Dye-Based Liquid Reagent Volume Indicator for Assay Bias Correction

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Solution Overview

Problem

Existing diagnostic assays face inaccuracies and biases due to incomplete delivery of assay buffer in reaction vessels, leading to increased reagent concentrations and reduced accuracy and repeatability of results.

Innovation Solution

An analytical reaction kit with a sealed reaction cassette and a liquid reagent container featuring a flexible cover, where the buffer is dispensed gravitationally, and a dye like Naphthol Green B is used to correct for volume variations and interference, ensuring accurate analyte concentration measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If assay buffer is dispensed using a pull tab mechanism, then the buffer can be released from the buffer tray into the reaction vessel, but a portion of the assay buffer adheres to the tab and is removed from the reaction vessel, resulting in incomplete delivery of the predetermined buffer volume

Engineering Contradiction:
Improvebuffer volume deliveryVSAvoidbuffer loss to tab
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The harmful element (adhering buffer on the tab) is extracted and accounted for separately. The system measures the volume of buffer that adheres to the tab and uses this information to correct the final analyte concentration calculation, rather than attempting to prevent the adhesion itself.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system incorporates a feedback mechanism where the volume of buffer delivered is measured (via dye concentration detection), and this measurement is fed back to correct the final analyte concentration result. This closed-loop approach compensates for the buffer loss to the tab.

Inventive Principle:
Principle #23Feedback

2Quantity of substance

If the pull tab is pulled firmly and slowly to ensure complete buffer delivery, then more buffer is delivered to the reaction vessel, but this requires additional time-consuming steps and is subject to user-introduced errors

Engineering Contradiction:
Improvebuffer volume deliveryVSAvoidbuffer dispensing time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The system performs self-measurement and self-correction. The analyzer automatically detects the dye concentration to determine buffer volume delivered and automatically applies the correction factor to the analyte concentration, eliminating the need for manual timing or user technique control.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The mechanical user action of pulling the tab with specific force and speed is replaced by an automated detection system using optical measurement of dye concentration, which objectively and consistently measures the actual buffer volume delivered regardless of user technique.

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

3Quantity of substance

If automated puncturing or centrifugation is used to ensure complete buffer delivery, then buffer delivery is improved, but the device complexity and process steps increase

Engineering Contradiction:
Improvebuffer volume deliveryVSAvoidbuffer dispensing mechanism
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The complex mechanical systems (automated puncturing devices, centrifugation mechanisms) are extracted and replaced with a simpler approach: a pull tab mechanism combined with optical detection of dye concentration to measure and correct buffer volume.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system changes from controlling buffer delivery through mechanical parameters (force, speed, puncture depth) to controlling and measuring buffer delivery through chemical parameters (dye concentration in the delivered buffer), which can be detected optically and used for correction.

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If reagent concentration is increased due to incomplete buffer delivery, then the assay sensitivity may improve, but the accuracy and repeatability of diagnostic results decrease due to bias

Engineering Contradiction:
Improveanalyte concentration measurementVSAvoidassay result accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The system uses feedback from dye concentration measurement to determine the actual buffer volume delivered and applies a correction factor to the analyte concentration result. This closed-loop feedback ensures accurate results regardless of variations in buffer delivery volume.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system intentionally allows for partial buffer delivery (including loss to the tab) and then applies a mathematical correction to achieve the accurate result, rather than attempting to achieve perfect buffer delivery through complex mechanical means.

Inventive Principle:
Principle #16Partial or excessive action

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 solution significantly reduces biases and improves the precision of analyte concentration measurements by accurately delivering the buffer and accounting for dye interference, enhancing the reliability of diagnostic assays.

Implementation Method 1

a dye like Naphthol Green B is used to correct for volume variations and interference

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 2

the buffer is dispensed gravitationally

Methodology Applied
Scientific EffectGravitation: Gravitation

Data Source

PatentEP3934807B1Dye-based liquid reagent volume indicator for use in analyte detection assays
Publication Date: 2024.12.25 SIEMENS HEALTHCARE DIAGNOSTICS INC
  • EP3934807B1 patent drawingFigure 1
  • EP3934807B1 patent drawingFigure 2
  • EP3934807B1 patent drawingFigure 3A

AI summary

Non-limiting embodiments of a modified devices that comprise at least one dye for determining whether results obtained from the conductance of at least one diagnostic assay are biased, as well as kits and methods of use related thereto.