Test Element with Spatially Resolved Reference Area

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Solution Overview

Problem

Existing methods for determining analyte concentration in physiological samples require irreversible binding of the analyte to the test carrier, limiting their applicability and precision, especially with small sample volumes, and often suffer from background signal issues due to non-wetted reference areas having different optical properties.

Innovation Solution

A system utilizing a test element with a detection area containing reaction and reference areas, where the reference area maintains unchanged absorption behavior upon wetting, allowing for spatially resolved detection and evaluation of light intensities without analyte binding, using a geometric arrangement or barrier to prevent sample contact and employing enzymes and reagents that form water-insoluble dyes to prevent diffusion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a reference area is used for referencing in optical measurements, then technical effects such as properties of the light source or detector can be compensated for, but the background signal for referencing has different optical properties than the area wetted with the sample when the reference area is not wetted by the sample

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidoptical properties consistency
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The detection area is divided into different zones with distinct functions: a reaction area containing reagents for analyte detection and a reference area without reagents. Both areas are wetted by the sample, ensuring they share identical optical properties while serving different measurement purposes. The reference area provides a baseline signal for compensation without suffering from the optical property mismatch that occurs when reference areas remain dry.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If binding partners are fixed to the carrier to bind the analyte, then the analyte concentration can be determined, but the analyte must bind to the binding partner and diffusion is no longer possible, limiting the analysis to bound molecules only

Engineering Contradiction:
Improveanalyte determinationVSAvoidanalyte type coverage
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

Enzymes are introduced as intermediary substances in the reaction area that catalyze reactions with the analyte to produce colored products. These enzymes remain immobilized on the carrier while allowing free-diffusing analyte molecules to access them. This intermediary mechanism enables detection of both bound and free analyte molecules, expanding the versatility of the assay beyond what is possible with direct binding partners alone.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If the detection area is miniaturized to reduce sample volume requirements, then smaller sample volumes can be used, but the signal strength decreases and measurement precision is reduced

Engineering Contradiction:
Improvesample volumeVSAvoidsignal strength
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The detection area is segmented into multiple reaction areas and reference areas, each contributing to the overall signal. This segmentation allows for parallel processing of the sample and provides multiple measurement points that can be averaged or compared, thereby maintaining measurement precision even when the total detection area is miniaturized to require smaller sample volumes.

Inventive Principle:
Principle #1Segmentation

4Measurement precision

If reagents are applied to the detection area to react with the analyte, then the analyte concentration can be determined through color change, but the reagents may diffuse and cause background signal in reference areas

Engineering Contradiction:
Improveanalyte detectionVSAvoidbackground signal
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

Reagents are applied selectively only to the reaction areas where they are needed for analyte detection, while the reference areas remain free of reagents. This localized application prevents reagent diffusion from causing background signals in the reference areas, as the reference areas serve purely as optical references without any chemical reactions occurring within them.

Inventive Principle:
Principle #3Local quality

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

Enables precise determination of analytes with small sample volumes by minimizing changes in absorption behavior in the reference area, improving measurement accuracy and reducing errors in miniaturized systems, while avoiding the need for additional referencing and ensuring comparable diffusion processes across the detection area.

Implementation Method 1

reaction areas with reagents for detecting the analyte, which cause a change in absorption behavior when reacting with the analyte

Methodology Applied
Scientific EffectAbsorption behavior change: Absorption (EM radiation)

Implementation Method 2

employing enzymes and reagents that form water-insoluble dyes to prevent diffusion

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 3

detection unit for the spatially resolved detection of light intensities that are received by the detection area

Methodology Applied
Scientific EffectReflection: Reflection

Implementation Method 4

the at least one reference area is designed in such a way that the absorption behavior does not change substantially when it is wetted

Methodology Applied
Scientific EffectAbsorption stability: Absorption (EM radiation)

Data Source

PatentEP1936362B1Test element with referencing
Publication Date: 2020.03.18 ROCHE DIABETES CARE GMBH
  • EP1936362B1 patent drawingFigure 1a~1b
  • EP1936362B1 patent drawingFigure 2a~2b

AI summary

The device has detection region (2) in a test element (1) which contains a reaction region (3) with reagents for detecting an analyte. The analyte causes a change in the absorption behavior upon reaction with the analyte. The detection region contains a reference region (4) in which the absorption behavior is not changed by the analyte. A detection unit (7) is provided for the spatially resolved detection of light intensities. The reaction regions and the reference regions are arranged alternately in two dimensions. An independent claim is also included for a method for manufacturing a test element for determining analyte in a liquid.