In-line Flow Cell for Hemoglobin Quantification

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Solution Overview

Problem

Current methods for analyzing hemoglobin components in biological samples, such as blood tests, face challenges due to variability in total and group amounts of hemoglobin, leading to inaccuracies in chromatographic peak areas and quantification, particularly in HPLC applications, where dilution ratio control is difficult and results in inconsistent sample concentrations.

Innovation Solution

A method involving the creation of fluid paths between low and high-pressure pumps and a detector, with real-time absorbance integration to determine a time interval for forming a sample plug, ensuring a predetermined quantity of hemoglobin is diverted to a detector, allowing for precise quantification and consistent testing results by controlling the denominator response value.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If strict control of total hemoglobin amount is maintained by diluting sample to fixed concentration and testing fixed volume, then quantification accuracy is improved, but device complexity and operation difficulty increase

Engineering Contradiction:
Improvequantification accuracyVSAvoiddilution control complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical dilution control system with an optical detection system. Instead of relying on precise mechanical dilution to achieve fixed hemoglobin concentration, the system uses an optical detector to measure the total hemoglobin amount in real-time and provides feedback for dynamic adjustment, substituting mechanical precision requirements with optical measurement and control.

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

Solution Approach 2:

The patent implements a feedback mechanism where the optical detector continuously monitors the total hemoglobin amount in the flowing sample and provides real-time information to the control system. This feedback allows dynamic adjustment of the sampling rate or dilution ratio to maintain the total hemoglobin amount within the optimal range, eliminating the need for strict pre-dilution control.

Inventive Principle:
Principle #23Feedback

2Ease of operation

If dilution ratio is controlled within tolerance range, then ease of operation is improved, but measurement precision deteriorates due to concentration variability

Engineering Contradiction:
Improvedilution control easeVSAvoidhemoglobin concentration accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent transitions from a static dilution approach (fixed dilution ratio) to a dynamic control system. The system continuously adjusts the sampling rate or dilution ratio based on real-time optical detection of total hemoglobin amount, allowing the operating parameters to vary dynamically while maintaining measurement accuracy. This dynamic adaptation eliminates the trade-off between ease of operation and measurement precision.

Inventive Principle:
Principle #15Dynamics

3Productivity

If fixed volume of diluted sample is tested, then productivity is improved, but measurement precision worsens due to total amount variability

Engineering Contradiction:
Improvetesting throughputVSAvoidchromatographic peak area accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent uses real-time optical detection of total hemoglobin amount as feedback to control the sampling process. The system monitors the cumulative hemoglobin amount and dynamically adjusts the sampling rate to ensure a fixed total amount is achieved, providing feedback control that maintains precision while enabling continuous high-throughput operation.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system performs self-regulation by using its own optical detection capability to monitor and control the total hemoglobin amount. The detector provides real-time information that automatically adjusts the sampling process, allowing the system to self-correct for variations in sample concentration without external intervention, thereby maintaining precision at high throughput.

Inventive Principle:
Principle #25Self-service

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 provides improved consistency and accuracy in hemoglobin quantification by ensuring a fixed amount of hemoglobin is processed, reducing the need for exact concentration control and minimizing the impact of concentration variations between samples, thereby enhancing test reliability and predictive capabilities for diseases like diabetes.

Implementation Method 1

flowing the sample at a low pressure through an absorbance detector along the first fluid path

Methodology Applied
Scientific EffectAbsorbance: Absorption Spectroscopy

Data Source

PatentEP2531860B1Measuring multi-analyte samples using an in-line flow cell
Publication Date: 2018.04.11 BIO RAD LABORATORIES INC
  • EP2531860B1 patent drawingFigure 1A
  • EP2531860B1 patent drawingFigure 1B
  • EP2531860B1 patent drawingFigure 2

AI summary

Methods and systems for analyzing ratios of analytes within a flowing sample are provided. The flowing sample can be processed in real-time to determine a time interval over which a predetermined amount of a group of analytes passes by a fixed point in a flow cell. The predetermined amount can be routed to a sample container for future processing. The sample can comprise diluted blood and the analytes can comprise a component of hemoglobin, such as A1c, and the total amount of hemoglobin, of which the predetermined amount is metered.