Enzymatic Biosensor for Direct Free Thyroid Hormone Quantification

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Solution Overview

Problem

Current methods for quantifying free thyroid hormones are imprecise and indirect, failing to distinguish between active and inactive hormones, which complicates the diagnosis of thyroid-related disorders.

Innovation Solution

A biosensor system utilizing immobilized iodothyronine deiodinases and anti-rT3 antibodies on a substrate, allowing for the direct quantification of free T3 and T4 in a single step by catalyzing specific enzymatic reactions, thereby enabling precise measurement of these hormones.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional immunoassays are used to measure thyroid hormones, then the diagnosis can be performed, but the measurement precision is poor and the method is indirect

Engineering Contradiction:
Improvemeasurement precisionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces conventional immunoassay methods with an enzymatic biosensor system that uses iodothyronine deiodinases to directly catalyze and detect free thyroid hormones. This enzymatic approach substitutes the indirect mechanical/chemical immunoassay process with a direct biochemical reaction that provides superior measurement precision while maintaining manageable device complexity through immobilized enzyme technology.

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

Solution Approach 2:

The patent introduces iodothyronine deiodinases as intermediary enzymes that specifically catalyze the deiodination of free T4 and T3 hormones. These enzymes act as mediators between the target analyte (free thyroid hormones) and the detection system, enabling direct and precise measurement while avoiding the indirectness of conventional immunoassays.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If indirect estimation methods are used for thyroid hormone measurement, then the diagnosis can be performed, but the reliability is reduced

Engineering Contradiction:
ImprovereliabilityVSAvoidloss of time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent employs preliminary action by immobilizing iodothyronine deiodinases on the sensor surface before sample introduction. This pre-prepared enzymatic system is ready to immediately catalyze the deiodination reaction upon contact with the sample, eliminating time-consuming separation steps and providing reliable direct measurement of free thyroid hormones in a single-step process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent extracts and measures only the free (active) form of thyroid hormones by using deiodinases that specifically act on unbound hormones. This selective extraction of the active hormone fraction from the complex blood matrix provides reliable diagnosis by focusing measurement on the clinically relevant free hormone portion, avoiding interference from bound hormones.

Inventive Principle:
Principle #2Taking out (Extraction)

3Ease of operation

If free thyroid hormones are not directly distinguished, then the measurement process is simplified, but the diagnostic value is reduced

Engineering Contradiction:
Improveease of operationVSAvoidloss of information
Core Design Contradiction:
Ease of operationVSLoss of information

Solution Approach 1:

The patent applies local quality by creating distinct measurement zones on the sensor that can differentiate between free and bound thyroid hormones. The immobilized deiodinases provide localized enzymatic activity that specifically processes free hormones, while the sensor structure maintains the ability to distinguish this local reaction from other components, preserving diagnostic information without complicating operation.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses iodothyronine deiodinases as intermediaries that specifically recognize and catalyze reactions with free thyroid hormones. This intermediary enzymatic system provides a clear distinction between free and bound hormones through selective catalysis, preserving critical diagnostic information about active hormone levels while maintaining ease of operation through a unified sensor platform.

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 approach provides a more accurate and specific method for diagnosing thyroid-related disorders by directly measuring free thyroid hormones, overcoming the limitations of existing indirect and imprecise techniques.

Implementation Method 1

The sensor comprises iodothyronine deiodinase, which catalyzes the following reactions: T4+H2O→T3+I−+2H+ +e− (EC 1.21.99.4); T3+H2O→T2+I−+2H+ +e− (EC 1.21.99.3)

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Implementation Method 2

In an enzyme sensor, for example, electrons generated by the reaction of a substrate contained in a sample liquid, i.e. an analyte, with an enzyme or the like reduce an electron acceptor and a measuring device electrochemically measures the amount of the reduced electron acceptor.

Methodology Applied
Scientific EffectElectrochemical transduction:

Data Source

PatentEP3775180B1Biosensor for diagnosis of thyroid dysfunction
Publication Date: 2022.01.12 AEGIRBIO AB
  • EP3775180B1 patent drawingFigure 1
  • EP3775180B1 patent drawingFigure 2
  • EP3775180B1 patent drawingFigure 3

AI summary

The present invention relates to a biosensor and applications thereof for the quantification of free thyroid hormones to evaluate thyroid function. Methods and tools for diagnosis of thyroid-related diseases are also disclosed herein.