Electrochemical Impedance Spectroscopy System for Bioparticle Characterization

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Solution Overview

Problem

Electrochemical impedance spectroscopy (EIS) measurements on cell cultures face challenges due to variability in electrode connections, timing of active compound addition, and external environmental fluctuations, which affect measurement reliability and interpretation.

Innovation Solution

A system for continuously measuring electrochemical data, comparing it with reference data to determine the optimal time for adding an active compound, and using a substrate holder with short electrical connections to reduce variability, while monitoring environmental parameters to account for their impact.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If measurements are performed in the lower frequency range (1-100 kHz) to obtain qualitative data, then measurement quality is improved, but measurement time increases and time resolution is reduced

Engineering Contradiction:
Improvemeasurement qualityVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The system performs preliminary actions by continuously monitoring electrochemical parameters and comparing them with reference data before the optimal addition moment is reached. This allows the system to prepare and execute compound addition at the precise optimal time, ensuring high measurement quality without excessive measurement time. The continuous monitoring and prediction approach enables timely intervention based on anticipated cell behavior.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system implements feedback by continuously measuring electrochemical parameters, comparing them with reference data, and using this information to determine the optimal moment for compound addition. The feedback loop enables real-time adjustment of measurement and addition timing, maintaining high measurement quality while optimizing measurement duration through intelligent control.

Inventive Principle:
Principle #23Feedback

2Duration of action of moving object

If the active compound is added early to the cell culture, then more interaction time is available, but growth kinetics interfere with measurements

Engineering Contradiction:
Improveinteraction timeVSAvoidmeasurement reliability
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The system performs preliminary monitoring of electrochemical parameters and compares them with reference data to predict when cells will reach the optimal state for compound interaction. This preliminary action enables the system to add the compound at the precise optimal moment, ensuring sufficient interaction time while avoiding the period when growth kinetics interfere with measurements.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system replaces mechanical timing methods with electrochemical sensing and automated control. By using electrochemical impedance spectroscopy to monitor cell behavior and automated systems to determine and execute compound addition, the system achieves precise timing that ensures reliable measurements while maximizing interaction time.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If the active compound is added late to the cell culture, then growth interference is minimized, but cells are already dying due to competition

Engineering Contradiction:
Improvemeasurement reliabilityVSAvoidinteraction time
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The system performs preliminary continuous monitoring of electrochemical parameters and compares them with reference data to predict the optimal addition moment before cells enter the death phase. This allows the system to add the compound at the precise optimal time, ensuring cells are still viable and providing sufficient interaction time while avoiding growth interference.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system uses feedback from continuous electrochemical monitoring to determine the optimal addition moment. By continuously comparing measured parameters with reference data, the system receives real-time feedback on cell state, enabling it to add the compound at the precise moment when cells are healthy and ready for interaction, thus maintaining both reliability and interaction duration.

Inventive Principle:
Principle #23Feedback

4Productivity

If multiple wells are used for measurements with varying lead geometries, then throughput is increased, but variability in readout increases

Engineering Contradiction:
Improvemeasurement throughputVSAvoidreadout consistency
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system changes the electrical connection parameter by implementing short and identical electrical connections for all wells. This parameter change eliminates the variability caused by different lead geometries, ensuring consistent readout across multiple wells while maintaining high throughput through parallel measurement capability.

Inventive Principle:
Principle #35Parameter changes

5Measurement precision

If reference wells are used to counter variability, then measurement consistency is improved, but additional wells are required and data analysis complexity increases

Engineering Contradiction:
Improvemeasurement consistencyVSAvoiddata analysis complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system changes the electrical connection parameter to short and identical connections for all wells, which eliminates the need for reference wells. This parameter change simplifies the measurement setup and data analysis while maintaining measurement consistency across all wells through standardized electrical connections.

Inventive Principle:
Principle #35Parameter changes

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 improves the quality and reproducibility of EIS measurements by ensuring precise compound addition and minimizing external influences, leading to more accurate characterization of bioparticles and reduced measurement duration and costs.

Implementation Method 1

Electrochemical impedance spectroscopy (EIS) methods are used to investigate cell cultures in a non-invasive manner

Methodology Applied
Scientific EffectElectrochemical impedance spectroscopy:

Data Source

PatentUS11513089B2Systems and methods for conducting electrochemical impedance spectroscopy
Publication Date: 2022.11.29 VRIJE UNIV BRUSSEL
  • US11513089B2 patent drawing
  • US11513089B2 patent drawing
  • US11513089B2 patent drawing

AI summary

A system for measuring electrical characteristics of bioparticles is described. The system comprises an incubator for performing electrochemical measurements in a defined environment and a substrate holder positioned in said incubator for holding a substrate comprising a plurality of wells. The system is furthermore configured for continuously or regularly measuring electrochemical data. The system also comprises a processing means for comparing the continuously or regularly measured electrochemical data with reference data and for determining a moment for adding an active compound based on said comparison.