Cell Membrane Impedance Measurement for CTC Identification

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Solution Overview

Problem

Current methods for identifying circulating tumor cells (CTCs) in blood are inefficient and inaccurate due to similarities in cell morphology and heterogeneous cell size, which complicates the detection of CTCs amidst billions of blood cells.

Innovation Solution

A method involving dielectrophoresis to measure cell membrane impedance by applying an electrical field with varying frequencies, monitoring the crossover frequency, and using electrochemical impedance spectroscopy to differentiate cells based on their response to stimulants, allowing for precise identification and sorting of CTCs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If cell identification is based on morphology and size, then the method is simple to implement, but the accuracy is low due to similar morphology between CTCs and blood cells and heterogeneous cell size

Engineering Contradiction:
Improvecell identification accuracyVSAvoidmeasurement method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the measurement parameter from morphological parameters (size, shape) to electrical parameters (membrane impedance, capacitance). By measuring the electrical properties of cell membranes, the system can distinguish CTCs from blood cells based on their different membrane characteristics, achieving high accuracy without complex morphological analysis. The membrane capacitance measurement specifically targets the electrical property difference between tumor cells and normal cells.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces mechanical/optical measurement methods (microscopy, flow cytometry based on light scattering) with electrical measurement methods. By using electrical impedance spectroscopy to measure membrane capacitance, the system achieves accurate cell identification without the complexity of optical systems or mechanical sorting devices.

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

2Measurement precision

If absolute cell membrane impedance is measured, then the measurement is straightforward, but the identification is incorrect due to cell size heterogeneity

Engineering Contradiction:
Improvecell identification accuracyVSAvoidmeasurement reliability
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent changes from measuring absolute impedance to measuring membrane capacitance specifically. Capacitance is an intrinsic property of the cell membrane that is independent of cell size, allowing accurate identification of CTCs regardless of their size heterogeneity. This parameter change eliminates the confounding effect of variable cell dimensions.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent focuses measurement on the cell membrane specifically rather than the entire cell. By targeting the membrane capacitance property, the measurement captures the local electrical characteristic that differs between CTCs and blood cells, while being insensitive to overall cell size variations.

Inventive Principle:
Principle #3Local quality

3Adaptability or versatility

If multiple cell types are to be identified simultaneously, then the diagnostic value increases, but the measurement and analysis complexity increases

Engineering Contradiction:
Improvemulti-cell type identification capabilityVSAvoidmeasurement system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent uses electrical parameters (membrane capacitance and conductance) that provide naturally separating characteristics for different cell types. Tumor cells, immune cells, and platelets all have distinct membrane electrical properties, allowing simultaneous identification through a single electrical measurement approach without requiring multiple measurement systems.

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 enables accurate and efficient identification and sorting of cells by measuring cell membrane impedance changes over time, correlating with predetermined values to distinguish between different cell types, thereby improving the detection of CTCs and reducing errors.

Implementation Method 1

The dielectrophoretic force on the cell is measured, and a cross-over frequency of the cell is determined. The crossover frequency of the cell is the frequency at which the cell experiences zero DEP force.

Methodology Applied
Scientific EffectDielectrophoresis: Dielectric Permittivity

Implementation Method 2

applying at least one electrical field, characterized by at least one non-zero frequency, which creates a dielectrophoretic (DEP) force on the cell

Methodology Applied
Scientific EffectPolarization: Polarisation

Data Source

PatentEP2781906B1Method for identifying cells
Publication Date: 2021.08.18 INTERUNIVERSITAIR MICRO ELECTRONICS CENT (IMEC VZW)
  • EP2781906B1 patent drawingFigure 1~2
  • EP2781906B1 patent drawingFigure 3
  • EP2781906B1 patent drawingFigure 4~5

AI summary

The present invention provides a method (100) to analyze or identify a cell. The method comprises: providing (101) a cell, stimulating (102) the cell with a stimulant thereby modifying a cell membrane impedance of the cell, monitoring (103) the cell membrane impedance of the cell and identifying (104) the cell based on the monitored cell membrane impedance. A corresponding device is also provided.