Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods
Abstract
:1. Introduction
2. Results
2.1. Silk Nanoparticle Physicochemical Characterization
2.1.1. Volumetric Scale-Up in Semi-Batch Format
2.1.2. Volumetric Scale-Up by Parallelization in Microfluidic Format
2.2. Secondary Structure Measurement
2.3. Thermal Analysis
2.4. The Impact of Volumetric Scale on the Colloidal Stability of Silk Nanoparticles
3. Discussion
3.1. The Impact of Volumetric Scale on Reproducibility of Semi-Batch Silk Nanoprecipitation
3.2. The Reproducibility of Silk Nanoprecipitation in a Parallelizable Microfluidic Format
3.3. The Production Rates of Silk Nanoprecipitation in the Semi-Batch and Microfluidic Formats
3.4. The Impact of Volumetric Scale on the Colloidal Stability of Silk Nanoparticles
4. Materials and Methods
4.1. Regeneration of B. mori Silk
4.2. General Manufacture of Silk Nanoparticles in Semi-Batch Format
4.3. Volumetric Scale-Up of Semi-Batch Silk Nanoparticle Manufacture
4.4. Dual Indicator System for Mixing Time in the Semi-Batch Format
4.5. Semi-Batch Droplet Analysis
4.5.1. Volume and Time of Flight
4.5.2. Fluid Velocity, Droplet Diameter, and Diffusion Scales
4.6. Manufacture of Silk Nanoparticles in Microfluidic Format
4.7. Yield of Silk Nanoparticles
4.8. Physicochemical Characterization of the Silk Nanoparticles and Stability in Water
4.9. Secondary Structure Measurements of Silk Nanoparticles
4.10. Thermal Analysis of Silk Nanoparticles
4.11. Scanning Electron Microscopy of Silk Nanoparticles
4.12. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Semi-Batch Format | Microfluidic Format | |||
---|---|---|---|---|
Total Volume/mL | Stirring Rate/rpm | Mixing Time/s | Residence Time/ms | Mixing Time/ms |
5 | 400 | 8.4 ± 4.4 | 120 | 21 |
30 | 400 | 29.4 ± 6.0 |
Semi-Batch Format | Microfluidic Format | |||||
---|---|---|---|---|---|---|
Needle Internal Diameter/mm | Flow Rate/mL min−1 | Residence Time/ms | Maximum Shear Rate/s−1 | Re | Maximum Shear Rate/s−1 | Re |
0.33 | 1.00 | 43 | 4724 | 2.4 | 80,114 | 40 |
Thermal Property | Semi-Batch | Microfluidic | Negative Silk II Control | ||||||
---|---|---|---|---|---|---|---|---|---|
Volumetric Scale/mL | |||||||||
1.8 1 | 6 | 21.9 | 36 | 42 | 138 | 6 | Freeze-Dried Powder | ||
DSC | Tg/°C | - | 59.3 ± 0.01 | 57.9 1 | 58.6 ± 1.0 2 | - | - | 71.6 1 | 47.7 ± 0.5 |
Td/°C | 35.7 | 39.1 ± 5.3 | 54.2 ± 15.9 | 43.5 ± 13.5 | 66.2 ± 2.8 | 67.5 ± 4.2 | 59.9 ± 0.3 | 60.7 ± 8.8 | |
∆Hd/J g−1 | −267.7 | −207.8 ± 98.0 | −197.5 ± 4.6 | −197.5 ± 30.1 | −211.8 ± 15.8 | −191.9 ± 8.9 | −191.8 ± 0.9 | −276.9 ± 4.21 | |
Tg’/°C | - | - | - | - | - | - | - | 184.5 ± 0.7 | |
Tc/°C | - | - | - | - | - | - | - | 241.0 ± 0.8 | |
∆Hc/J g−1 | - | - | - | - | - | - | - | 9.9 ± 2.3 | |
To/°C | 274.1 | 274.0 ± 0.3 | 273.4 ± 0.6 | 267.4 ± 1.7 | 267.8 ± 0.8 | 265.7 ± 1.5 | 264.4 ± 0.1 | - | |
Tdec/°C | 290.4 | 289.5 ± 0.5 | 289.5 ± 0.3 | 284.7 ± 0.4 | 284.9 ± 0.5 | 284.0 ± 1.0 | 282.1 ± 0.4 | 274.9 ± 1.1 1 | |
TGA | Water content/% (w/w) | 23.8 | 13.0 ± 1.7 | 11.7 ± 0.8 | 11.2 ± 0.7 | 10.7 ± 0.7 | 10.2 ± 0.6 | 5.2 ± 0.5 | 5.8 ± 0.8 |
To/°C | 278.8 | 277.3 ± 0.2 | 278.1 ± 1.0 | 272.3 ± 0.1 | 273.2 ± 0.6 | 271.5 ± 0.9 | 271.2 ± 0.5 | 198.5 ± 2.2 | |
To’/°C | - | - | - | - | - | - | - | 261.4 ± 2.0 | |
Tdec/°C | 289.7 | 299.6 ± 6.6 | 293.1 ± 4.1 | 299.0 ± 10.3 | 297.7 ± 5.5 | 298.1 ± 11.3 | 293.4 ± 5.8 | 222.3 ± 13.3 | |
Tdec’/°C | - | - | - | - | - | - | - | 275.0 ± 2.7 |
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Matthew, S.A.L.; Rezwan, R.; Perrie, Y.; Seib, F.P. Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods. Molecules 2022, 27, 2368. https://doi.org/10.3390/molecules27072368
Matthew SAL, Rezwan R, Perrie Y, Seib FP. Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods. Molecules. 2022; 27(7):2368. https://doi.org/10.3390/molecules27072368
Chicago/Turabian StyleMatthew, Saphia A. L., Refaya Rezwan, Yvonne Perrie, and F. Philipp Seib. 2022. "Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods" Molecules 27, no. 7: 2368. https://doi.org/10.3390/molecules27072368