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
Engineering 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
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.
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.
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
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.
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.
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
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.
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.
4Reliability
If hyperthermia and electroporation are applied simultaneously to target tissues, then treatment effectiveness is improved, but damage to adjacent healthy tissues increases
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.
Data Source
Figure 1A
Figure 1B
Figure 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.