Nanocomposite capsules with directional, pulsed nanoparticle release

Nanocomposite microcapsules with bicontinuous internal morphology release nanoparticles in directional bursts.

 movie S1 (.mp4 format). Video depicting the mechanism and kinetics of solvent extraction of 1% (w/v) NaPSS + 10% (w/v) SiO2 aqueous droplet of 250 μm radius in neat ethyl acetate over a period of 360 s (video 10 times faster).  movie S2 (.avi format). Video showing the immersion of bicontinuous capsule above in deionized water (pH 5 to 6), depicting the pulsed release of nanoparticle clusters, over a time scale of 10,000 s (video 300 times faster).  movie S3 (.avi format). As above, following immersion in deionized water with pH 9.35 over a time scale of 7000 s (video 200 times faster; air bubbles result from the immersion of the dried capsule in water and are not a result of dissolution).  movie S4 (.mp4 format). Video depicting the mechanism and kinetics of solvent extraction of 1% (w/v) NaPSS + 0.3% (w/v) SWCNT aqueous droplet of ≃250 μm radius in neat ethyl acetate over a period of 250 s (video 25 times faster).  movie S5 (.mp4 format). Video depicting the mechanism and kinetics of solvent extraction of 1% (w/v) NaPSS + 0.025% (w/v) Au nanoparticle aqueous droplet of ≃250 μm radius in neat ethyl acetate over a period of 250 s (video 10 times faster).
Supplementary Materials note S1. Microfluidic device fabrication Microfluidic devices were fabricated by frontal photopolymerization of a commercially-available multifunctional thiolene prepolymer, employed as a negative photoresist. The photoresist was polymerized between pre-drilled glass plates, and selectively developed to yield a solventresistant microdevice. Specifically, photomasks were designed using AutoCAD and printed on a high resolution photographic film with 40,000 dpi resolution (microlithography services, UK). Glass slides (corning, (75 x 25 x 1) mm 3 ) were first cleaned with acetone and allowed to dry, and then inlet and outlet holes were drilled with a carbide tipped drill bit.  Figure S1, based on turbidity measurements and visual inspection of the ternary mixtures.
For improved compositional accuracy, 40 ml of each composition was prepared. Single-phase homogeneous regions are indicated as 'miscible' while phase separated regions with two phase (solid-gas) and co-existing three phase 'solid-gas-liquid' compositions are indicated as 'immiscible'. All data presented in this work correspond to initial mixture compositions in the 'miscible' region. A comparison between the rates of reduction in droplet size and solute diffusion can be provided by the dimensionless Péclet number, which we write as P e = ER/D 0 where E is the drying velocity, R is the droplet radius and D 0 is the diffusion coefficient. We estimate E from the initial dR/dt during isotropic reduction in droplet volume, and D 0 of the silica nanoparticle in the droplet using the Stokes-Einstein relation D 0 = k B T /6πηR, taking the silica nanoparticle radius R ≈ 11 nm and the viscosity η to be that of the ternary polymer/silica/H 2 O mixture at temperature T; k B is the Boltzmann constant. We find initial values of Pe between 3 -20 in qualitative agreement with observed formation of capsule skin at early times and subsequent deformation of the capsule. Upon extraction, η evidently increases thus further increasing P e, although such estimations are not expected to hold as the nanoparticle concentration increases, and upon agglomeration and demixing.

note S4. Additional analysis for data shown in main paper
In Figure S2 we show comparative R(t) data for pure H 2 O, 1 w/v% NaPSS (P), 10 w/v% silica (S), and 1 w/v% NaPSS + 10 w/v% droplets with initial droplet radius 140 µm. We find that as expected, the final capsule size, R ∞ depends on the solute content. We analyse the area, and deformation parameter (D= (R major + R minor )/(R major -R minor )) in Figure   S3 for data shown in Figure 3A (main paper). Figure S4A is the corresponding R minor (t) plots for data shown in Figure 3B (main paper). At constant C SiO 2 (12 w/v%), an increase in C NaPSS results in elongated capsules, as discussed in the main paper and shown in Figure   S4B. While at constant C NaPSS and C SiO 2 ≤ 0.5 w/v%, deformed capsules are produced, an increase in C SiO 2 leads to a decrease in anisotropy yielding spherical capsules instead with dimples. Figure S5 shows the corresponding R minor (t) plots for data shown in Figure 3C (main paper). The inset in Figure S5 shows the dependence of capsule shell thickness on C SiO 2 . At C SiO 2 ≤ 0.5 w/v%, capsules formed possess thin shells prone to deformation. Thick shelled capsules formed at high C SiO 2 (≥ 2 w/v%) resist deformation due to high bending and stretching energies, as discussed in the main paper. In Figure S6, we show time resolved R major , R minor , and deformation profiles for droplets with constant C SiO 2 of 5 w/v% (Figures S6A-C), and 10 w/v% (Figures S6D-F). At C SiO 2 ≤ 5 w/v% and C NaPSS 5 w/v%, dense capsules are formed and elongation is minimized. Deformation increases with C NaPSS for C SiO 2 ≥ 10 w/v%.
