Old Dominion University Research Foundation

Andrei G Pakhomov

Olga N Pakhomova

Shu Xiao

Karl H Schoenbach

Juergen Friedrich Kolb

Christian W Zemlin

Maura Casciola

Claudia Muratori

Ravindra Joshi

Olga N Pakhomov

Provided herein are methods of generating a biologically effective unipolar nanosecond electric pulse by superposing two biologically ineffective bipolar nanosecond electric pulses and related aspects, such as electroporation and/or therapeutic applications of these methods to non-invasively target electrostimulation (ES) selectively to deep tissues and organs.

Targeted remote electrostimulation by interference of bipolar nanosecond pulses

Systems and methods of enhancing membrane permeabilization in a cell are provided. An example method includes disposing the cell between a first electrode and a second electrode and applying a plurality of electrical pulses between the first electrode and the second electrode. In the systems and methods, the plurality of electrical pulses include at least two trains of pulses separated by an interval greater than about 10 s. Further, the amplitude of the electrical pulses is selected to be greater than about 0.2 kV/cm.

Electroporation-induced electrosensitization

Methods and apparatuses (systems, devices, etc.) for treating biological tissue to evoke one or more desirable biological and/or physiological effects using pulsed electric fields in the sub-microsecond range at very low electric field strength (e.g., less than 1 kV/cm) but at high (e.g., megahertz) frequencies.

Megahertz compression of nanosecond pulse bursts

Methods of enhancing membrane permeabilization in a cell are provided. A method includes disposing the cell between a first electrode and a second electrode and applying a plurality of electrical pulses between the first electrode and the second electrode. In the method, the plurality of electrical pulses include at least two trains of pulses separated by an interval greater than about 10 s. Further, the amplitude of the electrical pulses is selected to be greater than about 0.2 kV/cm.

The methods disclosed herein are directed towards improving ablation efficiency associated with applying nanosecond electric pulses (nsEP) to tissue. In particular, applying nsEP to tissue can open pores in the cellular membranes of the tissue. These pores can be kept open longer by cooling the tissue. The combined application of nsEP and the cooling of tissue may have synergistic effects on triggering apoptosis of cells in the tissue. This allows for numerous practical benefits associated with nsEP-based tissue ablation to be realized. For instance, nsEP of lower pulse strength or lower numbers of pulses to be used, which can be provided by smaller pulse generators operating on less power.

Methods and devices for using sub-microsecond electric pulses to trigger apoptosis

Methods for terminating fibrillation in a fibrillating heart employing nanosecond pulsed electric fields (nsPEFs) are disclosed. nsPEF defibrillation demonstrates its effectiveness as a new defibrillation modality, achieving reliable defibrillation with energies that are an order of magnitude lower than those needed for conventional defibrillation (millisecond shocks with mono- and bi-phasic waveforms). Tests did not reveal any negative effect of nsPEF defibrillation on cardiac tissue, in particular, cardiac tissue treated with nsPEFs does not exhibit a baseline shift in the optical transmembrane potential signal (distinctive feature that indicates electroporation), or changes in action potential duration or shape. The mechanism of nsPEF defibrillation is likely different from conventional defibrillation since it does not rely on membrane charging but on the basis of displacement currents that flow within nanoseconds after the shock is applied. nsPEFs provide the technology for the next generation of defibrillators that help emergency medical services to treat patients effectively.

Low-energy defibrillation with nanosecond pulsed electric fields

A system for treatment of biological tissues is provided. The system can deliver electric pulses to a targeted region within a biological tissue. The system includes an antenna assembly and a lens. The antenna assembly is configured to generate and direct electromagnetic radiation. The lens is configured to be positioned between a surface of the biological tissue and the antenna assembly. The lens can have a plurality of lossy portions. The lens can be configured to be adjustable to create a patient-specific desired electric field distribution by selective positioning of the plurality of lossy portions within the lens.

Treatment of biological tissues using subnanosecond electric pulses

A system for treatment of biological tissues is provided. The system includes a lens having a hollow, substantially hemispherical shape with an outer surface and an inner surface, the inner surface defining a substantially hemispherical cavity for inserting the biological tissues. The system further includes an antenna assembly for generating and directing electromagnetic radiation towards the outer surface. In the system, the lens is configured to direct the electromagnetic energy to an area in the cavity, a dielectric constant of the lens at the inner surface substantially matches a dielectric constant of the biological tissues, the dielectric constant monotonically increases from the outer surface to the inner surface, and the electromagnetic energy is generated via a series of pulses having a transient of less than about 1 nanosecond.

A system for producing maximal, but reversible bioeffects, for neuromuscular disruption. Methods for facilitation of neuromuscular functions in diseases and conditions of decreased excitability are provided.

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Norfolk, VA, United States of America

Andrei G Pakhomov