Analytical Instrument Reagent Arrangement for Glucose Measurement

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Solution Overview

Problem

Existing glucose sensors in whole blood measurements are influenced by blood cell concentration, leading to delayed and inaccurate results due to the time it takes for glucose to diffuse from blood cells to serum, especially at high hematocrit levels, and variations in measurement results caused by reagent solubility issues when measurement time is shortened.

Innovation Solution

An analytical instrument with a specific arrangement of reagent portions and an electron detection medium, where the reagent portion containing an electron mediator is positioned upstream and dissolves when the sample enters, ensuring electron transfer is complete before reaching the detection medium, and an oxidoreductase is used to facilitate electron transfer from glucose in blood cells to serum, reducing the impact of blood cell concentration and enhancing measurement reproducibility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If measurement time is shortened to improve productivity, then glucose consumption in blood serum increases rapidly, but the ratio of glucose transferred from blood cells to serum decreases, worsening measurement accuracy

Engineering Contradiction:
Improvemeasurement speedVSAvoidmeasurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The reagent portion is divided into multiple functional layers: a first reagent layer containing oxidoreductase for rapid glucose oxidation, and a second reagent layer containing electron mediator for electron transfer. This segmentation allows the reaction to proceed in stages, with glucose first being oxidized in the upstream layer and electrons transferred in the downstream layer, enabling accurate measurement even at short measurement times.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The oxidoreductase layer is positioned upstream to perform preliminary oxidation of glucose before the electrons reach the electron mediator layer. This preliminary action ensures that glucose from blood cells is rapidly oxidized and electrons are generated early in the flow path, allowing sufficient time for electron transfer even when overall measurement time is shortened.

Inventive Principle:
Principle #10Preliminary action

2Ease of manufacture

If reagent portion has poor solubility to reduce manufacturing complexity, then oxidoreductase and electron mediator do not disperse uniformly, worsening measurement precision

Engineering Contradiction:
Improvereagent portion fabricationVSAvoidmeasurement reproducibility
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

Different regions of the reagent portion are assigned different solubility characteristics: the oxidoreductase layer uses water-soluble or readily dispersible reagents to ensure uniform distribution in the aqueous blood sample, while the electron mediator layer may use differently soluble reagents optimized for electron transfer. This local quality differentiation ensures both ease of manufacture and measurement precision.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The reagent portion employs composite material structures combining multiple reagents with different solubility profiles. The oxidoreductase is combined with water-soluble carriers or surfactants to ensure uniform dispersion, while the electron mediator is combined with appropriate carriers to maintain stability and functionality. This composite approach resolves the contradiction between manufacturing simplicity and measurement precision.

Inventive Principle:
Principle #40Composite materials

3Device complexity

If electron mediator is positioned downstream closer to detection medium to simplify device structure, then electron transfer from glucose in blood cells is incomplete, worsening measurement accuracy

Engineering Contradiction:
Improvereagent arrangementVSAvoidglucose measurement accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The detection system is segmented into distinct functional zones: an upstream oxidoreductase layer for glucose oxidation, a downstream electron mediator layer for electron transfer, and a separate detection medium. This segmentation ensures sufficient spatial distance for complete electron transfer from glucose in blood cells while maintaining a relatively simple overall device structure through functional zonation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The electron mediator acts as an intermediary substance that facilitates electron transfer from the oxidation products of glucose to the detection medium. By positioning this intermediary layer downstream but at an optimized distance, the system allows complete electron transfer to occur while maintaining device simplicity through the use of this mediating substance.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 arrangement allows for accurate and rapid glucose measurement by ensuring electron transfer from glucose in blood cells to serum before reaching the detection medium, reducing the influence of blood cell concentration and improving reproducibility, especially at high hematocrit levels and in low concentration ranges.

Implementation Method 1

the reagent portion contains an electron mediator for supplying an electron taken from glucose in the sample to the electron detection medium

Methodology Applied
Scientific EffectElectron transfer: Redox Reactions

Implementation Method 2

electrons can be quickly taken from the glucose existing in blood serum (blood plasma) by oxidoreductase

Methodology Applied
Scientific EffectEnzymatic oxidation: Enzyme

Implementation Method 3

to take electrons from the glucose existing in blood cells requires longer time than to take electrons from the glucose existing in blood serum

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 4

the transfer of glucose from blood cells to blood serum (blood plasma) is not the simple diffusion due to the difference of glucose level between inside and outside of blood cells but the facilitated diffusion which depends on the glucose transmission ability of blood cell membranes

Methodology Applied
Scientific EffectFacilitated diffusion: Diffusion

Data Source

PatentUS7780828B2Analytical instrument having improved arrangement of reagent section and analytical method
Publication Date: 2010.08.24 ARKRAY INC
  • US7780828B2 patent drawing
  • US7780828B2 patent drawing
  • US7780828B2 patent drawing

AI summary

The present invention relates to an analytical instrument (1) which includes a flow path (5) for moving a sample containing blood cells, an introduction port (50) for introducing the sample into the flow path (5), a reagent portion (51) arranged in the flow path (5), and an electron detection medium (52) for obtaining information necessary for analyzing an analysis target component contained in the sample in relation with an amount of electrons transferred. The reagent portion (51) contains an electron mediator for supplying an electron taken from the analysis target component in the sample to the electron detection medium (52), and at least part of the reagent portion is positioned adjacent to the introduction port (50).