# US 2026/0108730 A1 · Methods for modulating temporal infrastructure of pulsed electric fields

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- Number: US 2026/0108730 A1
- Document ID: US20260108730A1
- Status: Published application
- Kind: A1
- Application number: 19/368,292
- Filed: 2025-10-24
- Published: 2026-04-23
- Earliest claimed: 2020-11-25
- Assignees: Virginia Tech Intellectual Properties, Inc.
- Applicants: Virginia Tech Intellectual Properties, Inc.
- Inventors: Kenneth N. Aycock; Rafael V. Davalos
- Web page: https://patentgrep.com/patent/US20260108730A1

## CPC

- A61N 1/327: {for enhancing the absorption properties of tissue, e.g. by electroporation}
- A61N 1/0416: {Anode and cathode}
- A61B 18/1206: {Generators therefor}
- A61B 18/1477: {Needle-like probes}
- A61B 2018/00577: {Ablation}
- A61B 2018/00613: {Irreversible electroporation}
- A61B 2018/00726: {Duty cycle}
- A61B 2018/00761: {Duration}
- A61B 2018/1472: {for use with liquid electrolyte, e.g. virtual electrodes}
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

High-frequency irreversible electroporation (H-FIRE) is a tissue ablation modality employing bursts of electrical pulses in a positive phase-interphase delay-negative phase-interpulse delay pattern. Despite accumulating evidence suggesting the significance of these delays, their effects on therapeutic outcomes from clinically-relevant H-FIRE waveforms have not been studied extensively. The present invention provides methods of pulse delivery, including delays, that mitigate bubble formation and/or minimize the risk of arcing, such as due to the presence of bubbles, and/or minimize muscle stimulation are described herein.

## Claims

### Claim 1

A method of applying electrical energy to tissue, the method comprising:
administering to a tissue a series of bursts of bipolar electrical pulses, wherein each bipolar electrical pulse comprises a positive phase and a negative phase, wherein each phase has a duration of 250 ns to 250 μs, with or without a delay between the positive and negative phases;
wherein each bipolar electrical pulse is separated by a delay lasting up to 1 ms;
wherein the bipolar electrical pulses are repeated until a total energized time of 1 μs to 500 μs is achieved;
wherein one or more of the bursts has a burst width of at least 1 μs;
wherein the series of bursts is administered for a total time of 250 ms to 10 seconds; and
wherein the bipolar electrical pulses are applied at a voltage ranging from 500 V to 10 kV.

### Claim 2 (depends on 1)

The method of claim 1, wherein the series of bursts is administered in a manner to provide reversible electroporation or irreversible electroporation.

### Claim 3 (depends on 1)

The method of claim 1, wherein where cardiac synchronization is desired one or more of the bursts has a burst width of 10 μs to 300 ms.

### Claim 4 (depends on 1)

The method of claim 1, wherein each phase has a duration of 250 ns to 10 μs and wherein the bipolar electrical pulses are applied at a voltage ranging from 1 kV to 5 kV.

### Claim 5 (depends on 1)

The method of claim 1, wherein one or more of the bursts has a burst width of 100 μs.

### Claim 6 (depends on 1)

The method of claim 1, wherein there is a delay between one or more of the positive phases and the negative phase.

### Claim 7 (depends on 6)

The method of claim 6, wherein the delay between the positive phase and the negative phase is shorter than the delay between each bipolar electrical pulse.

### Claim 8

A method for applying electrical energy to tissue, the method comprising:
administering to a tissue a series of bursts of positive monopolar electrical pulses;
wherein each of the positive pulses has a duration of 250 ns to 250 μs;
wherein each burst comprises one or more delay of up to 100 ms;
wherein the positive pulses are repeated until a total energized time of 1 μs to 500 μs is achieved;
wherein the burst interval of at least two of the bursts is between 250 ms and 10 seconds;
and wherein the positive pulses are applied at a voltage ranging from 25 V to 10 kV.

### Claim 9 (depends on 8)

The method of claim 8, wherein the series of bursts is administered to provide reversible electroporation or irreversible electroporation.

### Claim 10 (depends on 8)

The method of claim 8, wherein the positive pulses are applied at a voltage ranging from 500 V to 5 kV.

### Claim 11 (depends on 8)

The method of claim 8, wherein the positive pulses each have a duration of 250 ns to 10 μs.

### Claim 12 (depends on 8)

The method of claim 8, wherein a burst is administered once every 0.5 s to 3 s.

### Claim 13 (depends on 8)

The method of claim 8, wherein at least one of the bursts has a burst width of 100 μs.

### Claim 14

A method of applying electrical energy to tissue, the method comprising:
applying one or more burst of a plurality of electrical pulses to a tissue;
wherein one or more of the bursts comprises energy with positive phases and/or negative phases;
wherein one or more parameters of the burst are selected such that the burst is capable of causing electroporation of the tissue in a manner that avoids, prevents, minimizes or suppresses neural excitation, bubble formation, and/or Joule heating.

### Claim 15 (depends on 14)

The method of claim 14, wherein one or more of the parameters is that a time between one of the pulses and another of the pulses is longer than a time between one of the positive phases and one of the negative phases.

### Claim 16 (depends on 14)

The method of claim 14, wherein the time between one of the positive phases and one of the negative phases comprises an interphase delay ranging from 0 to 5 μs.

### Claim 17 (depends on 14)

The method of claim 14, wherein the time between one of the electrical pulses and another of the electrical pulses comprises an interpulse delay in the range of 10 μs to 1 second.

### Claim 18 (depends on 17)

The method of claim 17, wherein the interpulse delay is 5 to 1,000 times longer than an interphase delay of the electrical pulses.

### Claim 19 (depends on 14)

The method of claim 14, wherein one or more of the bursts has a total energized time of from 1 μs to 1 s.

### Claim 20 (depends on 14)

The method of claim 14, wherein one or more of the pulses, one or more of the positive phases, and/or one or more of the negative phases have a length of up to 10 μs.
