Interferometric Scattering Microscopy Particle Characterization

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Solution Overview

Problem

Interferometric scattering optical microscopy (iSCAT) faces challenges in characterizing particles due to small interference signals and difficulty in tracking particles, especially when they move in the depth-direction, leading to interference changes from constructive to destructive, making particle detection and characterization difficult.

Innovation Solution

A method using interferometric scattering optical microscopy that captures and processes a succession of images to determine image correlation values, fitting a decorrelation function to characterize particles by analyzing their decorrelation over time, allowing for the determination of properties such as size, shape, and concentration without the need for particle tracking.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If particle tracking techniques are used to characterize particles in iSCAT, then particle properties can be determined, but the small interference signal makes tracking difficult and particles may disappear when moving in depth-direction

Engineering Contradiction:
Improveparticle tracking precisionVSAvoidtracking reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The interference signal is segmented into multiple correlation values computed at different time points. Instead of attempting to track a single particle through continuous imaging, the method divides the temporal signal into discrete segments and computes correlation values for each segment, thereby avoiding the reliability issues of continuous tracking while preserving measurement precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Instead of tracking particles forward in time to determine their properties, the method inverts the approach by computing correlation values from interference signals and then inferring particle properties from the decorrelation behavior. This inversion transforms an unreliable tracking problem into a reliable correlation analysis problem.

Inventive Principle:
Principle #13The other way round (Inversion)

2Stability of the object's composition

If particles are immobilized on a surface to prevent phase variation, then interference signal stability improves, but particle mobility and natural behavior are restricted

Engineering Contradiction:
Improveinterference signal stabilityVSAvoidparticle mobility
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The method introduces image correlation analysis as an intermediary between the moving particle and the interference signal. Rather than immobilizing particles to stabilize the signal, the correlation analysis mediates the relationship by extracting stable correlation values from the time-varying interference signal, allowing particles to remain mobile while maintaining measurement stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The method changes the parameter being measured from direct particle position to temporal correlation of interference signals. By shifting from spatial tracking to temporal correlation analysis, the system maintains signal stability without requiring particle immobilization, thereby preserving particle mobility and natural behavior.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If multiple images are processed to extract decorrelation signals, then characterization accuracy of single particles improves, but processing complexity and time increase

Engineering Contradiction:
Improvecharacterization accuracyVSAvoidimage processing complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The method extracts only the essential correlation values from the multiple images, rather than performing complex analysis on the full image datasets. By taking out and analyzing only the correlation information, the system achieves high characterization accuracy while minimizing processing complexity and time requirements.

Inventive Principle:
Principle #2Taking out (Extraction)

4Speed

If frame rate is increased to capture particle decorrelation, then measurement of fast dynamics improves, but signal-to-noise ratio decreases

Engineering Contradiction:
Improveframe rateVSAvoidsignal-to-noise ratio
Core Design Contradiction:
SpeedVSIllumination intensity

Solution Approach 1:

The method merges multiple low-signal images through correlation analysis to produce a high-quality measurement. By combining the information from multiple frames through correlation computation, the system achieves both high frame rate capability for capturing fast dynamics and improved signal-to-noise ratio through the constructive combination of correlated signals.

Inventive Principle:
Principle #5Merging (Combining)

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 the characterization of single particles and molecules, even when they are indistinguishable from noise, by processing multiple images to extract decorrelation signals, facilitating accurate determination of particle properties like size, shape, and concentration, and overcoming the limitations of traditional iSCAT techniques.

Implementation Method 1

the signal results from interference between light scattered from the particle and a reference, typically light reflected from a nearby interface

Methodology Applied
Scientific EffectInterference: Interference

Implementation Method 2

light is reflected from the interface to provide the reference light

Methodology Applied
Scientific EffectReflection: Reflection

Implementation Method 3

illuminating a region of a fluid with illuminating light using an objective lens to generate scattered light scattered by one or more particles in the fluid

Methodology Applied
Scientific EffectScattering: Scattering

Data Source

PatentEP4179377B1Interferometric scattering optical microscopy
Publication Date: 2025.10.22 CAMBRIDGE ENTERPRISE LTD
  • EP4179377B1 patent drawingFigure 1
  • EP4179377B1 patent drawingFigure 2a
  • EP4179377B1 patent drawingFigure 2b~2d

AI summary

A method of characterizing one or more particles in a fluid, e.g. a liquid, using interferometric scattering optical (iSCAT) microscopy. The method involves illuminating a region of a fluid using an objective lens so that light is scattered by one or more particles in the fluid. The scattered light and reference light are captured using the objective lens and interfere at an imaging device. A succession of images of the interference is processed to determine image correlation values which define a gradual decorrelation over time from which a property of the particle(s) is determined.