Particle Suspensions for Low-Contrast Liquid Inspection

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Solution Overview

Problem

Current calibration and validation methods using polystyrene beads are inadequate for optical instruments analyzing biological particles due to refractive index and shape differences, leading to misclassification and erroneous analysis results, especially for low-contrast and irregularly shaped particles.

Innovation Solution

A standard particle suspension with refractive indices between 1.34 and 1.42, formed from materials like PTFE, ETFE, and PDMS, and designed to mimic biological particles in size, shape, and refractive index, is used to calibrate and validate optical analysis instruments, ensuring accurate detection and counting of biological particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If polystyrene beads are used for calibration, then calibration is simple and beads are readily available, but the refractive index mismatch causes misclassification of biological particles

Engineering Contradiction:
Improvecalibration simplicityVSAvoidparticle detection accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent changes the refractive index parameter of calibration particles by using materials like PTFE (n=1.35), ETFE (n=1.40), or PDMS (n=1.41) instead of polystyrene (n=1.59). This parameter change ensures the calibration particles have refractive indices (1.34-1.42) that match biological particles, thereby resolving the measurement precision issue while maintaining calibration simplicity.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If polystyrene beads are used for calibration, then uniform spherical shape provides consistent calibration, but irregular shapes of biological particles are not represented

Engineering Contradiction:
Improvecalibration consistencyVSAvoidparticle shape coverage
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent applies asymmetry by providing calibration particles with irregular shapes (ellipsoidal, threadlike, amorphous, crystalline) that match biological particles, rather than using uniform spheres. This allows the calibration standard to represent the diverse shapes of actual biological particles while maintaining composition stability through controlled synthesis methods.

Inventive Principle:
Principle #4Asymmetry

3Illumination intensity

If polystyrene beads with higher refractive index are used, then optical signal is stronger for calibration, but low-contrast biological particles generate weaker signals and may be eliminated from analysis

Engineering Contradiction:
Improveoptical signal strengthVSAvoiddetection threshold accuracy
Core Design Contradiction:
Illumination intensityVSReliability

Solution Approach 1:

The patent changes the refractive index parameter of calibration particles to match biological particles (n=1.34-1.42), which reduces the optical signal strength compared to polystyrene beads. However, this parameter change ensures that the detection threshold and analysis parameters are calibrated accurately for low-contrast particles, improving reliability by preventing elimination of valid biological particle events.

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

The standard particle suspension improves the accuracy of instrument calibration and validation, reducing errors in particle detection and allowing for consistent comparison across instruments and laboratories, by closely matching the properties of biological particles and providing a stable, reproducible reference for adjusting instrument parameters.

Implementation Method 1

Instruments used to inspect (detect) micron sized particles typically involve imaging, or light scattering, or light obscuration of the particles as they flow through a clear flow cell

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 2

Instruments used to inspect (detect) micron sized particles typically involve imaging, or light scattering, or light obscuration of the particles as they flow through a clear flow cell

Methodology Applied
Scientific EffectLight obscuration: Absorption (EM radiation)

Data Source

PatentEP3019850B1Particle suspensions used as low-contrast standards for inspection of liquids
Publication Date: 2020.05.20 KLA CORP
  • EP3019850B1 patent drawingFigure 1~3
  • EP3019850B1 patent drawingFigure 4~5

AI summary

In certain embodiments, a method for validating the human visual inspection process or an optical analysis instrument for use with biological particles may include inspecting a standard particle solution using the optical analysis instrument. The standard particle solution may include a known concentration of standard particles suspended in solution with the standard particles having a defined size and shape distribution. The standard particles may have a refractive index that is substantially similar to a refractive index of the biological particles. The method may include assessing a concentration of standard particles in the standard particle solution from the inspection. The method may include assessing a difference between the assessed concentration of standard particles and the known concentration of standard particles. The method may include modifying one or more parameters of the optical analysis instrument based on the assessed difference between the concentrations. The method may include assessing a detection efficiency of the optical analysis instrument.