The Experts below are selected from a list of 63693 Experts worldwide ranked by ideXlab platform
Boris Rubinsky - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous Electroporation and dielectrophoresis in non-electrolytic micro/nano-Electroporation
Scientific reports, 2018Co-Authors: Chenang Lyu, Jianping Wang, Matthew J. Powell-palm, Boris RubinskyAbstract:It was recently shown that electrolysis may play a substantial detrimental role in microfluidic Electroporation. To overcome this problem, we have developed a non-electrolytic micro/nano Electroporation (NEME) electrode surface, in which the metal electrodes are coated with a dielectric. A COMSOL based numerical scheme was used to simultaneously calculate the excitation frequency and dielectric material properties dependent electric field delivered across the dielectric, fluid flow, Electroporation field and Clausius-Mossotti factor for yeast and E. coli cells flowing in a channel flow across a NEME surface. A two-layer model for yeast and a three-layer model for E. coli was used. The numerical analysis shows that in NEME Electroporation, the electric fields could induce Electroporation and dielectrophoresis simultaneously. The simultaneous occurrence of Electroporation and dielectrophoresis gives rise to several interesting phenomena. For example, we found that a certain frequency exists for which an intact yeast cell is drawn to the NEME electrode, and once electroporated, the yeast cell is pushed back in the bulk fluid. The results suggest that developing Electroporation technologies that combine, simultaneously, Electroporation and dielectrophoresis could lead to new applications. Obviously, this is an early stage numerical study and much more theoretical and experimental research is needed.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: BACKGROUND: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study, we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). METHOD: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW) was applied to the pig liver, and the effect of various parameters on the extent of tissue ablation was examined with histology. RESULTS: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue. DISCUSSION: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Background: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). Method: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW), was applied to the pig liver and the effect of various parameters on the extent of tissue ablation was examined with histology. Results: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue Discussion: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Electrolytic Effects During Tissue Ablation by Electroporation
Technology in Cancer Research & Treatment, 2016Co-Authors: Liel Rubinsky, Enric Guenther, Paul Mikus, Michael K. Stehling, Boris RubinskyAbstract:Nonthermal irreversible Electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible Electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with Electroporation pulses to augment and optimize tissue ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible Electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible Electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible Electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that tissue ablation ascribed in the past to irreversible Electroporation is actually caused by at least 3 different cytotoxic effects: irreversible Electroporation without electrolysis, irreversible Electroporation combined with electrolysis, and reversible Electroporation combined with electrolysis. These different mechanisms may affect cell and tissue ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of Electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible Electroporation studies in tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal Electroporation ablation protocols.
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Synergistic combination of electrolysis and Electroporation for tissue ablation
PLOS ONE, 2016Co-Authors: Michael K. Stehling, Liel Rubinsky, Enric Guenther, Paul Mikus, Nina Klein, Boris RubinskyAbstract:Electrolysis, electrochemotherapy with reversible Electroporation, nanosecond pulsed electric fields and irreversible Electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and Electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible Electroporation magnitude pulses, designed in such a way that the charge delivered during the Electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude Electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible Electroporation and nanosecond pulsed ablation.
Damijan Miklavčič - One of the best experts on this subject based on the ideXlab platform.
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In vitro Electroporation detection methods - An overview.
Bioelectrochemistry (Amsterdam Netherlands), 2017Co-Authors: Tina Batista Napotnik, Damijan MiklavčičAbstract:Exposing cells to an electric field leads to Electroporation of the cell membrane which has already been explored and used in a number of applications in medicine and food biotechnology (e.g. electrochemotherapy, gene electrotransfer, extraction of biomolecules). The extent of Electroporation depends on several conditions, including pulse parameters, types of cells and tissues, surrounding media, temperature etc. Each application requires a specific level of Electroporation, so it must be explored in advance by employing methods for detecting Electroporation. Electroporation detection is most often done by measuring increased transport of molecules across the membrane, into or out of the cell. We review here various methods of Electroporation detection, together with their advantages and disadvantages. Electroporation detection can be carried out by using dyes (fluorophores or colour stains) or functional molecules, by measuring the efflux of biomolecules, by impedance measurements and voltage clamp techniques as well as by monitoring cell swelling. This review describes methods of detecting cell membrane Electroporation in order to help researchers choose the most suitable ones for their specific experiments, considering available equipment and experimental conditions.
