Selective Cell Disruption via Resonant Harmonic Excitation
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Solution Overview
Problem
Current cancer treatments face challenges in selectively targeting and ablating unhealthy cells within healthy tissue, particularly in cancers with poorly defined borders and vital tissues, where standard methods often damage healthy cells alongside target cells.
Innovation Solution
The use of low-intensity focused ultrasound harmonic excitation tuned to specific frequencies and pulse durations that resonate with target cells, such as neoplastic cells, to induce membrane disruption and lysis while sparing off-target cells, utilizing elastography imaging to determine optimal parameters for selective targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard ablation methods are used to destroy target cells, then cell disruption is achieved, but healthy cells are damaged alongside target cells
Solution Approach 1:
The patent applies resonant mechanical vibration at specific frequencies to induce selective membrane disruption in target cells. By tuning the ultrasound frequency to match the natural resonant frequency of target cell membranes, large amplitude vibrations are generated that cause selective lysis of target cells while sparing healthy cells with different resonant frequencies.
Solution Approach 2:
The patent changes physical parameters (frequency, pulse duration, intensity) of the ultrasound excitation to achieve selective targeting. By adjusting these parameters based on the mechanical properties determined through elastography, the system optimizes the resonant excitation conditions for target cells while minimizing effects on healthy cells.
2Manufacturing precision
If high intensity ultrasound is applied to ensure target cell disruption, then cell lysis is achieved, but off-target cells are also affected
Solution Approach 1:
The patent applies local quality by delivering focused ultrasound energy precisely to the region containing target cells. The focused ultrasound beam concentrates acoustic energy at a specific focal point within the tissue, ensuring that only cells in the focal region are exposed to sufficient intensity for resonant disruption, while surrounding healthy cells receive minimal energy.
Solution Approach 2:
The patent uses resonant mechanical vibration at specifically tuned frequencies to differentiate between target and off-target cells. Each cell type has characteristic resonant frequencies based on its mechanical properties; by selecting frequencies that match target cell resonances, selective vibration and disruption are achieved without affecting off-target cells with different resonant characteristics.
3Productivity
If conventional treatment methods are used on tumors with poorly defined borders, then tumor cells are treated, but healthy tissue is damaged
Solution Approach 1:
The patent employs resonant mechanical vibration to achieve selective tumor cell disruption even when tumor borders are poorly defined. The resonant frequency approach allows differentiation between malignant and healthy cells based on their intrinsic mechanical properties rather than relying on clear anatomical boundaries, enabling treatment of infiltrative tumors while preserving healthy tissue.
Solution Approach 2:
The patent incorporates elastography imaging to provide real-time feedback on the mechanical properties of tissues during treatment. This feedback loop allows dynamic adjustment of ultrasound parameters (frequency, intensity, focus) based on measured tissue characteristics, ensuring continuous optimization of selectivity and effectiveness throughout the treatment process.
4Object-affected harmful factors
If resonant frequency excitation is used to selectively disrupt target cells, then healthy cells are spared, but precise determination of mechanical properties is required
Solution Approach 1:
The patent uses elastography imaging to non-invasively measure and map the mechanical properties (stiffness, elasticity) of tissues in real-time. This feedback information about tissue mechanical characteristics is then used to determine the optimal resonant frequencies and other parameters for selective target cell disruption, eliminating the need for complex ex-vivo measurements.
Solution Approach 2:
The system performs self-characterization by using elastography to automatically determine the mechanical properties of the patient's own tissues at the treatment site. This eliminates the need for external reference measurements or complex calibration procedures, as the system adapts to the specific mechanical properties of the individual patient's tissue being treated.
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 allows for precise ablation of target cells with minimal damage to healthy cells, enhancing the safety and efficacy of cancer therapy by exploiting the unique mechanical properties of cancer cells to induce selective permeabilization or lysis, potentially synergizing with immunotherapy and chemotherapy.
Implementation Method 1
resonance occurs when the external excitation applied has the same frequency as the natural frequency of the system. It leads to large displacements
Implementation Method 2
Harmonic excitation refers to a sinusoidal external force of a certain frequency applied to a system
Implementation Method 3
low intensity focused ultrasound transduction tuned to the selected frequency and pulse duration to induce target cell permeabilization or lysis
Data Source
AI summary
Systems and methods for targeting specific cell types by selective application of ultrasonic harmonic excitation at a resonance frequency (“oncotripsy”) for the specific cell types are presented. The systems and the methods result in permeabilization, lysis, and/or death of the targeted specific cell types by using ultrasonic harmonic excitations that have a frequency and a pulse duration specifically tuned to disrupt nuclear membranes of the targeted specific cell types by inducing a destructive vibrational response therein while leaving non-targeted cell types intact. Target cells may be neoplastic.