Bipolar Pulsed Electric Fields for Selective Cell Ablation
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Solution Overview
Problem
Existing electroporation techniques for tissue ablation are limited by painful muscle contractions, unpredictable treatment outcomes, and the risk of thermal damage, particularly in low conductivity tissues, due to the use of unipolar pulses and the inability to precisely target aberrant cells without affecting surrounding healthy tissues.
Innovation Solution
The use of high-frequency, bipolar electric pulses with durations on the order of microseconds to nanoseconds, delivered through electrodes placed within or near the target tissue, allows for precise cell death induction while minimizing thermal damage and muscle contractions by enabling current flow through both extracellular and intracellular spaces, thereby reducing voltage drop across low conductivity tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If unipolar pulses are used for electroporation-based tissue ablation, then cell membrane permeabilization is achieved, but painful muscle contractions occur and treatment outcomes become unpredictable
Solution Approach 1:
The patent inverts the conventional unipolar pulse approach by using bipolar pulses with alternating polarity. This inversion prevents net charge accumulation that causes muscle contractions, while maintaining effective transmembrane potential induction for cell ablation. The alternating positive and negative phases cancel out harmful side effects while preserving therapeutic efficacy.
Solution Approach 2:
The patent changes key pulse parameters from conventional settings: using bipolar waveform instead of unipolar, adjusting pulse duration to microsecond-nanosecond scale, and optimizing frequency to high-frequency range. These parameter changes simultaneously reduce muscle contractions and improve treatment predictability by enabling precise control of electroporation effects.
2Reliability
If conventional electroporation pulses are used, then tissue ablation is achieved, but thermal damage occurs particularly in low conductivity tissues
Solution Approach 1:
The patent replaces thermal-based ablation mechanisms with electrical field-based electroporation. By using microsecond-nanosecond bipolar pulses, the system induces cell membrane permeabilization through electrical stress rather than thermal heating, eliminating Joule heating effects that cause thermal damage in low conductivity tissues.
Solution Approach 2:
The patent uses periodic bipolar pulse trains with specific duty cycles and frequencies. The short pulse duration followed by longer intervals between pulses allows complete dissipation of thermal energy, preventing heat accumulation. This periodic action pattern ensures non-thermal ablation by maintaining temperature below damage thresholds while delivering sufficient electrical stress for cell death.
3Manufacturing precision
If electrodes are placed in target tissue for electroporation, then cell death is induced, but surrounding healthy tissues are affected
Solution Approach 1:
The patent applies local quality by using bipolar pulses that create highly localized electric field patterns. The alternating polarity generates field confinement effects where the electric field intensity drops off rapidly with distance from the electrode-tissue interface. This allows precise targeting of abnormal cells while sparing surrounding healthy tissues from excessive field exposure.
Solution Approach 2:
The patent employs dynamic pulse delivery with adjustable parameters including amplitude, duration, frequency, and duty cycle. This dynamic control enables real-time optimization of treatment parameters based on tissue characteristics, maximizing cell death in target areas while minimizing exposure of healthy tissues. The ability to modulate pulse characteristics provides precise spatial and temporal control over electroporation effects.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables precise and non-thermal ablation of target tissues, preserving extracellular matrix and sensitive structures, with predictable treatment outcomes and reduced need for anesthesia, allowing for effective treatment of heterogeneous tissues without significant thermal damage.
Implementation Method 1
The extent of electroporation is attributed to the induced buildup of charge across the plasma membrane, or transmembrane potential (TMP)
Implementation Method 2
delivering high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale
Implementation Method 3
enabling current flow through both extracellular and intracellular spaces, thereby reducing voltage drop across low conductivity tissues
Implementation Method 4
The use of high-frequency, bipolar electric pulses with durations on the order of microseconds to nanoseconds... minimizing thermal damage
Data Source
AI summary
The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.