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tutorial Electroporation of cells in complex materials and tissue
Journal of Applied Physics, 2016Co-Authors: Lea Rems, Damijan MiklavčičAbstract:Electroporation is being successfully used in biology, medicine, food processing, and biotechnology, and in some environmental applications. Recent applications also include in addition to classical Electroporation, where cells are exposed to micro- or milliseconds long pulses, exposures to extremely short nanosecond pulses, i.e., high-frequency Electroporation. Electric pulses are applied to cells in different structural configurations ranging from suspended cells to cells in tissues. Understanding Electroporation of cells in tissues and other complex environments is a key to its successful use and optimization in various applications. Thus, explanation will be provided theoretically/numerically with relation to experimental observations by scaling our understanding of Electroporation from the molecular level of the cell membrane up to the tissue level.
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Electroporation based applications in biotechnology
Trends in Biotechnology, 2015Co-Authors: Tadej Kotnik, Wolfgang Frey, Martin Sack, Sasa Haberl Meglic, Matjaž Peterka, Damijan MiklavčičAbstract:Electroporation is already an established technique in several areas of medicine, but many of its biotechnological applications have only started to emerge; we review here some of the most promising. We outline Electroporation as a phenomenon and then proceed to applications, first outlining the best established – the use of reversible Electroporation for heritable genetic modification of microorganisms (electrotransformation), and then explore recent advances in applying Electroporation for inactivation of microorganisms, extraction of biomolecules, and fast drying of biomass. Although these applications often aim to upscale to the industrial and/or clinical level, we also outline some important chip-scale applications of Electroporation. We conclude our review with a discussion of the main challenges and future perspectives.
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Electroporation-based applications in biotechnology.
Trends in biotechnology, 2015Co-Authors: Tadej Kotnik, Wolfgang Frey, Martin Sack, Sasa Haberl Meglic, Matjaž Peterka, Damijan MiklavčičAbstract:Electroporation is already an established technique in several areas of medicine, but many of its biotechnological applications have only started to emerge; we review here some of the most promising. We outline Electroporation as a phenomenon and then proceed to applications, first outlining the best established – the use of reversible Electroporation for heritable genetic modification of microorganisms (electrotransformation), and then explore recent advances in applying Electroporation for inactivation of microorganisms, extraction of biomolecules, and fast drying of biomass. Although these applications often aim to upscale to the industrial and/or clinical level, we also outline some important chip-scale applications of Electroporation. We conclude our review with a discussion of the main challenges and future perspectives.
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Electroporation based technologies for medicine principles applications and challenges
Annual Review of Biomedical Engineering, 2014Co-Authors: Martin L Yarmush, Alexander Golberg, Gregor Sersa, Tadej Kotnik, Damijan MiklavčičAbstract:When high-amplitude, short-duration pulsed electric fields are applied to cells and tissues, the permeability of the cell membranes and tissue is increased. This increase in permeability is currently explained by the temporary appearance of aqueous pores within the cell membrane, a phenomenon termed Electroporation. During the past four decades, advances in fundamental and experimental Electroporation research have allowed for the translation of Electroporation-based technologies to the clinic. In this review, we describe the theory and current applications of Electroporation in medicine and then discuss current challenges in Electroporation research and barriers to a more extensive spread of these clinical applications.
