Electroporation Pulse Control After Lightning Discharge

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing methods for introducing bioactive molecules into cells using electrical fields often result in unpredictable and irreproducible results due to premature termination of voltage pulses, leading to reduced transfection efficiency and cell viability issues, particularly from lightning discharges.

Innovation Solution

Continuing the first voltage pulse with additional voltage pulses after termination, ensuring cells are exposed to the electrical field for the originally set duration, thereby maintaining treatment success and reproducibility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a voltage pulse is terminated early to prevent lightning discharge, then cell damage is avoided, but transfection efficiency decreases

Engineering Contradiction:
Improvecell viabilityVSAvoidtransfection efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The voltage pulse is segmented into multiple separate pulses instead of one continuous pulse. When a lightning discharge is detected, the current pulse is terminated and replaced by one or more additional voltage pulses, effectively dividing the treatment into discrete segments that can be controlled independently to avoid cell damage while maintaining transfection efficiency

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system performs preliminary monitoring of electrical parameters during voltage pulse application and prepares additional voltage pulses in advance. When lightning discharge is detected, the pre-prepared additional pulses are immediately applied to compensate for the incomplete treatment, ensuring that the total exposure duration and transfection effect are maintained

Inventive Principle:
Principle #10Preliminary action

2Productivity

If the voltage pulse duration is extended to improve transfection efficiency, then more cells are successfully treated, but the risk of lightning discharge increases

Engineering Contradiction:
Improvetransfection efficiencyVSAvoidlightning discharge risk
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The system continuously monitors electrical parameters (current, voltage, resistance) during voltage pulse application and uses this feedback to detect lightning discharge conditions in real-time. Based on the feedback signal indicating abnormal current rise or resistance collapse, the control system automatically terminates the current pulse and applies additional compensating pulses, creating a closed-loop control system that adapts to changing conditions

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The voltage pulse protocol is made dynamic rather than static. The system adjusts the number, duration, and timing of voltage pulses based on real-time detection of lightning discharge events. The pulse sequence can be modified on-the-fly, applying additional pulses after termination to compensate for incomplete treatment, making the overall process adaptive to actual cellular responses

Inventive Principle:
Principle #15Dynamics

3Reliability

If overcurrent protection terminates the voltage pulse, then safety is improved, but treatment completeness is compromised

Engineering Contradiction:
ImprovesafetyVSAvoidtreatment consistency
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

When lightning discharge causes premature termination of a voltage pulse, the system discards the incomplete pulse and recovers by applying one or more additional voltage pulses to compensate for the lost treatment time. This ensures that even though individual pulses may be interrupted, the overall treatment completeness is recovered and maintained through the application of supplementary pulses

Inventive Principle:
Principle #34Discarding and recovering

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

Significantly increases transfection efficiency in electroporation of eukaryotic cells by ensuring consistent exposure to the electrical field, reducing the risk of cell damage and improving result reproducibility.

Implementation Method 1

In electroporation, the foreign molecules are taken from a buffer solution adapted to the cells or a cell culture medium and introduced into the cells in a brief flow of current, wherein exposure to the short electrical voltage pulses or resultant electrical field makes the cell membrane permeable to the foreign molecules.

Methodology Applied
Scientific EffectElectroporation: Electrical Impedance Tomography

Implementation Method 2

Briefly applying a strong electrical field, i.e., a short voltage pulse with a high current density, also makes it possible to fuse cells, cell derivates, sub-cellular particles and/or vesicles. During this so-called electrofusion, the cells are, for example, initially brought into close membrane contact by an inhomogeneous electrical alternating field. The subsequent application of an electrical field pulse then causes the membrane sections to interact, finally resulting in fusion.

Methodology Applied
Scientific EffectElectrofusion: Electrical Impedance Tomography

Implementation Method 3

Further, living cells can also be stimulated by electrical fields in such a way as to change their properties.

Methodology Applied
Scientific EffectElectrostimulation: Electrical Impedance Tomography

Implementation Method 4

If, in the process of establishing an electrical field with a field strength of several hundred volts per centimeter in an aqueous solution, the electrical resistance collapses in a very short time, e.g., under 1 μs, thereby causing the current to rise very rapidly and sharply, a so-called lightning discharge can occur.

Methodology Applied
Scientific EffectLightning discharge: Electrical Discharge Machining

Data Source

PatentUS7732175B2Method and circuit arrangement for treating biomaterial
Publication Date: 2010.06.08 LONZA COLOGNE AG
  • US7732175B2 patent drawing
  • US7732175B2 patent drawing
  • US7732175B2 patent drawing

AI summary

The invention relates to a method for treating biomaterial using at least one electrical field generated by a first voltage pulse which is terminated once the value for an electrical parameter has exceeded or dropped below a preset limit. After the first voltage pulse has been terminated, it is continued by an additional voltage pulse. The invention also relates to a circuit arrangement comprising at least one storage device for electrical charges to generate at least one voltage pulse by selectively discharging the storage device, and at least one control unit for controlling the discharge. The present invention provides a controller for monitoring the chronological progression of the voltage pulse. This controller controls at least one continuation of discharge after termination.