Quantitative 3D reconstruction of porous polymers using FIB-SEM tomography -correlating materials structures to properties of coatings for controlled drug release
Doctoral thesis, 2020
In this work the focus is on the understanding of the correlation between the structure and materials properties of phase-separated polymer film coatings used for controlled drug release. We acquired high spatial 3D resolution data on microporous ethyl cellulose and hydroxypropyl cellulose film coatings using FIB-SEM tomography. The tomography was performed after the water soluble hydroxypropyl cellulose phase had been removed leaving a porous network providing a transport path for the drug. We optimised the FIB-SEM parameters and established a generic protocol for porous and poorly conducting materials in order to overcome challenges such as redeposition, curtaining, shadowing effects, charging and sub-surface information due to the pores. In addition, a new self-learning segmentation algorithm was introduced to enable an automatic separation between pores and matrix. The quantification of the porous network was carried out by determining the pore size distribution, tortuosity and interconnectivity. As a final step, diffusion simulations were performed on the FIB-SEM data and correlated with experimentally measured permeability.
scanning electron microscopy
focused ion beam
controlled drug release
Nano and Biophysics
C. Fager, M. Röding, A. Olsson, C. von Corswant, N. Lorén, A. Särkkä and E. Olsson. Optimisation of FIB-SEM tomography and reconstruction for soft, porous and poorly conducting materials
M. Röding, C. Fager, A. Olsson, C. von Corswant, A. Särkkä, E. Olsson and N. Lorén. Three-dimensional reconstruction of porous polymer films from FIB-SEM tomography data using random forests
C. Fager, S. E. Barman, M. Röding, A. Olsson, C. von Corswant, N. Lorén, H. Rotzén, D. Bolin and E. Olsson. 3D high spatial resolution visualisation and quantification of interconnectivity in polymer coatings
S. Barman, C. Fager, M. Röding, A. Olsson, C. von Corswant, N. Lorén, D. Bolin, E. Olsson and H. Rootzén. New characterization measures of pore shape and connectivity applied to polymer film coatings used for controlled drug release
C. Fager, J. Hjärtstam, T. Gebäck, M. Röding, C. von Corswant, A. Olsson, N. Lorén, A. Särkkä and E. Olsson. Correlating 3D porous structure with mass transport properties in polymer films using FIB-SEM tomography
C. Fager, C. von Corswant, A. Viridén, , M-O. Johansson, A. Olsson, M. Röding, N. Lorén, A. Särkkä and E. Olsson. Revealing the porous structure of pellet film coatings used for controlled drug release dosage forms
C. Fager, C. von Corswant, A. Olsson, M. Röding, T. Nilsson Pingel, N. Lorén, A. Särkkä, E. Olsson. Revealing regions with different transport characteristics in coatings for controlled drug release by 3D visualisation
The aim of this work was to develop a generic protocol for optimised FIB-SEM tomography for soft, porous and poorly conducting materials and to use the quantitative experimental data to simulate transport properties. The protocol was used for model porous polymer films and polymer film coated pellets representative of structures used for controlled drug release in pharmaceuticals. The 3D reconstruction and quantitative evaluation of the porous network provided information about important structural characteristics such as pore connectivity, tortuosity and geodesic paths. The structural information was used to simulate transport properties and explained the experimentally measured diffusion properties of different porous polymer films.
Material structures seen through microscopes and statistics
Swedish Foundation for Strategic Research (SSF), 2014-04-01 -- 2019-06-30.
Chalmers Materials Analysis Laboratory
Areas of Advance
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4768
Chalmers University of Technology
Nexus, Origo, level 4, Department of Physics, Chalmers University of Technology
Opponent: Prof. Ehrenfried Zschech, Department of Microelectronic Materials and Nanoanalysis, Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Germany