Optical Thermal Denaturation Profile for Protein Diagnostics

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Solution Overview

Problem

Current diagnostic methods for protein denaturation, such as Differential Scanning Calorimetry (DSC), are slow, not suitable for routine analysis of multiple biological samples, and primarily measure tertiary protein structure, failing to provide comprehensive denaturation profiles necessary for diagnosing a wide range of diseases.

Innovation Solution

A fast optical thermal method using fluorimetry or circular dichroism spectroscopy to obtain denaturation profiles of biological samples without dilution, incorporating fluorescent probes and multi-cuvette apparatus for simultaneous analysis, allowing diagnosis of pathologies by comparing profiles with reference data.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If DSC is used to obtain denaturation profiles of biological samples, then measurement precision is improved, but productivity deteriorates due to slow analysis speed and inability to process multiple samples routinely

Engineering Contradiction:
Improvedenaturation profile measurementVSAvoidanalysis speed and sample processing capacity
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent replaces the mechanical/thermal measurement system of DSC with an optical measurement system. Optical methods (fluorimetry, circular dichroism spectroscopy) are used to detect protein denaturation through changes in optical properties, enabling faster analysis and simultaneous processing of multiple biological samples without the adiabatic jacket constraints of DSC

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

Solution Approach 2:

The optical thermal denaturation method is designed to handle diverse biological samples (blood, plasma, serum) and detect multiple types of pathologies simultaneously. The system can analyze quaternary, tertiary, and secondary protein structures, providing comprehensive diagnostic capability for a wide range of diseases including brain diseases, inflammatory diseases, and cancer

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If DSC is used to study protein denaturation, then measurement precision for tertiary structure is improved, but adaptability deteriorates as it cannot comprehensively diagnose a wide panel of diseases

Engineering Contradiction:
Improvetertiary structure denaturationVSAvoiddiagnostic application range
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent measures multiple optical parameters (fluorescence intensity, circular dichroism signal, absorbance) across different wavelengths and temperature ranges to capture comprehensive protein structure information. This multi-parameter approach enables detection of changes in quaternary, tertiary, and secondary structures, expanding diagnostic capability beyond what single-parameter DSC can provide

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The optical thermal denaturation system is designed to diagnose a comprehensive panel of diseases by detecting protein structure changes associated with various pathologies. The method can identify brain diseases (neurodegenerative, cancer), inflammatory diseases, and other conditions through analysis of biological samples, making it universally applicable across multiple diagnostic domains

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If DSC apparatus is used for routine analysis, then measurement precision is maintained, but device complexity and operational difficulty increase due to adiabatic jacket requirements and non-replaceable cells

Engineering Contradiction:
Improveheat exchange recordingVSAvoidadiabatic jacket and cell replacement system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent eliminates the need for adiabatic jackets and non-replaceable cells by substituting optical measurement with thermal measurement. Optical methods can be performed in standard cuvettes without special thermal isolation, allowing routine analysis with simpler equipment and replaceable sample containers

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

Solution Approach 2:

The optical measurement system uses standard, replaceable cuvettes instead of expensive, non-replaceable DSC cells requiring adiabatic isolation. This enables routine disposal of single-use sample containers, simplifying operations and reducing maintenance requirements for routine biological sample analysis

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 rapid, comprehensive diagnosis of various pathologies, including brain diseases, by providing detailed protein denaturation profiles without the limitations of DSC, facilitating early detection and treatment adaptation.

Implementation Method 1

obtaining an optical thermal denaturation profile of said biological sample

Methodology Applied
Scientific EffectOptical spectroscopy: Absorption Spectroscopy

Implementation Method 2

the optical thermal denaturation profile is obtained by an optical method selected from the group consisting of fluorimetry, circular dichroism spectroscopy, infra-red spectroscopy and ultra-violet spectroscopy

Methodology Applied
Scientific EffectFluorimetry: Fluorescence

Implementation Method 3

circular dichroism (CD) spectroscopy, are also used for studying proteins denaturation

Methodology Applied
Scientific EffectCircular dichroism: Magnetic Circular Dichroism

Implementation Method 4

This process generally involves the application of some external stresses or compounds such as strong acids or bases, concentrated inorganic salts, organic solvents, radiations or heat

Methodology Applied
Scientific EffectThermal heating: Heating

Data Source

PatentEP3568691A1Optical thermal method and system for diagnosing pathologies
Publication Date: 2019.11.20 UNIV DAIX MARSEILLE

AI summary

The invention concerns a method and a system for diagnosing a pathology in a mammal in need thereof. The method according to the invention comprises the following steps: collecting a blood, blood plasma or blood serum sample from said mammal, said biological sample comprising a protein mixture; obtaining an optical thermal denaturation profile of said biological sample; comparing said optical thermal denaturation profile of said biological sample with an optical thermal denaturation reference profile; and diagnosing the pathology.