSimone lab pioneered the ability to manufacture particles with absolute, independent control over size, shape, and composition, a level of precision that conventional particle-synthesis routes could not provide. Early efforts leveraged heterogeneous polymerizations, including emulsion polymerization in supercritical CO₂, to produce stable colloids of submicron, water-soluble polymer particles whose diameters could be tuned through reaction conditions (Macromolecules, 2005). While such emulsion and microemulsion methods offered control over particle size, they left particle shape dictated by interfacial energetics rather than design. To overcome this limitation, the lab developed Particle Replication In Non-wetting Templates (PRINT), a top-down, lithography-derived molding technology that uses low-surface-energy fluoropolymer molds to fabricate monodisperse particles with arbitrary, precisely defined geometries — from sub-200 nm nanoparticles to complex micron-scale objects — while enabling straightforward encapsulation of proteins, nucleic acids, and small-molecule therapeutics (JACS, 2005). The lab subsequently extended particle molding to produce fillable, hollow microparticles and other complex three-dimensional microstructures for controlled cargo loading and release (Science, 2017). The scalability and design flexibility of this platform were commercialized through Liquidia Technologies for engineered vaccines and inhaled therapeutics, and the underlying principles directly seeded the lab's current roll-to-roll manufacturing of shape-specific particles (Nature, 2024).