Volumetric scalability of microfluidic and semi-batch silk nanoprecipitation methods

Saphia A. L. Matthew, Refaya Rezwan, Yvonne Perrie, F. Philipp Seib

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
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Abstract

Silk fibroin nanoprecipitation by organic desolvation in semi-batch and microfluidic formats provides promising bottom-up routes for manufacturing narrow polydispersity, spherical silk nanoparticles. The translation of silk nanoparticle production to pilot, clinical, and industrial scales can be aided through insight into the property drifts incited by nanoprecipitation scale-up and the identification of critical process parameters to maintain throughout scaling. Here, we report the reproducibility of silk nanoprecipitation on volumetric scale-up in low-shear, semi-batch systems and estimate the reproducibility of chip parallelization for volumetric scale-up in a high shear, staggered herringbone micromixer. We showed that silk precursor feeds processed in an unstirred semi-batch system (mixing time > 120 s) displayed significant changes in the nanoparticle physicochemical and crystalline properties following a 12-fold increase in volumetric scale between 1.8 and 21.9 mL while the physicochemical properties stayed constant following a further 6-fold increase in scale to 138 mL. The nanoparticle physicochemical properties showed greater reproducibility after a 6-fold volumetric scale-up when using lower mixing times of greater similarity (8.4 s and 29.4 s) with active stirring at 400 rpm, indicating that the bulk mixing time and average shear rate should be maintained during volumetric scale-up. Conversely, microfluidic manufacture showed high between-batch repeatability and between-chip reproducibility across four participants and microfluidic chips, thereby strengthening chip parallelization as a production strategy for silk nanoparticles at pilot, clinical, and industrial scales.
Original languageEnglish
Article number2368
Number of pages27
JournalMolecules
Volume27
Issue number7
Early online date6 Apr 2022
DOIs
Publication statusPublished - 6 Apr 2022

Funding

Acknowledgments: The authors thank Andrea Ducci (University College London, England, UK), Nigel Mottram (University of Glasgow, Scotland, UK), Alice Turner, Deborah Bowering, and Maider Olasolo (University of Strathclyde, Scotland, UK) for providing training and technical advice. The authors acknowledge that this work was carried out in part at the EPSRC Future Manufacturing Research Hub for Continuous Manufacturing and Advanced Crystallisation (CMAC) (EP/P006965/1) and was supported by a UK Research Partnership Fund award from the Higher Education Funding Council for England (Grant HH13054). The authors acknowledge that the electron scanning microscopy work was carried out at the Advanced Materials Research Laboratory, housed within the University of Strathclyde. This research was funded by Medical Research Scotland, PhD-1292-2018. We acknowledge the Engineering and Physical Sciences Research Council (EPSRC) funding EP/V034995/1 to establish the Thermal Equipment Suite. We thank the EPSRC Future Manufacturing Research Hub for Continuous Manufacturing and Advanced Crystallisation (CMAC) (EP/P006965/1) for support.

Keywords

  • silk fibroin
  • nanoprecipitation
  • semi-batch
  • microfluidics
  • scalable manufacture

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