+ 12 w/v% silica droplet. Droplet extraction kinetics is analysed in terms of deformation and area for a droplet with high polymer and silica content (5 w/v% NaPSS + 12 w/v% SiO 2 ) with initial droplet radius 140 µm. R minor data for Figure 2C (main paper). Effect of silica concentration on extraction kinetics at initial NaPSS (1 w/v%) concentration; results for NP of 2-20 w/v% overlap. The inset shows the dependence of the ratio of capsule shell thickness, T, to final capsule radius R ∞ on C SiO 2 . F E extraction for various NaPSS/silica composition. The effect of polymer concentration on extraction kinetics, at initial C SiO 2 5 w/v % (A)-(C) and 10 w/v % of silica is shown in (D)-(F)respectively; Pure H 2 O and NaPSS 1 w/v% are included for reference. R major and R minor are shown separately for clarity. The deformation parameter tracks the elongation of the capsules during the extraction process.
fig. S6. Evolution of droplet radius and deformation parameter with time during note S5. Additional SEM images of capsules Additional SEM images illustrate the variety of anisotropic capsules that are attainable in our system for concentrations studied. External morphologies are shown in Figure S7 and internal microstructure in Figure S8 for selected compositions. Wide-view microscopy images of capsules obtained from specific compositions within the morphology diagram are shown in Figure S10 to demonstrate scalability and reproducibility of the capsule formation process.
We take a horizontal line across the morphology map at C NaPSS , 1 w/v% NaPSS (P) and show high resolution images of the capsule shell at varying C SiO 2 in Figure S9. The thickness of the capsule shell increases with increasing C SiO 2 . polymer-nanoparticle capsules as a function of NaPSS and SiO 2 content. (A) At low C NaPSS , (3 w/v%), and C SiO 2 (5 w/v %), thin shelled capsules are formed (B) C NaPSS , (5 w/v%), and C SiO 2 (5 w/v %) dense porous capsules are formed. The internal structure for bicontinuous capsules obtained from droplets with composition (C)-(D) 1 w/v% NaPSS + 10 w/v% SiO 2 and (E)-(F) 3 w/v% NaPSS + 10 w/v% SiO 2 and 3 w/v% NaPSS + 12 w/v% SiO 2 respectively. 1 % P neat polymer, and composite polymer-nanoparticle capsules as a function of NaPSS and SiO 2 content. Porous thin shelled spherical capsules are formed from neat polymer droplets with concentration (A) C NaPSS , 3 w/v%, thin shelled capsules with largo cargo capacity for nanoparticle clusters are formed at (B) 1 w/v% NaPSS + 5 w/v% SiO 2 and bicontinuous capsules with internal scaffold structure is formed at 1 w/v% NaPSS + 5 w/v% SiO 2 . (D) Dependence of shell thickness on nanoparticle concentration at initial C NaPSS , 1 w/v%. We have examined the dependence of the nanoparticle release mechanism on capsule morphology in Figure 5 of the main paper. In Figure S12, we show additional optical images of the dissolution of neat polymer capsules produced from 3 w/v% NaPSS initial composition, and the instantaneous release of nanoparticle clusters from a composite polymer-nanoparticle capsule produced from a droplet with 3 w/v% NaPSS + 10 w/v% SiO 2 initial composition. capsules. (A)Phase diagram of capsule morphologies obtained from polymer-nanoparticle mixtures as a function of C NaPSS and C SiO 2 . The empty grey and green squares represent initial droplet composition of 3 w/v% NaPSS, and 3 w/v% NaPSS+ 10 w/v% SiO 2 respectively. While (B) neat polymer capsules swell and dissolve over time (C) nanoparticle clusters are spontaneously released from composite polymer-nanoparticle capsule.
