Subnanosecond HV Pulse Generator With Impedance-Matched Cell Interface
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Solution Overview
Problem
Current methods for studying the interaction of electromagnetic fields with biological cells are limited by the use of long pulse lengths, which reduce the coupling of high electric fields into cells and hinder understanding of membrane dynamics during electroporation.
Innovation Solution
A subnanosecond pulse generator is developed to apply electric field pulses of less than 100 nanoseconds to cells, allowing for precise regulation of cellular physiology and biophysical properties, including gene transcription and sensitization of cells for therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If long pulse lengths are used in electroporation studies, then the coupling of high electric fields into cells is reduced, but the experimental setup and measurement methods remain simpler
Solution Approach 1:
The patent changes the temporal parameter of the electric pulse from microsecond to nanosecond scale (reducing pulse duration by factor of 1000), which fundamentally alters the interaction mechanism with cell membranes and enables observation of ultrafast membrane dynamics that were previously inaccessible
Solution Approach 2:
The patent replaces conventional electrical measurement systems with ultrafast optical measurement techniques (streak camera, photodetectors) to capture membrane potential changes on nanosecond timescales, substituting electrical measurement methods with optical detection methods
2Power
If subnanosecond pulse durations are implemented, then coupling of high electric fields into cells is improved, but the device complexity and measurement requirements increase significantly
Solution Approach 1:
The patent employs periodic pulsed electric fields with nanosecond duration repeated at controlled frequencies, allowing cumulative biological effects while maintaining peak power efficiency and enabling synchronization with detection systems
Solution Approach 2:
The patent introduces optical intermediaries (streak camera, photodetectors, optical amplifiers) to bridge the gap between nanosecond electrical pulses and measurable signals, using optical fields as mediators to detect and characterize the electrical phenomena
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 effective electroperturbation of cells, facilitating the entry of therapeutic agents and allowing for selective targeting and disruption of cellular membranes, thereby enhancing our understanding of cellular responses and potential therapeutic applications.
Implementation Method 1
Electroporation refers to the phenomena of rearranging the structure of the membrane or membranes of cells to introduce or modify porosity across the membrane film, thereby creating a mechanism for transport between the extra-cellular and intracellular fluids, caused by application of an electric field.
Implementation Method 2
The present invention provides a method and apparatus for applying relatively ultrashort, relatively high field strength electric field pulses to a biological cell or tissue. The present system utilizes an avalanche transistor pulse generator to deliver subnanosecond rise time, high voltage pulses to a biological load.
Implementation Method 3
Pulse generators for application of electric field pulses to cells to regulate the physiology and biophysical properties of various cell types, including terminally differentiated and rapidly dividing cells, and tissues.
Data Source
AI summary
Disclosed are methods and systems for subnanosecond rise time high voltage (HV) electric pulse delivery to biological loads. The system includes an imaging device and monitoring apparatus used for bio-photonic studies of pulse induced intracellular effects. The system further features a custom fabricated microscope slide having micro-machined electrodes. A printed circuit board to interface the pulse generator to the micro-machined glass slide having the cell solution is disclosed. An low-parasitic electronic setup to interface with avalanche transistor-switched pulse generation system is also disclosed. The pc-board and the slide are configured to match the output impedance of the pulse generator which minimizes reflection back into the pulse generator, and minimizes distortion of the pulse shape and pulse parameters. The pc-board further includes a high bandwidth voltage divider for real-time monitoring of pulses delivered to the cell solutions.