Cell Discrimination Using Constant Phase Element Impedance Modeling

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Solution Overview

Problem

Existing methods for determining the type and condition of cells, such as those in tissue structures, face limitations in accuracy and reliability, especially when attempting in vivo measurements, due to variations in membrane capacitance and frequency peaks, making it difficult to differentiate between cell types and conditions like cancerous or healthy states.

Innovation Solution

A method utilizing an equivalent circuit model with a constant phase element to calculate effective capacitance, which compares measured impedance spectra to reference values, allowing for accurate differentiation of cell types and conditions without the need for calibration or normalization, and can be implemented in vivo.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If membrane capacitance measurement is used to differentiate cell types, then cell discrimination is attempted, but the membrane capacitance exhibits strong variations from one cell to another even between two cells of the same type, resulting in limited reliability

Engineering Contradiction:
Improvecell type differentiation accuracyVSAvoidmeasurement reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent changes the measurement parameter from simple membrane capacitance to effective capacitance derived from equivalent circuit model parameters (R1, R2, Q0, α). This transformation converts the unreliable direct capacitance measurement into a more stable derived parameter that accounts for variations in cell properties through the constant phase element model.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an equivalent circuit model as an intermediary between the raw impedance measurement and cell type classification. The model parameters (R1, R2, Q0, α) serve as intermediate variables that capture cell characteristics more reliably than direct capacitance, acting as a mediator that transforms noisy measurements into meaningful diagnostic information.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If frequency peak analysis is used to determine cell type, then cell discrimination is attempted, but the frequency of the peak may vary greatly from one measurement to another and from one test system to another, resulting in limited reliability

Engineering Contradiction:
Improvecell type differentiation accuracyVSAvoidmeasurement repeatability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent transforms the measurement from direct frequency peak analysis to effective capacitance calculation based on equivalent circuit model fitting. This parameter transformation eliminates the variability of peak frequency positions while preserving the discriminatory power for cell type identification through the model-derived parameters Q0 and α.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary impedance spectrum measurement and equivalent circuit model fitting before making cell type determination. By pre-processing the data through model fitting, the method establishes a stable reference framework that reduces measurement-to-measurement variability and enables more reliable cell classification.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If normalized impedance measurement is used with off-load calibration, then cell characterization is attempted, but the method requires off-load measurements with test conditions similar to when the sample is present, which proves difficult to achieve as blood properties may exhibit rapid and significant variations

Engineering Contradiction:
Improvecell characterization accuracyVSAvoidin vivo implementation difficulty
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts the essential cell characteristics from the impedance spectrum by fitting an equivalent circuit model, separating the cell-specific parameters (R1, R2, Q0, α) from the measurement conditions. This extraction allows the method to function without requiring matched off-load calibration conditions, as the model parameters directly represent cell properties independent of blood variations.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The equivalent circuit model serves as a self-calibrating framework that automatically adapts to different measurement conditions. The model parameters are directly determined from each measurement without requiring external calibration references, enabling the system to self-adjust to varying blood properties and eliminate the need for complex off-load calibration procedures.

Inventive Principle:
Principle #25Self-service

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 accurate, fast, and reliable differentiation of cell types and conditions, including cancerous phases, without requiring calibration measurements, and can be applied in vivo, improving upon the limitations of existing techniques.

Implementation Method 1

measuring an impedance spectrum of cellular structures

Methodology Applied
Scientific EffectElectrical Impedance: Electrical Resistance

Implementation Method 2

defining at least one model of the impedance of the cellular structure including a constant phase element... determining the impedance of the constant phase element... deducing... an effective capacitance representative of a set of individual capacitances

Methodology Applied
Scientific EffectCapacitance: Capacitance

Data Source

PatentUS10912482B2Method for determining at least one type and/or condition of cells and system
Publication Date: 2021.02.09 SENSOME
  • US10912482B2 patent drawing
  • US10912482B2 patent drawing
  • US10912482B2 patent drawing

AI summary

The invention relates to a method for discriminating cells of a cellular structure, notably of a cellular tissue, comprising the steps consisting in determining (12) a frequency spectrum of the impedance of the cellular structure; defining (22) at least one model of the impedance of the cellular structure including a constant phase element (30); determining (44) the impedance of the constant phase element (30) which optimizes the correlation of each model of the impedance of the cellular structure with the spectrum; and deducing (66), from the impedance of the constant phase element (30) or from the impedances of the constant phase elements (30), an item of information on the cells of the cellular structure. The invention also relates to a system for implementing the method for discriminating cells of a cellular structure.