Michael K. Stehling - One of the best experts on this subject based on the ideXlab platform.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: BACKGROUND: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study, we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). METHOD: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW) was applied to the pig liver, and the effect of various parameters on the extent of tissue ablation was examined with histology. RESULTS: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue. DISCUSSION: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Background: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). Method: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW), was applied to the pig liver and the effect of various parameters on the extent of tissue ablation was examined with histology. Results: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue Discussion: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Electrolytic Effects During Tissue Ablation by Electroporation
Technology in Cancer Research & Treatment, 2016Co-Authors: Liel Rubinsky, Enric Guenther, Paul Mikus, Michael K. Stehling, Boris RubinskyAbstract:Nonthermal irreversible Electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible Electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with Electroporation pulses to augment and optimize tissue ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible Electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible Electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible Electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that tissue ablation ascribed in the past to irreversible Electroporation is actually caused by at least 3 different cytotoxic effects: irreversible Electroporation without electrolysis, irreversible Electroporation combined with electrolysis, and reversible Electroporation combined with electrolysis. These different mechanisms may affect cell and tissue ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of Electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible Electroporation studies in tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal Electroporation ablation protocols.
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Synergistic combination of electrolysis and Electroporation for tissue ablation
PLOS ONE, 2016Co-Authors: Michael K. Stehling, Liel Rubinsky, Enric Guenther, Paul Mikus, Nina Klein, Boris RubinskyAbstract:Electrolysis, electrochemotherapy with reversible Electroporation, nanosecond pulsed electric fields and irreversible Electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and Electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible Electroporation magnitude pulses, designed in such a way that the charge delivered during the Electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude Electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible Electroporation and nanosecond pulsed ablation.
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Minimally Invasive, Non-Thermal Tissue Ablation with a Single Exponential Decay Electrolytic Electroporation Waveform
Journal of Translational Medicine and Research, 2016Co-Authors: Boris Rubinsky, Paul Mikus, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Enric Gunther, Vlad Herlea, Catalin Pecheanu, Michael K. StehlingAbstract:A new minimally invasive tissue ablation technique, that combines the biophysical processes of Electroporation and electrolysis, is introduced. The technology employs electrode needles inserted in the target tissue to deliver an Electrolytic Electroporation Waveform (EEW) in the form of an exponential decay voltage, several tens of microsecond long. A case study in a large animal model demonstrates that clinically significant size lesions can be achieved with a single, milliseconds long EEW. Ablation with EEW has major advantages over the comparable tissue ablation techniques of electrolysis, reversible Electroporation and irreversible Electroporation. EEW is orders of magnitude faster than conventional electrolytic ablation. EEW does not require the use of muscle relaxant as irreversible Electroporation and EEW does not require injection of drugs as reversible Electroporation. This new technology is simple to use and may become an important addition to the minimally invasive surgery armamentarium.
Nina Klein - One of the best experts on this subject based on the ideXlab platform.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: BACKGROUND: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study, we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). METHOD: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW) was applied to the pig liver, and the effect of various parameters on the extent of tissue ablation was examined with histology. RESULTS: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue. DISCUSSION: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Background: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). Method: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW), was applied to the pig liver and the effect of various parameters on the extent of tissue ablation was examined with histology. Results: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue Discussion: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Synergistic combination of electrolysis and Electroporation for tissue ablation
PLOS ONE, 2016Co-Authors: Michael K. Stehling, Liel Rubinsky, Enric Guenther, Paul Mikus, Nina Klein, Boris RubinskyAbstract:Electrolysis, electrochemotherapy with reversible Electroporation, nanosecond pulsed electric fields and irreversible Electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and Electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible Electroporation magnitude pulses, designed in such a way that the charge delivered during the Electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude Electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible Electroporation and nanosecond pulsed ablation.
