Cell Adhesion Characterization via Optical Diffraction

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Solution Overview

Problem

Current methods for studying cell adhesion to a substrate are costly, time-consuming, and difficult to implement, often requiring reagents that can interfere with cell viability and do not allow for continuous or high-throughput measurements of thousands of cells simultaneously.

Innovation Solution

A characterization system comprising a spatially coherent light source and a matrix photodetector that acquires images of particles in a liquid medium, with an information processing unit calculating primary and secondary indicators of cell adhesion and spreading without the need for labeling or reagents, enabling continuous monitoring and statistical analysis of cell adhesion states.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods using reagents and labeling are used to study cell adhesion, then measurement precision can be achieved, but device complexity and cost increase significantly

Engineering Contradiction:
Improvecell adhesion measurementVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical and chemical systems (reagents, labeling, washing steps) with an optical system based on light diffraction. The system uses a light source and detector to measure diffraction patterns generated by cells adhering to the surface, eliminating the need for complex biochemical manipulations while maintaining measurement capability.

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

Solution Approach 2:

The patent creates an optical copy or representation of cell adhesion state through diffraction patterns. Instead of directly measuring biochemical adhesion properties, the system captures light diffraction patterns that encode information about cell position, morphology, and adhesion state, converting biological information into optical signals for analysis.

Inventive Principle:
Principle #26Copying

2Measurement precision

If multiple washes and optical acquisitions are performed to study cell adhesion, then measurement accuracy improves, but loss of time increases

Engineering Contradiction:
Improveadhesion characterization accuracyVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent enables continuous measurement of cell adhesion without interrupting the process for washing or reagent addition. The optical system can continuously monitor diffraction patterns as cells adhere to the surface in real-time, providing continuous data streams that eliminate idle time between measurement steps.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system performs measurements in a label-free manner from the beginning, without requiring preliminary labeling steps or subsequent washing steps to remove reagents. The diffraction-based measurement works directly on native cells, eliminating time-consuming preparatory and cleanup procedures.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If fluorescent labeling combined with flow cytometry is used, then cell adhesion can be quantified, but object-affected harmful factors increase due to sample destruction

Engineering Contradiction:
Improveadhesion quantificationVSAvoidsample destruction
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses the cells' own physical properties (light diffraction caused by cell morphology and position) to generate the measurement signal. The cells serve their own function of creating the diffraction pattern without requiring external labels or reagents, enabling measurement without sample destruction or modification.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces destructive mechanical and chemical processes (flow cytometry, fluorescent labeling) with non-invasive optical diffraction measurement. The light-based system measures cell adhesion by detecting changes in diffraction patterns caused by cell attachment, preserving cell viability and eliminating sample destruction.

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

4Measurement precision

If reagents are added to the liquid medium to study cell adhesion, then measurement capability improves, but object-generated harmful factors increase due to interference with cell life

Engineering Contradiction:
Improveadhesion detectionVSAvoidcell viability interference
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The measurement system exploits the natural optical properties of living cells (their ability to diffract light based on their shape, size, and position) without requiring any external chemicals. The cells' own physical characteristics provide the measurement signal, eliminating the need for reagents that could interfere with cell metabolism or viability.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent extracts and utilizes the inherent optical diffraction property of cells for measurement purposes. By focusing on the natural light-diffraction capability of cells rather than introducing external labeling agents, the system isolates and amplifies the useful optical signal while removing harmful chemical interventions.

Inventive Principle:
Principle #2Taking out (Extraction)

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 system allows for cost-effective, efficient, and non-destructive characterization of cell adhesion and spreading, enabling continuous monitoring of thousands of cells in parallel, reducing the need for reagents and avoiding interference with cell viability.

Implementation Method 1

The matrix photodetector is suitable for measuring the intensity I of at least one elementary diffraction pattern transmitted by the illuminated medium (24), each elementary diffraction pattern corresponding to waves diffracted by a diffracting particle (22)

Methodology Applied
Scientific EffectDiffraction: Diffraction

Data Source

PatentEP3114459B1Method and system for characterising a state of adhesion of particles such as cells
Publication Date: 2021.09.29 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP3114459B1 patent drawingFigure 1~2
  • EP3114459B1 patent drawingFigure 3~4
  • EP3114459B1 patent drawingFigure 5~6

AI summary

This method for characterising a state of adhesion of particles is implemented via a system comprising a spatially coherent light source and a matrix-array photodetector, the particles being contained in a liquid medium, the liquid medium being bounded by a transparent surface, the particles being able to adhere to said transparent surface. This method comprises the following steps: illuminating (100) the medium with the spatially coherent light source; acquiring (110) at least one image using the matrix-array photodetector, the image being formed by radiation transmitted by the illuminated medium, and comprising at least one elementary diffraction pattern, each elementary diffraction pattern corresponding to waves diffracted by a particle during the illumination of the medium; and, calculating (120), from at least one acquired image and for at least one particle, a primary indicator characterising the state of adhesion of the particle to the transparent surface.