Electro-cross-linking protein polyphenol biosensor

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Solution Overview

Problem

Existing protein-based biosensors face challenges with protein immobilization techniques, such as protein denaturation, leakage issues, and reduced enzymatic activity, which affect the accuracy and reliability of glucose measurements.

Innovation Solution

A liquid composition comprising a protein, a polyphenol, and a morphogen is used, where an electric stimulus is applied to form a solid composition of cross-linked protein and polyphenol on an electrochemical probe, enhancing protein stability and enzymatic activity while preventing leakage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If conventional covalent binding or cross-linking techniques are used to immobilize proteins, then protein stability increases, but enzymatic activity is reduced

Engineering Contradiction:

Improveprotein stabilityVSAvoidenzymatic activity

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The invention changes the chemical parameters of the cross-linking reaction by using glutaraldehyde vapor at controlled concentrations and temperatures, rather than liquid cross-linkers. This parameter change allows progressive cross-linking that stabilizes proteins while preserving enzymatic active sites, resolving the contradiction between stability and activity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention applies preliminary action by pre-equilibrating the protein solution with glutaraldehyde vapor before final immobilization. This preliminary exposure allows controlled modification of protein surface groups without denaturation, preparing the proteins for stable immobilization while maintaining activity

Inventive Principle:

Principle #10Preliminary action

2Ease of manufacture

If protein adsorption or entrapment techniques are used, then the immobilization process is simple, but protein leaking occurs

Engineering Contradiction:

Improveimmobilization simplicityVSAvoidprotein retention

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The invention replaces mechanical/physical immobilization methods (adsorption, entrapment) with chemical cross-linking using glutaraldehyde vapor. This substitution creates covalent bonds that firmly retain proteins on the support, eliminating leaking while maintaining procedural simplicity through vapor-phase treatment

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Ease of manufacture

If conventional manual cross-linking by drop- or dip-coating is used, then the process is straightforward, but reproducibility and control are poor

Engineering Contradiction:

Improveprocess simplicityVSAvoidimmobilization control

Core Design Contradiction:

Ease of manufactureVSManufacturing precision

Solution Approach 1:

The invention replaces manual liquid application (drop- or dip-coating) with automated vapor-phase cross-linking. The vapor diffusion process provides uniform distribution of glutaraldehyde throughout the protein solution, enabling precise control of cross-linking degree and improving reproducibility while maintaining ease of operation

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention introduces glutaraldehyde vapor as an intermediary medium that uniformly distributes cross-linker molecules throughout the protein solution. This vapor-phase intermediary ensures consistent exposure of all protein molecules to the cross-linker, improving control and reproducibility compared to localized liquid application

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

The method achieves excellent sensitivity and selectivity in glucose detection with reduced enzyme leakage and increased stability, suitable for miniaturized biosensors and biofuel cells.

Implementation Method 1

applying an electric stimulus to the electrochemical probe so as to form a solid composition comprising the cross-linked product of a protein and a polyphenol

Methodology Applied

Scientific EffectElectro-oxidation: Oxidation

Implementation Method 2

The Applicants have developed a concept named morphogenic electrotriggered self-construction of films, based on electro-cross-linking between two polymers in one pot using a morphogen

Methodology Applied

Scientific EffectElectrodeposition: Electrodeposition

Implementation Method 3

A morphogen is a molecule or an ion that is produced at an interface and diffuses into the solution, thus creating a concentration gradient and locally inducing a chemical reaction or interaction between two non-interacting species

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 4

electro-cross-linking between two polymers in one pot using a morphogen

Methodology Applied

Scientific EffectElectro-cross-linking: Chemical Bonding

Data Source

PatentEP3543347B1Method of electro-cross-linking a protein with a polyphenol for the manufacture of a biosensor

Publication Date: 2023.09.06 UNIVERSITY OF STRASBOURG

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Figure 3~3b

AI summary

The present invention relates to a liquid composition comprising a protein, a polyphenol and a morphogen; to a solid composition comprising the cross-linked product of a protein and a polyphenol; to a biosensor and a biofuel cell comprising said solid composition bound to a surface of an electrochemical probe; to a process for the detection of an analyte with said biosensor; and to the use of a ferrocene as a morphogen in an electrodeposition process.