Turbidity Light Scattering for Sample Adequacy Control

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Solution Overview

Problem

Current methods for determining sample adequacy in clinical diagnostics, particularly for HPV testing, often result in inaccurate or unrepresentative test results due to inadequate sample acquisition and contamination, leading to unnecessary testing and potential misrepresentation of patient health status.

Innovation Solution

A Sample Adequacy Control Measurement System (SAM) using turbidity light scattering techniques to non-destructively assess sample cellularity, allowing for the determination of sample adequacy before testing, thereby preventing the processing of inadequate samples and ensuring representative test results.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If light scattering techniques are used to measure sample adequacy, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
Improvesample adequacy determination accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical cell counting methods with optical light scattering techniques. The system uses a light source and detector to measure turbidity and determine sample adequacy, eliminating the need for manual microscopy and cell counting while achieving higher precision and automation.

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

Solution Approach 2:

The patent introduces turbidity measurement as an intermediary parameter to assess sample adequacy. Rather than directly counting cells, the system measures light scattering properties of the sample, which correlate with cell density, providing an indirect but accurate method for determining adequacy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of time

If sample adequacy is determined before testing, then loss of time is reduced by avoiding unnecessary testing, but measurement precision requirements increase

Engineering Contradiction:
Improvetesting timeVSAvoidadequacy assessment accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent performs sample adequacy assessment before conducting the main diagnostic testing. By measuring turbidity and determining cell density in advance, the system identifies inadequate samples that should not proceed to costly and time-consuming HPV testing, thereby saving time and resources.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent establishes specific turbidity thresholds and cell density criteria to objectively determine sample adequacy. By defining quantitative parameters for adequacy assessment, the system achieves high measurement precision that enables reliable pre-screening decisions.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If traditional sampling methods are used, then ease of operation is maintained, but reliability of test results deteriorates due to inadequate samples

Engineering Contradiction:
Improvesampling procedure simplicityVSAvoidtest result accuracy
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent implements a feedback mechanism where turbidity measurement results immediately inform whether a sample is adequate for testing. This feedback loop allows operators to identify and reject inadequate samples before they compromise test reliability, while maintaining simple sampling procedures.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent replaces subjective visual assessment of sample adequacy with objective optical measurement. The light scattering technique provides quantifiable data on cell density, eliminating operator variability and ensuring consistent reliability judgments without complicating the sampling process.

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

The system effectively determines sample adequacy, reducing the likelihood of false negative results, saving resources by halting unnecessary testing and providing confidence in test outcomes, while ensuring that only representative samples are analyzed.

Implementation Method 1

A sample is illuminated by a light source and a detector situated to detect light scattered from particles in the sample is provided.

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 2

measuring the turbidity of the sample

Methodology Applied
Scientific EffectTurbidity: Tyndall Effect

Data Source

PatentEP2438438B1Ensuring sample adequacy using turbidity light scattering techniques
Publication Date: 2019.07.10 BECTON DICKINSON & CO
  • EP2438438B1 patent drawingFigure 1
  • EP2438438B1 patent drawingFigure 2
  • EP2438438B1 patent drawingFigure 3

AI summary

Cervical cancer screening using HPV testing can yields a high negative predictive value of approximately 99.5% for prediction of cervical lesions of CIN3 or greater. However, sample adequacy can affect the number of at-risk women that may go undetected due to the inadequacy of the tested sample. We have approached this challenge of increasing sample assurance of the negative results by estimating the cell count in known fluid volumes using light scattering techniques, in particular turbidity. These methods may be used as a fast, convenient, and economical method for measuring sample adequacy for other uses as well. Particular examples using these methods in conjunction with the HC2 HPV test are provided herein.