Amphipathic Lipid-Binding Protein Biosensor for Fatty Acid Detection

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Solution Overview

Problem

Current methods for monitoring free fatty acid (FFA) levels are inadequate for point-of-care settings due to the need for complex instrumentation, radiolabeled reagents, or enzyme-based assays that require strict controls, and are limited by the critical micelle concentration (CMC) of fatty acids, which restricts measurable concentrations and necessitates sample dilution.

Innovation Solution

Development of sensing elements and devices comprising amphipathic lipid-binding proteins or fatty acid binding proteins associated with luminescent reporter groups encapsulated in a hydrogel matrix with a co-monomer that inhibits micelle formation, allowing direct measurement of fatty acids without dilution and extending the dynamic range of detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If acrylodan-labeled fatty acid binding protein is used to measure fatty acid concentrations, then measurement is possible at low concentrations, but measurement is limited at concentrations above the CMC (critical micelle concentration) requiring sample dilution

Engineering Contradiction:

Improvefatty acid concentration measurementVSAvoidmeasurement range

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent modifies the physical-chemical parameters of the measurement system by incorporating co-monomers with specific properties (ionic, nonionic, hydrophobic, or hydrophilic) into the hydrogel matrix. These parameter changes alter the micelle formation behavior of fatty acids, enabling measurement across a broader concentration range from 0.01 mM to 1.5 mM without requiring sample dilution.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite hydrogel matrix system combining multiple components: the base hydrogel, amphipathic lipid-binding proteins with luminescent reporter groups, and co-monomers. This composite material integrates the binding specificity of proteins, the optical detection capability of luminescent groups, and the micelle-modulating properties of co-monomers to achieve extended measurement capabilities.

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If enzyme-based colorimetric assays are used for FFA monitoring, then quantification is achievable, but strict time and temperature controls are required increasing operational complexity

Engineering Contradiction:

ImproveFFA quantificationVSAvoidoperational simplicity

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces the enzyme-based colorimetric assay system with a luminescence-based detection system using amphipathic lipid-binding proteins associated with luminescent reporter groups. This substitution eliminates the need for enzyme reactions that require strict time and temperature controls, while maintaining accurate quantification capabilities through direct luminescence measurement.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If radiolabeled reagents are used for FFA measurement, then accurate quantification is possible, but complex instrumentation is required

Engineering Contradiction:

ImproveFFA quantification accuracyVSAvoidinstrumentation complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces radiolabeled reagent-based measurement with a luminescence-based detection system. This substitution eliminates the need for complex radiological instrumentation while maintaining accurate quantification through the use of amphipathic lipid-binding proteins associated with luminescent reporter groups that can be measured with standard luminescence detectors.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 accurate and direct measurement of fatty acid concentrations across a wider range (0.01 mM to 1.5 mM) without the need for sample dilution, improving monitoring capabilities in both in vitro and in vivo applications, particularly for clinical settings.

Implementation Method 1

Binding of the amphipathic lipid or fatty acid to the appropriate binding protein can produce at least one detectable change in the property of the luminescent reporter group

Methodology Applied

Scientific EffectLuminescence: Luminescence

Implementation Method 2

The binding proteins and luminescent reporter groups are encapsulated within a hydrogel matrix that comprises at least one co-monomer, wherein the co-monomer is present at a concentration that decreases or inhibits micelle formation of the amphipathic lipid

Methodology Applied

Scientific EffectMicelle formation inhibition: Surfactant

Data Source

PatentUS8389290B2Biosensor device for sensing amphipathic analytes

Publication Date: 2013.03.05 BECTON DICKINSON & CO

AI summary

The current invention relates to sensing elements and devices comprising at least one amphipathic lipid-binding protein or fatty acid binding protein, wherein the binding proteins are associated with a luminescent reporter group. The binding proteins and luminescent reporter groups are encapsulated within a hydrogel matrix that comprises at least one co-monomer, wherein the co-monomer is present at a concentration that decreases or inhibits micelle formation of the amphipathic lipid. Binding of the amphipathic lipid or fatty acid to the appropriate binding protein can produce at least one detectable change in the property of the luminescent reporter group.