fig. S12. Dissolution of 3 w/v% NaPSS, and 3 w/v% NaPSS+ 10 w/v% SiO note S8. Spatio-temporal analysis of pulsed release of NP clusters from bicontinuous capsules immersed in DI water (pH 5 -6) We have examined the spatial distribution of release sites at the surface of a representative capsule, to resolve the number of active sites and any possible spatial correlation between them. We take as a reference bicontinuous capsules produced from droplets with 1 w/v% NaPSS + 10 w/v% SiO 2 and 1 w/v% NaPSS + 15 w/v% SiO 2 initial composition and final radius, R∞, 250 µm. These data correspond to Figure 5D of the main paper, and are obtained following immersion in DI H 2 O, whose pH is 5-6. The frequency of these pulsed bursts is examined in Figure S9 for the three most active sites, indicated by the colored markers on a capsule produced from a droplet with 1 w/v% NaPSS + 10 w/v% SiO 2 initial composition is shown in Figure S13. The location of active release sites is graphically depicted in Figure S14 over three representative time intervals. Capsules are found to eject nanoparticle clusters from approximately 5-10 sites throughout their release process. These sites are found to be relatively uniformly distributed around the capsule surface. While some sites yield a single burst, others exhibit multiple bursts. The time interval between bursts evidently varies from site to site and over time, for a single site, however these occur between approximately 100 s to 1000 s intervals. We interpret these pulses as arising from the osmotic pressure build-up within the capsule and, possibly, the sequential rupture between internal compartments or pockets during release. The overall release profile is thus determined by the overlap of pulsed ejections from multiple sites over an exceptionally prolonged timescale, compared to those of capsules formed from the neat constituents. The dependence of the nanoparticle release intensity and release rate on the pH of the dissolution medium is shown in Figure S15 and Figure S16 for capsules produced from droplets with 1 w/v% NaPSS + 10 w/v% SiO 2 and 1 w/v% NaPSS + 15 w/v% SiO 2 initial composition and with final radius, R∞, 250 µm. At C SiO 2 , 15 w/v%, the release intensity is less sensitive to pH. Furthermore, no release is observed for composite capsules produced from droplets with 1 w/v% NaPSS + 20 w/v% SiO 2 initial composition. This is most likely because of irreversible aggregation of the silica nanoparticles at high comcentration. sules obtained from 1 w/v% NaPSS + 10 w/v% SiO 2 , and 1 w/v% NaPSS + 15 w/v% SiO 2 initial droplet composition. Active sites of cluster release on capsule surface at time intervals (I) 0-400 s, (II) 400-900 s, (III) 900-2000 s, indicated by each concentric circle with corresponding analysis of the release intensity from respective sectors of the composite capsule. Capsules shown are obtained from (A) 1 w/v% NaPSS + 10 w/v% SiO 2 and (B)1 w/v% NaPSS + 15 w/v% SiO 2 initial droplet composition, R∞250µm. Data shown are obtained from capsule immersion in DI H 2 O. (A) is reproduced from Figure 5D of the main paper. from 1 w/v% NaPSS + 10 w/v% SiO 2 initial droplet composition.(A) Phase diagram of capsule morphologies obtained from polymer-nanoparticle mixtures as a function of C NaPSS and C SiO 2 , the white empty square represents initial droplet composition of 1 w/v% NaPSS + 10 w/v% SiO 2 . (B) Optical images of dissolution of capsules of 1 w/v% NaPSS + 10w/v% SiO 2 at pH 5. The (C) release intensity and (D) release rate of the nanoparticle clusters from the bicontinuous scaffold is dependent on the pH of the dissolution medium. from 1 w/v% NaPSS + 15 w/v% SiO 2 initial droplet composition. (A) Phase diagram of capsule morphologies obtained from polymer-nanoparticle mixtures as a function of C NaPSS and C SiO 2 , the white empty square represents initial droplet composition of 1 w/v% NaPSS + 15 w/v% SiO 2 . (B) Optical images of dissolution of capsules of 1 w/v% NaPSS + 15w/v% SiO 2 at pH 5. The (C) release intensity and (D) release rate of the nanoparticle clusters from the bicontinuous scaffold is dependent on the pH of the dissolution medium.
fig. S16. Analysis of release of nanoparticle clusters from a capsule obtained note S9. Impact of payload type on composite capsule morphology and release profile To investigate the generality of our approach, we demonstrate the encapsulation of nanofillers, single walled carbon (SWCNTs) nanotubes and Au nanoparticles, within polymer capsules.
Optical images showing the time series of solvent extraction for droplets with composition 1 w/v% NaPSS + 0.3 w/v% SWCNTs and 1 w/v% NaPSS + 0.025 w/v% Au nanoparticles are shown in Figure S17A-B. As phase separation between polymer and nanofiller does not take place, unlike in the silica mixture, the receding liquid-liquid interface entraps the cargo and polymer phase inversion takes place as in the case of neat polymer. As a result, the resulting composite capsules remain largely spherical at the compositions investigated. The composite capsule microstructure is similar to that obtained from a neat polymer droplet (shown in SI Figure S9 and is not largely modified by the SWCNTs or Au nanoparticles, the payloads are therefore kinetically trapped within the polymer matrix. The internal microstructure of the composite capsules is shown in Figure S17C-D. The formation of bicontinuous internal morphologies evidently requires the crossing of the spinodal line along the solvent extraction pathway, which can be engineered to match the ternary solution thermodynamics as in the case of silica-polymer mixtures, but does not readily take place. Similarly, the formation of non-isotropic capsules requires the emergence of a (composite) stiff shell during the extraction process, which deforms -by bending, folding or crumpling -upon further volume reduction. The release of the entrapped SWCNT and Au payloads from the NaPSS/SWCNT and NaPSS/Au composite capsules is thus found to be mediated by the dissolution of the polymer matrix, which occurs within timescales of minutes instead many hours, as observed in SiO 2 /NaPSS capsules, and shown in Figure S18.