Electroporation Pulse Control via Impedance Feedback
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Solution Overview
Problem
Current methods for in vivo gene delivery via electroporation face challenges in variability between patients due to differences in tissue properties and conductance, leading to inconsistent and inefficient delivery of molecules.
Innovation Solution
The method involves applying localized temperature increases and real-time impedance-based feedback to adjust electroporation pulse parameters, allowing for more precise control and reduced variability in molecule delivery, using a system that includes an electroporation device with heating elements and impedance measurement systems to monitor and adjust pulse parameters during treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional electroporation methods are used with fixed empirical parameters, then the delivery process is simple to operate, but the delivery consistency and expression levels vary significantly between patients due to tissue property differences
Solution Approach 1:
The patent implements real-time impedance monitoring during electroporation pulses to detect tissue property variations between patients. The system measures impedance changes and uses this feedback to dynamically adjust pulse parameters (voltage, pulse width, number of pulses) to maintain optimal delivery conditions across different patients, thereby improving delivery consistency without requiring complex pre-calibration for each patient
Solution Approach 2:
The system transitions from static empirical parameters to dynamic parameter adjustment based on real-time tissue conditions. Impedance measurements taken during the procedure allow the system to adapt pulse parameters on-the-fly, making the delivery process responsive to actual tissue properties rather than relying on predetermined fixed parameters, thus improving reliability while keeping the interface relatively simple
2Productivity
If higher voltage pulses are applied to ensure adequate molecule delivery, then delivery effectiveness increases, but tissue damage and harmful effects increase
Solution Approach 1:
Real-time impedance monitoring provides feedback on tissue state during electroporation. The system detects impedance changes that indicate adequate membrane permeabilization and molecule uptake, allowing it to terminate pulse application at the optimal point rather than using fixed high-voltage protocols. This prevents excessive voltage application that would cause tissue damage while ensuring sufficient delivery effectiveness
Solution Approach 2:
The patent replaces the mechanical approach of applying fixed high voltage with a sensor-based control system that uses electrical impedance measurements to guide pulse parameter selection. This substitution allows for precise control of energy delivery, matching the electrical parameters to actual tissue conditions rather than using blanket high-voltage protocols, thereby improving delivery effectiveness while reducing tissue damage
3Measurement precision
If multiple experiments are conducted to derive optimal electroporation parameters for each patient, then delivery precision improves, but the time and complexity of the process increase significantly
Solution Approach 1:
The system performs preliminary impedance measurements at the beginning of the procedure to assess tissue properties before applying treatment pulses. This preliminary characterization allows the system to pre-calculate appropriate pulse parameters based on the measured tissue impedance, avoiding the need for multiple experimental trials during the actual treatment procedure and significantly reducing the time required while maintaining parameter optimization accuracy
Solution Approach 2:
Real-time impedance feedback during pulse application provides continuous information about tissue response and membrane permeabilization status. This feedback allows the system to verify that the pre-calculated parameters are achieving the desired effect and to make minor adjustments if needed, ensuring measurement precision without requiring extensive multiple experiments, thus reducing time loss while maintaining accuracy
Data Source
AI summary
A method and system for delivering a molecule to a specific area of a tissue by controlling temperature and impedance is presented. The method is generally comprised of applying heat to a biological structure, such as cells or tissues, to heat the biological structure to a preset temperature after which at least one electroporation pulse is administered to the biological structure. Impedance is measured as a feedback control mechanism after each pulse and pulse parameters are adjusted accordingly until desired impedance is reached. The system generally comprises an electroporation system capable of generating at least one pulse, measuring impedance and measuring temperature. The method may be used to deliver a molecule such as a vaccine or therapeutic to a biological structure, such as for prevention or treatment of SARS-CoV-2 infection.