Quantitative 3D reconstruction of porous polymers using FIB-SEM tomography -correlating materials structures to properties of coatings for controlled drug release
Doktorsavhandling, 2020

Porous networks are found in a wide range of different advanced and technologically important materials and influence the materials properties. The networks are active components in for example batteries, food and pharmaceuticals. The interconnectivity of a network strongly influences the transport properties. One example is polymer film coatings for controlled drug release where the porous network acts as a transport path for drugs. The correlation between the detailed structure of the network and the transport properties illustrates the importance of quantifying the interconnectivity in 3D. One approach to image material in 3D is sequential imaging (tomography). Examples of tomography techniques are confocal laser scanning microscopy, x-ray and neutron tomography where the spatial resolution is limited to the micrometre length scale. Transmission electron microscopy tomography and focused ion beam (FIB) combined scanning electron microscope (SEM) tomography are examples of techniques with higher spatial resolution ranging from micrometre to sub-nanometre.

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.

polymer film

scanning electron microscopy

focused ion beam

3D

insulating material

soft material

connectivity

controlled drug release

tomography

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

Författare

Cecilia Fager

Nano- och biofysik

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

Understanding the correlation between materials structures and properties enables the optimisation of materials and tailoring them for specific applications. This work concerns porous networks in polymer coatings and in particular films for controlled drug release. The porous networks act as transport paths for drugs. To tailor the drug release, the correlation between the porous network and the transport properties is crucial. The network needs to be characterised in three dimensions (3D) and high spatial resolution 3D data can be acquired using a focused ion beam combined with scanning electron microscope (FIB-SEM) tomography. The FIB-SEM utilises an ion beam to perform serial sectioning and the electron beam to image the cross-section surface.

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.

Materialstrukturer genom mikroskop och statistik

Stiftelsen för Strategisk forskning (SSF), 2014-04-01 -- 2019-06-30.

Drivkrafter

Hållbar utveckling

Ämneskategorier

Materialteknik

Fysik

Infrastruktur

Chalmers materialanalyslaboratorium

Styrkeområden

Materialvetenskap

ISBN

978-91-7905-301-7

Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4768

Utgivare

Chalmers tekniska högskola

Nexus, Origo, level 4, Department of Physics, Chalmers University of Technology

Online

Opponent: Prof. Ehrenfried Zschech, Department of Microelectronic Materials and Nanoanalysis, Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Germany

Mer information

Senast uppdaterat

2020-05-19