Particle Imaging Accuracy via Interpolation and Gaussian Deconvolution

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Solution Overview

Problem

Current particle imaging technologies face challenges in accurately measuring the intensity and location of particles, especially when they overlap, leading to errors in fluorescence measurement due to overlapping light contributions from nearby particles.

Innovation Solution

The method involves creating higher-resolution images through interpolation, determining the center of particles, and subtracting the contribution of overlapping light from nearby particles using Gaussian distribution calculations, with the option to discard measurements if the overlap exceeds a predetermined threshold, employing CCD, CMOS, or quantum dot detectors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If linear interpolation is used to increase resolution, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
Improveparticle location measurement accuracyVSAvoidimage processing complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by performing interpolation to create a high-resolution image before conducting edge detection and particle analysis. This preprocessing step establishes a more accurate spatial framework that improves subsequent measurement precision without requiring complex hardware modifications.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces mechanical/optical resolution enhancement with computational methods. Instead of using higher-resolution detectors or more complex optical systems, the invention uses software-based interpolation and image processing algorithms to achieve sub-pixel measurement accuracy, thereby improving precision while avoiding increased device complexity.

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

2Productivity

If light from overlapping particles is measured, then productivity is improved, but measurement precision deteriorates due to light contribution errors

Engineering Contradiction:
Improveparticle measurement throughputVSAvoidfluorescence intensity accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies segmentation by separating the light contributions from overlapping particles through iterative deconvolution. The measured light distribution is divided into individual particle components, allowing each particle's fluorescence intensity to be determined independently even when their images overlap, thus maintaining both productivity and measurement precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses feedback by iteratively refining the separation of overlapping particle signals. The initial particle location estimates are used to model expected light distributions, which are then compared to actual measurements and used to update particle parameters in subsequent iterations, progressively improving measurement precision while processing multiple particles efficiently.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If measurements are discarded due to overlap threshold, then measurement precision is improved, but productivity decreases

Engineering Contradiction:
Improveparticle intensity measurement accuracyVSAvoidvalid particle measurements per unit time
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies parameter changes by dynamically adjusting the overlap threshold based on signal-to-noise ratios and particle intensity characteristics. Rather than using a fixed threshold that discards measurements, the system adapts the criterion for accepting measurements based on actual data quality, thereby maintaining precision while maximizing the number of valid measurements and improving overall productivity.

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 enhances measurement accuracy by isolating the light contribution from individual particles, reducing errors caused by overlap, and allowing for more precise determination of particle intensity and location, thereby improving the overall accuracy of particle imaging.

Implementation Method 1

the CCDs are configured to measure fluorescent light emitted by particles in response to a light source

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

The linear interpolation is based on four pixels which are weighted according to the distance of the interpolated pixel

Methodology Applied
Scientific EffectLinear interpolation:

Implementation Method 3

determining the contribution of light from the second particle in the overlap region may include calculating a Gaussian distribution of light from the second particle

Methodology Applied
Scientific EffectGaussian distribution:

Data Source

PatentEP2588846B1System and method for increasing measurement accuracy in a particle imaging device using light distribution
Publication Date: 2019.10.23 LUMINEX CORP
  • EP2588846B1 patent drawingFigure 1
  • EP2588846B1 patent drawingFigure 2A~2B
  • EP2588846B1 patent drawingFigure 3

AI summary

An apparatus, system, and method for increasing measurement accuracy in imaging cytometry. The system may include a light detector configured to measure light emitted by a particle in response to a first light source, and processor coupled to the light detector. The processor may be configured create a first image by taking a first measurement of light and create a second image by interpolating the first image, where the second image has higher resolution than the first image. The processor may be configured to determine a difference between pixels of the second image and an expected distribution and discard the first measurement of light if the difference is above a predetermined threshold.