Pulsed Electric Field Electromanipulation for Targeted Tissue Ablation

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Solution Overview

Problem

Current methods for treating cancer using hyperthermia and electroporation are limited in their ability to independently control thermal and electrical effects, particularly in biological tissues, and have shown limited efficacy in enhancing the uptake of pharmacological agents or ablation of cells, especially when applied to tissues adjacent to healthy tissues.

Innovation Solution

A system and method that combines non-ionizing radiation to elevate tissue temperature with a pre-defined sequence of short voltage pulses to generate an electric field, ensuring electromanipulation without excessive temperature increase, allowing for the targeted delivery of pharmacological agents and enhanced ablation of unwanted tissues while minimizing damage to healthy tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If hyperthermia treatment is applied to elevate tissue temperature for cancer treatment, then thermal effects on target tissues are improved, but temperature control becomes difficult when combining with electrical pulses

Engineering Contradiction:
Improvetissue temperatureVSAvoidtemperature control
Core Design Contradiction:
TemperatureVSDevice complexity

Solution Approach 1:

The system applies electrical pulses before hyperthermia treatment to create electroporation in cell membranes, which facilitates subsequent drug delivery. This preliminary action allows the electrical component to prepare the tissue for thermal treatment without interfering with temperature control during the thermal phase.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The treatment is divided into separate temporal phases: an initial electrical pulse phase followed by a thermal hyperthermia phase. This segmentation allows independent optimization of each modality's parameters without mutual interference, resolving the temperature control difficulty when combining both effects.

Inventive Principle:
Principle #1Segmentation

2Quantity of substance

If electroporation is applied to enhance drug uptake in cells, then pharmacological agent delivery is improved, but thermal energy delivery becomes less effective when applied simultaneously

Engineering Contradiction:
Improvepharmacological agent uptakeVSAvoidthermal energy delivery
Core Design Contradiction:
Quantity of substanceVSUse of energy by moving object

Solution Approach 1:

Electroporation is applied as a preliminary step to create membrane permeability, followed by pharmacological agent administration. This sequence maximizes drug uptake while allowing thermal energy to be delivered subsequently for ablation without the interfering effect of simultaneous application.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The treatment uses periodic pulsed electric fields to induce electroporation, followed by periodic thermal cycles for hyperthermia. This periodic application in sequence allows both mechanisms to function optimally at different time intervals rather than competing simultaneously.

Inventive Principle:
Principle #19Periodic action

3Adaptability or versatility

If short voltage pulses are applied to induce electroporation, then cell membrane permeability is improved, but temperature elevation becomes excessive when combined with thermal therapy

Engineering Contradiction:
Improvecell membrane permeabilityVSAvoidtissue temperature
Core Design Contradiction:
Adaptability or versatilityVSTemperature

Solution Approach 1:

The electrical pulse delivery and thermal therapy are segmented into separate time intervals. Electrical pulses are delivered first to achieve membrane permeability, then thermal therapy is applied for controlled temperature elevation, preventing excessive temperature spikes that would occur with simultaneous application.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Electrical pulses are delivered as a preliminary action to establish membrane permeability before thermal therapy begins. This allows the subsequent thermal treatment to elevate temperature controllably without the confounding effect of simultaneous electrical heating from pulse delivery.

Inventive Principle:
Principle #10Preliminary action

4Reliability

If hyperthermia and electroporation are applied simultaneously to target tissues, then treatment effectiveness is improved, but damage to adjacent healthy tissues increases

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidhealthy tissue damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The simultaneous application is segmented into sequential phases: electrical pulses first to create selective membrane permeability in target cells, then thermal therapy to selectively ablate those same cells. This temporal segmentation maintains treatment effectiveness while reducing collateral damage to healthy tissues through controlled, staged delivery.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP2793995B1Electromanipulation of cells and other biological tissues by pulsed electric fields at elevated temperatures
Publication Date: 2020.07.01 OLD DOMINION UNIVERSITY RESEARCH FOUNDATION
  • EP2793995B1 patent drawingFigure 1A
  • EP2793995B1 patent drawingFigure 1B
  • EP2793995B1 patent drawingFigure 2A~2B

AI summary

Systems and methods for treatment of a biological tissues comprising target tissues and other tissues. The method includes elevating a temperature of the target tissues above a physiological temperature of the biological tissues to treatment temperature, and generating an electric field extending through at least a portion of the target tissues using a pre-defined sequence of short voltage pulses applied between at least two electrodes. In the method, the treatment temperature is maintained during the generating. Further, the pre-defined sequence is selected such that a magnitude of the electric field generated is sufficient to induce electromanipulation in the portion of the target tissues without substantially elevating of the temperature of the portion of the target tissues above the treatment temperature.