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Minimally Invasive, Non-Thermal Tissue Ablation with a Single Exponential Decay Electrolytic Electroporation Waveform
Journal of Translational Medicine and Research, 2016Co-Authors: Boris Rubinsky, Paul Mikus, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Enric Gunther, Vlad Herlea, Catalin Pecheanu, Michael K. StehlingAbstract:A new minimally invasive tissue ablation technique, that combines the biophysical processes of Electroporation and electrolysis, is introduced. The technology employs electrode needles inserted in the target tissue to deliver an Electrolytic Electroporation Waveform (EEW) in the form of an exponential decay voltage, several tens of microsecond long. A case study in a large animal model demonstrates that clinically significant size lesions can be achieved with a single, milliseconds long EEW. Ablation with EEW has major advantages over the comparable tissue ablation techniques of electrolysis, reversible Electroporation and irreversible Electroporation. EEW is orders of magnitude faster than conventional electrolytic ablation. EEW does not require the use of muscle relaxant as irreversible Electroporation and EEW does not require injection of drugs as reversible Electroporation. This new technology is simple to use and may become an important addition to the minimally invasive surgery armamentarium.
Paul Mikus - One of the best experts on this subject based on the ideXlab platform.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: BACKGROUND: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study, we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). METHOD: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW) was applied to the pig liver, and the effect of various parameters on the extent of tissue ablation was examined with histology. RESULTS: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue. DISCUSSION: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Single exponential decay waveform; a synergistic combination of Electroporation and electrolysis (E2) for tissue ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Background: Electrolytic ablation and Electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of Electroporation and electrolysis (E2). Method: A new device that delivers a controlled dose of Electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW), was applied to the pig liver and the effect of various parameters on the extent of tissue ablation was examined with histology. Results: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in Electroporation or electrolysis separately, cannot ablate the tissue Discussion: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible Electroporation with injection of drugs) and irreversible Electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and Electroporation, without the need to inject drugs as in reversible Electroporation or use paralyzing anesthesia as in irreversible Electroporation.
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Electrolytic Effects During Tissue Ablation by Electroporation
Technology in Cancer Research & Treatment, 2016Co-Authors: Liel Rubinsky, Enric Guenther, Paul Mikus, Michael K. Stehling, Boris RubinskyAbstract:Nonthermal irreversible Electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible Electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with Electroporation pulses to augment and optimize tissue ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible Electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible Electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible Electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that tissue ablation ascribed in the past to irreversible Electroporation is actually caused by at least 3 different cytotoxic effects: irreversible Electroporation without electrolysis, irreversible Electroporation combined with electrolysis, and reversible Electroporation combined with electrolysis. These different mechanisms may affect cell and tissue ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of Electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible Electroporation studies in tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal Electroporation ablation protocols.
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Synergistic combination of electrolysis and Electroporation for tissue ablation
PLOS ONE, 2016Co-Authors: Michael K. Stehling, Liel Rubinsky, Enric Guenther, Paul Mikus, Nina Klein, Boris RubinskyAbstract:Electrolysis, electrochemotherapy with reversible Electroporation, nanosecond pulsed electric fields and irreversible Electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and Electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible Electroporation magnitude pulses, designed in such a way that the charge delivered during the Electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude Electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible Electroporation and nanosecond pulsed ablation.
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Minimally Invasive, Non-Thermal Tissue Ablation with a Single Exponential Decay Electrolytic Electroporation Waveform
Journal of Translational Medicine and Research, 2016Co-Authors: Boris Rubinsky, Paul Mikus, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Enric Gunther, Vlad Herlea, Catalin Pecheanu, Michael K. StehlingAbstract:A new minimally invasive tissue ablation technique, that combines the biophysical processes of Electroporation and electrolysis, is introduced. The technology employs electrode needles inserted in the target tissue to deliver an Electrolytic Electroporation Waveform (EEW) in the form of an exponential decay voltage, several tens of microsecond long. A case study in a large animal model demonstrates that clinically significant size lesions can be achieved with a single, milliseconds long EEW. Ablation with EEW has major advantages over the comparable tissue ablation techniques of electrolysis, reversible Electroporation and irreversible Electroporation. EEW is orders of magnitude faster than conventional electrolytic ablation. EEW does not require the use of muscle relaxant as irreversible Electroporation and EEW does not require injection of drugs as reversible Electroporation. This new technology is simple to use and may become an important addition to the minimally invasive surgery armamentarium.