Synthesis of size-tunable polymeric nanoparticles enabled by 3D hydrodynamic flow focusing in single-layer microchannels - PubMed (original) (raw)

Synthesis of size-tunable polymeric nanoparticles enabled by 3D hydrodynamic flow focusing in single-layer microchannels

Minsoung Rhee et al. Adv Mater. 2011.

No abstract available

Figures

Figure 1

(a) Concept of device for 3D hydrodynamic focusing (not to scale) consisting of three sequential inlets for vertical focusing and a separate inlet for side sheath flows (not shown). The cross-sectional views in the inset show the vertically focused stream profile (left) and the heterogeneous 3D hydrodynamic focusing where the sample flow is isolated both horizontally and vertically (right). (b) TEM images of PLGA-PEG NPs obtained from PLGA27K-PEG5K at 10 mg mL-1 in ACN (scale bar 100 nm), PLGA45K-PEG5K at 30 mg mL-1 in ACN (scale bar 100 nm) and PLGA95K-PEG5K at 30 mg mL-1 in ACN (scale bar 200 nm) using 3D HFF with the flow ratio of Polymer:ACN = 3:7 and organic:water = 1:5. Average NP sizes are 33.8, 55.0, and 200 nm, respectively.

Figure 2

Comparison of 3D HFF (f = 0.3), 2D HFF, and bulk nanoprecipitation of PLGA-PEG NPs under different conditions with the flow ratio of organic:water = 1:10. (a) Representative channel images of the device during synthesis of PLGA-PEG NPS by 3D HFF and 2D HFF for various MW precursors, showing aggregation in the case of 2D HFF. All micrographs were captured after ~500 s of operation (channel width 20 μm). (b) Effect of the PLGA-PEG precursor concentration on the final NP sizes depending on the MW of the precursors and the choice of a synthesis method. X = Clogging of channel within 3 minutes of operation. * = Aggregation of polymer in channel observed after 5-10 minutes of operation. # = Aggregation of polymer in channel observed after >10 minutes of operation. (c) Size distributions by volume fraction of PLGA95K-PEG5K NPs prepared by microfluidic 3D HFF, 2D, and bulk mixing methods for the precursor concentrations of 10 and 50 mg/mL, respectively. Aggregated particles are found in the 1,000-10,000 nm range. (d) Phase space of 3D HFF operation parameters (Pe* and f) for synthesis of PLGA NPs from pure PLGA70K precursors (10 mg mL-1). Solid green line represents condisitons where Pef*=10 and dashed red line represents conditions under which the PLGA70K precursor reaches a critical wall concentration (1 mg mL-1) that results in aggregation. Both lines delineate conditions that result good synthesis of NPs (Phase I) from those that are susceptible to aggregation (Phase II). Symbols indicate experimental data for the synthesis of PLGA70K NPs. (O: reproducible, successful NP synthesis, X: aggregation with microparticle formation, Δ: mild or occasional aggregation). Inset shows simulated concentration profiles at the starting poirnt of nanoprecipitation under the conditions where flow rates (_u_max) are different but f is the same for Phase I (*) and Phase II (**), respectively.

Figure 3

(a) 3D simulations with different channel aspect ratios (w/h); 3.33 (left) and 0.83 (right), respectively. Perspective views of the channel with the width of 200 μm and the inlet of 150 μm. Only the left halves about the symmetry plane are shown. (b) Simulated cross-sectional views for two different inlet hole diameters at a fixed channel aspect ratio (w/h = 3.33). (c) 3D simulations for a channel of w = 100 μm and h = 100 μm, showing off–centered inlet (left), well aligned inlet (center), and slightly larger inlet (right). (d) Confocal micrographs showing cross-sectional views of vertical focusing before (A) and after (B) horizontal focusing. The top panel shows a top-view of the system near the lateral squeezing cross juction. In the bottom left panel, off-centered holes directly compare with the left panel in (c). The bottom center panel shows vertical focusing occurred in the channel of w/h = 3.33 while the sequential inlet hole size was slightly smaller. The bottom right panel shows vertical focusing occurred in the channel of w/h = 1.0.

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Synthesis of size-tunable polymeric nanoparticles enabled by 3D hydrodynamic flow focusing in single-layer microchannels - PubMed (original) (raw)