Electrostatically Directed Self-Assembly of Ultrathin Supramolecular Polymer Microcapsules

Abstract

Supramolecular self-assembly offers routes to challenging architectures on the molecular and macroscopic scale. Coupled with microfluidics it has been used to make microcapsules-where a 2D sheet is shaped in 3D, encapsulating the volume within. In this paper, a versatile methodology to direct the accumulation of capsule-forming components to the droplet interface using electrostatic interactions is described. In this approach, charged copolymers are selectively partitioned to the microdroplet interface by a complementary charged surfactant for subsequent supramolecular cross-linking via cucurbit[8]uril. This dynamic assembly process is employed to selectively form both hollow, ultrathin microcapsules and solid microparticles from a single solution. The ability to dictate the distribution of a mixture of charged copolymers within the microdroplet, as demonstrated by the single-step fabrication of distinct core-shell microcapsules, gives access to a new generation of innovative self-assembled constructs.

Keywords: microcapsules; microfluidics; microstructures; self-assembly; supramolecular materials.

Figure 1

Formation of microcapsules from microfluidic droplets. A) Transmission optical image of the generation of monodisperse water-in-oil microdroplets (Ø = 79.0 ± 0.7 μm) at a 60 μm microfluidic flow-focusing junction. B) A schematic of supramolecular microcapsule formation between charged copolymers at the interface of a microdroplet. C) Transmission image of partially collapsed, ultrathin polymer microcapsules. D) Schematic and chemical structure of the cucurbit[8]uril macrocycle (CB[8]). E) Chemical structures of charged dopants: carboxylate-terminated Krytox (K⁽⁻⁾) and ammonium-terminated Krytox (K⁽⁺⁾). F) Chemical structures of the complimentary-functionalized copolymers 1A⁽⁻⁾ and 1B⁽⁻⁾ (net negative charge) and 2A⁽⁺⁾ and 2B⁽⁺⁾ (net positive charge).

Figure 2

Electrostatically directed self-assembly of charged copolymers. A) Laser-scanning confocal fluorescent images and B) fluorescence intensity profiles of microdroplets containing an aqueous solution of fluorescein-labeled, negatively charged copolymer 1A⁽⁻⁾, [azo] = 60 × 10⁻⁶ m. Upon increasing the concentration of the positively charged Krytox, K⁽⁺⁾ within the carrier oil from 0.0 to 1.0 wt% the complementary charged copolymer is observed to accumulate at the droplet interface, templating microcapsule formation. C) Transmission images of evaporated microdroplets containing copolymers 1A⁽⁻⁾, 1B⁽⁻⁾, and CB[8] [azo:MV:CB[8] = 60:60:60 × 10⁻⁶ m]. As the concentration of K⁽⁺⁾ increases the morphology transitions from smooth, solid microparticles (1–3) to hollow, collapsed microcapsules (5–7).

Figure 3

Interferometric mapping of microcapsule thickness. A) Reflectance image of a dried, collapsed microcapsule made from of 2A⁽⁺⁾, 2B⁽⁺⁾, and CB[8] [stil:MV:CB[8] = 60:60:60 × 10⁻⁶ m]. B) Thickness map of the microcapsule as determined by optical interferometry, with a 1.5 μm spot size and automated microscope movement, and C) overlaid.

Figure 4

Microcapsule inflation and tracking copolymer accumulation within the microdroplet. A) Rehydration of 1A⁽⁻⁾ ⊂ CB[8] ⊂1B⁽⁻⁾ microcapsules containing dextran cargo (10 × 10⁻⁶m, 70 kDa) confirms that the polymeric skin is retained. B) Real-time laser-scanning confocal fluorescent images of microdroplets containing an aqueous solution of fluorescein-labeled, negatively charged copolymer 1A⁽⁻⁾, [azo] = 60 × 10⁻⁶ m. In the presence of K⁽⁺⁾ (1.0 wt%) diffusion of 1A⁽⁻⁾ to the droplet interface rapidly progresses as it flows along the microfluidic channel, from (1) flow focus to (2) the channel outlet; (3) after leaving the delivery tubing near-quantitative diffusion to the interface had occurred. Dashed lines mark channel boundaries. C) Fluorescence intensity profiles across a transect of a microdroplet as a function of the time-lapsed since generation at the flow-focusing junction, illustrating the kinetics of the rapid diffusion to the droplet interface.

Figure 5

Dynamic control of charged copolymer within the microdroplet. A) Transmission image of the microdroplet trap (top left); aqueous microdroplets of rhodamine-labeled 2B⁽⁺⁾ [MV = 60 × 10⁻⁶ m] were held within the trap by a continuous oil flow (250 μL h⁻¹). Real-time laser-scanning confocal fluorescent images of the trapped microdroplets within a neutral oil flow. Upon switching to a complimentarily charged surfactant (1.0 wt% K⁽⁻⁾) rapid diffusion to the droplet interface was observed, with partitioning complete in 24 s. B) The location of orthogonally charged copolymers 1A⁽⁻⁾ and 2B⁽⁺⁾ [azo:MV = 60:60 × 10⁻⁶ m] can be independently manipulated within the microdroplet, allowing for selective assembly at the interface.

Figure 6

Table correlating the distribution of fluorescent copolymer in the microdroplet (left) with the resultant microstructure formed upon evaporation (right), as a function of the charge at the droplet interface. A) Complementary: Negative copolymers 1A⁽⁻⁾ and 1B⁽⁻⁾ (fluorescein-labeled, green) were found to exclusively form a hollow microcapsule in the presence of K⁽⁺⁾ [azo:MV:CB[8] = 60:60:60 × 10⁻⁶ m]. Conversely, positive copolymers 2A⁽⁺⁾ and 2B⁽⁺⁾ (rhodamine-labeled, red) were found to exclusively form a microcapsule with K⁽⁻⁾ [stil:MV:CB[8] = 60:60:60 × 10⁻⁶ m]. B) Orthogonal: A mixed solution of negative 1A⁽⁻⁾ and positive 2B⁽⁺⁾ was found to exclusively form a hollow microcapsule in the presence of K⁽⁻⁾ [azo:MV:CB[8] = 60:60:60 × 10⁻⁶ m]. Conversely, a mixed solution of positive 2A⁽⁺⁾ and negative 1B⁽⁻⁾ exclusively formed microcapsules with K⁽⁺⁾ [stil:MV:CB[8] = 60:60:60 × 10⁻⁶ m]. C) Core–shell: A mixed solution of 1A⁽⁻⁾, 1B⁽⁻⁾, 2A⁽⁺⁾, and 2B⁽⁺⁾ formed homogenous microparticles under neutral conditions. However, core–shell microcapsules were formed with both K⁽⁺⁾ and K⁽⁻⁾ dopants, with the outer shell comprising of either 1A⁽⁻⁾ ⊂ CB[8] ⊂ 1B⁽⁻⁾, or 2A⁽⁺⁾ ⊂ CB[8] ⊂ 2B⁽⁺⁾, respectively [CB[8]:guests = 120:60 × 10⁻⁶ m]. D) Transmission images of the evaporative formation of a core–shell microcapsule containing 160 × 10⁻⁶ m of dextran cargo (70 kDa) and E) laser-scanning confocal fluorescence image of this core–shell microcapsule during hydration at t = 0, 15, and 30 min, illustrating the partitioned copolymers within the cross-linked microstructure (shell: 2A⁽⁺⁾ ⊂ CB[8] ⊂ 2B⁽⁺⁾, core: 1A⁽⁻⁾ ⊂ CB[8] ⊂ 1B⁽⁻⁾).