Projects / Programmes
Cellular Electrical Engineering
January 1, 2004
- December 31, 2008
| Code |
Science |
Field |
Subfield |
| 2.06.00 |
Engineering sciences and technologies |
Systems and cybernetics |
|
| 1.02.00 |
Natural sciences and mathematics |
Physics |
|
| Code |
Science |
Field |
| T190 |
Technological sciences |
Electrical engineering |
electroporation, electropermeabilization, neoplasms, gene therapy, finite elements method, electrodes, medical devices, electrotherapy, electrocardiogram, blood flow and tumor oxygenation, biological signals, signal processing, water sterilization
Researchers (26)
Organisations (1)
Abstract
An exposure of a cell to an electric field of an adequate strength and duration leads to a transient increase of cell membrane permeability. This phenomenon, termed electroporation or electropermeabilization, allows various otherwise nonpermeant molecules to cross the membrane and enter the cell. Both in vitro and in vivo, reversible electroporation allows for internalization of a wide range of substances, including chemotherapeutics and DNA.
A combination of electroporation and a chemotherapeutic drug, termed electrochemotherapy, leads to a significant increase of the antitumor effect of the drug. The Cliniporator device, developed in our laboratory in collaboration with partners from France, Germany, Italy, Denmark and Belgium within the 5th EU framework, is currently efficient for treatment of cutaneous and subcutaneous tumors. To allow for treatment of the tumors deeper in the body, either during surgery or with endoscopic electrodes, we are developing a system for synchronization of the pulses with the ECG signal. This system, which will be a component of the future generation of clinical electroporation devices, is being tested in collaboration with the Institute of Oncology in Ljubljana.
We are also involved in the development of standard procedures for clinical electrochemotherapy. We have developed a database and a web-based medical record system for clinical trials of electrochemotherapy with the purpose of accelerating the establishment of the therapy and the experience sharing among the medical centers in Europe.
Electroporation also provides a reliable nonviral method of DNA internalization. This method, termed electrogene transfection, is characterized by a stable gene expression in vivo, and thereby represents a safer alternative to viral vectors. The efficiency of the method is enhanced if short high-voltage pulses, which cause electroporation, are followed by longer pulses with lower voltage, which generate an electrophoretic driving force for the entry of DNA molecules into the cell. The Cliniporator device incorporates this option, and it is being evaluated on experimental animals.
The pulses used in electroporation influence the blood flow and oxygenation of the porated region of the tissue. We are studying these effects and their influence on the efficiency of electrochemotherapy and electrogene therapy in cooperation with the Institute of Oncology in Ljubljana.
For optimized efficiency of electroporation, it is advantageous if the ongoing process can be monitored in real time. During electroporation, electrical conductivity of a tissue or a dense cell suspension increases by several percent, the exact value being dependent on the conductivity of the extracellular substance and the volume fraction occupied by the cells. The electroporation devices able to adjust the pulse parameters based on such monitoring will represent a significant technological improvement to the current state of the art.
Irreversible electroporation can be used for water sterilization and nonthermal preservation of liquid food. By combining various methods of water sterilization (chlorination, heating or UV light) and electroporation, the effect is enhanced, and the concentrations of the chemical additives can be reduced, thus reducing the pollution of the environment.
Another important field of investigation is the development of models of field and current distribution in tissues exposed to electric pulses. These models are helpful in treatment planning (choice of electrodes and their positioning), in electrochemotherapy with the aim of efficient treatment of the whole tumor, and in electrogene therapy for poration of the largest possible volume without exceeding the irreversible threshold. In the development of these models we take into account the three-dimensional geometry of the electrodes and the tissues, as well as the changes in electrical properties of the tissue due to both membrane electroporation and heating...
Significance for science
The research programme addressed some of the important scientific and technological chalenges, including development of new cancer treatments and nonviral gene delivery for gene therapy of acquired and inherited diseases. These topics can also be found on the agenda of EU and other relevant international authorities. The use of electroporation in electrochemotherapy has already become an established method of cancer treatment, and in the opinion of many experts electroporation as a nonviral approach in gene delivery also holds great promises for improvement over viral gene transfection methods. One of the major goals of the programme was to improve electroporation efficiency by developing adequate instrumentation and protocols. In developing new electropoation based technologies and treatments, particularly electrochemotherapy and electrogene therapy, a substantial amount of new knowledge was obtained, providing both broader and deeper understanding of electroporation from the cell membrane to tissue level.
Significance for the country
The results obtained within the programme allow for introduction of numerous new methods, procedures and treatments into Slovenian scientific, academic and enterprise areas. Comprehensive development of instrumentation and methodologies also offered opportunities for training of students and researchers, including state-of-the-art expertise in the field of electroporation, as well as many other "collateral" positive effects in the socio-economic development. Since the research group is internationally well connected, this cooperation has also allowed for extensive exchange of our student and research personnel, resulting in transfer of knowledge and experience with equipment currently unavailable in Slovenia. The research group is gender balanced and offers equal opportunities to everyone.
Most important scientific results
Final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Final report,
complete report on dLib.si
