Impedance-Imaging Cytometry for High-Throughput Rare Cell Detection

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Solution Overview

Problem

Current image cytometry and single cell analysis technologies face challenges in detecting biological samples with rare and subtle properties due to limitations in throughput and information content.

Innovation Solution

A method that combines impedance readouts and imaging information to characterize biological samples, using impedance markers that bind specifically to target analytes, allowing for high-throughput analysis and detailed characterization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional cytometry is used, then throughput is very high (up to 200,000 events per second), but information content is low

Engineering Contradiction:
ImprovethroughputVSAvoidinformation content
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent merges impedance cytometry (providing high throughput) with imaging flow cytometry (providing high information content) into a unified system. The impedance readout measures electrical properties of cells at high speed, while simultaneously captured imaging data provides detailed morphological and spatial information, resolving the contradiction between throughput and information content

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system performs multiple functions simultaneously: impedance measurement for high-throughput classification and imaging for detailed characterization. This multi-functional approach allows the same system to deliver both high throughput and high information content without requiring separate specialized instruments

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Loss of information

If fluorescence microscopy is used, then information content is very high (spatial resolution, spectral resolution, temporal resolution), but throughput is low

Engineering Contradiction:
Improveinformation contentVSAvoidthroughput
Core Design Contradiction:
Loss of informationVSProductivity

Solution Approach 1:

The system segments the analysis process into two complementary parts: rapid impedance measurement for initial cell classification and targeted imaging for detailed analysis. This segmentation allows the system to maintain high throughput through impedance screening while applying high-information imaging only where needed, thus resolving the throughput-information contradiction

Inventive Principle:
Principle #1Segmentation

3Productivity

If imaging flow-through is used, then medium throughput and medium information content are achieved, but detection of rare and subtle phenotypes remains limited

Engineering Contradiction:
ImprovethroughputVSAvoiddetection sensitivity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent replaces reliance solely on optical imaging with a hybrid approach that incorporates electrical impedance measurement. Impedance provides complementary biophysical information about cell properties that enhances detection sensitivity for rare and subtle phenotypes, while maintaining the medium throughput capability of imaging flow-through

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

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

Enables efficient and accurate characterization of biological samples by increasing both throughput and information content, allowing for the detection of rare and subtle properties.

Implementation Method 1

the impedance marker is configured to change the impedance of the biological sample

Methodology Applied
Scientific EffectImpedance change: Electrical Resistance

Implementation Method 2

The marker comprises an affinity reagent configured to specifically bind to a target analyte of the biological sample

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Data Source

PatentEP4560291A1Method, marker and system for characterising a biological sample
Publication Date: 2025.05.28 LEICA MICROSYSTEMS CMS GMBH
  • EP4560291A1 patent drawingFigure 1
  • EP4560291A1 patent drawingFigure 2
  • EP4560291A1 patent drawingFigure 3

AI summary

A method for characterising at least one biological sample is provided. The method comprises the steps of generating an impedance readout of the biological sample, generating imaging information of the biological sample, and characterising the biological sample based on the impedance readout and on the imaging information. In further aspects, a marker and a system for characterising the biological sample is provided.