Projects / Programmes
Development and validation of a software for numerical modeling of in vivo electroporation - in silico electroporation
| Code |
Science |
Field |
Subfield |
| 2.06.07 |
Engineering sciences and technologies |
Systems and cybernetics |
Biomedical technics |
| Code |
Science |
Field |
| T115 |
Technological sciences |
Medical technology |
| Code |
Science |
Field |
| 2.06 |
Engineering and Technology |
Medical engineering
|
electroporation, computational models, finite element method, symbolic code generation, inverse analysis, effective conductivity, heat transfer, mass transfer, cell resealing, electrochemotherapy, food preservation, microbial inactivation, water treatment, tissue ablation, fluorescent dyes biologically active molecules
Researchers (19)
Organisations (3)
Abstract
Electroporation is a phenomenon where permeability of the cell membrane temporarily increases due to exposure of a cell to a high-intensity pulsed electric field. Currently, electroporation is used in numerous applications, such as electrochemotherapy of tumours, gene electrotransfer, non-thermal tissue ablation, food preservation, and wastewater treatment. In order to successfully perform electroporation, the electric field distribution around the target cells or tissue needs to be determined accurately. Because this is difficult to achieve experimentally, numerical modelling is often employed. However, current numerical models are mostly inadequate since they do not accurately describe the phenomena which occur during and after electroporation, such as the heat and mass transfer, and cell membrane resealing.
The aim of this project is to develop a comprehensive experimentally validated multi-physics computational model of electroporation, i.e. electroporation in silico. Development will consist of three stages. In the first stage, a non-linear model of electroporation will be developed and validated analytically and experimentally. This model will then be extended to a transient non-linear multi-physics model of electroporation, which will additionally include heat and mass transfer relevant to electroporation applications, namely heating of the biological sample and transport of molecules into cells and tissues. If the bigger project is funded, the model will be additionally improved with the inclusion of a special boundary condition for modelling thin layers, and with inclusion of a model of cell membrane resealing.
In the second stage, the extended transient non-linear multi-physics model of electroporation will be comprehensively validated in vitro, ex vivo and in vivo, to verify the predictions of the model and to provide the necessary data for extending the model for its use in development of existing and new electroporation based applications. Validation will include the measurements of voltage, electric current, temperature and mass transfer, at various pulse parameters (amplitude, pulse duration, repetition frequency and number of pulses) in vitro, ex vivo as well as in vivo. If the bigger project is funded, the additional validation will be performed with advanced analytical techniques in vitro and in vivo.
In the third stage, the electroporation model will be assembled in the application-specific finite element method software. The project will employ symbolic code generation to rapidly transfer the physics describing the electroporation model into a computationally efficient numerical application. Inverse analysis procedures will be implemented, which will allow efficient identification of currently unknown material properties of cells or tissues such as the change of effective conductivity due to electroporation. If the bigger project is funded, the specific finite element method software for modelling electroporation will be extended with a prototype framework for integration of all necessary software components. Additional graphical user interface for simulation setup and visualization of basic results will be implemented in this software.
The research performed within the project will contribute to a better understanding of the electroporation phenomenon and the associated processes. The finite element method based software and implemented electroporation models will also increase the accessibility of computational in silico electroporation, and the developed software will provide an efficient platform for computational experiments. This will be useful in different applications of electroporation, such as electrochemotherapy of tumours, gene electrotransfer, non-thermal tissue ablation, food preservation, and water treatment, to name a few.
Significance for science
An integrated in silico framework for research and optimization of electroporation based technologies and treatments has been developed. The in silico framework encompasses the development of realistic models, which enable the prediction of effects of in vivo electroporation and the development of accompanying software. The computer models have been successfully validated both ex vivo and in vivo, and the whole in silico framework has been successfully tested in a realistic environment encompassing biology, biotechnology and medicine. This shows, that the in silico framework has multiple beneficial effects on the development of science in the area of electroporation and beyond. The validated computer models of electroporation (realistic models) enable a more precise prediction of the effects of electroporation pulses in comparison to models that were used previously, since they are based on the detection of changes of electrical properties of tissue in dependence on electroporation. The newly developed electroporation models enable faster development and better treatment planning of difficult-to-treat diseases with e.g. electrochemotherapy, gene therapy with gene electrotransfer and tissue ablation with irreversible electroporation. The software framework built during the scope of the project will ease the use of electroporation models also for development of new applications, since it simplifies the use also for researchers from the field of biology, biotechnology and medicine. The software framework therefore represents an efficient framework for innovative computer experiments and enables the development of specialized tools. The validated computer models of electroporation will significantly enhance research in the area of electroporation and further the expansion of the field itself, while simultaneously improving the effectiveness and success of applications based on electroporation. The newly developed electroporation models are already used for guiding new experiments, while shortening development cycles and reducing costs associated with the development of novel application. They enable researchers to improve the time- and cost-effectiveness of new experiments in the area. The validated computer models of electroporation also present a framework for new basic research and can yield key parameters that need to be determined before migrating the technology to new tissues or cell lines. The improved and validated models of electroporation also reduce the need for animal experiments, since the most important parameters of the model are already determined.
Significance for the country
The results of the present research project and the in silico computational framework have solidified the position of Slovenia as one of the leading countries in the area of electroporation research. Our results directly contribute to a better understanding of the use of electroporation in the area of clinical medicine using tools such as electrochemotherapy and gene therapy leading to a greater acceptance of these technologies in the Slovenian and international clinical environment. The knowledge gained in the research project has already been included in the teaching process at the University of Ljubljana both in the scope of Masters’ and PhD level studies. One example is the yearly Electroporation-based Technologies and Treatments which has been attended by more than 100 PhD students from more than 19 countries. The results have been presented at Slovenian and international conferences and published in numerous SCI-indexed scientific journals, which is of exceptional importance to the recognition of Republic of Slovenia in the international scientific community. The co-financing small enterprise C3M sees the research project as a well utilised opportunity to enter the market of medical device software. The company estimates that the entry to the market had a direct positive effect (10-15 %) on the size of the company’s software and IT consulting division. The knowledge and experience, that the company has gained through the project will also be usefully utilised in other segments of the company’s market. The tools that have been developed in the course of the project enable C3M’s ability to support the industry with development
Most important scientific results
Annual report
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2011,
2012,
2013,
final report,
complete report on dLib.si
