Protein Sensing Molecule Analyte Detection

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Solution Overview

Problem

Current biosensors for analytes like glutamine and glucose rely on enzymes or expensive instrumentation, and there is a need for improved proteins and methods for characterizing samples with enhanced sensitivity and specificity.

Innovation Solution

Development of protein sensing molecules with a first detectable quality that changes concentration-dependent upon analyte binding and a second quality that remains unchanged, allowing for precise sample characterization using a method that includes contacting the protein with the sample and measuring these qualities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If enzyme-based biosensors are used for analyte detection, then detection capability is achieved, but additional reagents and complex instrumentation are required

Engineering Contradiction:
Improvedetection capabilityVSAvoidinstrumentation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts and utilizes the natural conformational change capability inherent in binding proteins, removing the need for enzyme-based catalytic reactions and additional reagents. The binding protein itself performs the detection function through its intrinsic structural transition upon analyte binding, eliminating complex enzymatic systems and reducing instrumentation requirements.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The binding protein serves multiple functions: it binds the analyte specifically, undergoes conformational change for signal generation, and can be labeled with various detectable groups. This multi-functionality replaces the need for separate enzyme components and reagents required in traditional enzyme-based biosensors.

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

2Ease of manufacture

If conventional binding proteins are used as sensors, then reagent-free operation is achieved, but detection sensitivity and specificity need improvement

Engineering Contradiction:
Improvereagent-free operationVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The invention introduces detectable labels at specific local positions on the binding protein that are strategically chosen to maximize the detectable signal upon conformational change. This localized labeling approach enhances detection sensitivity while maintaining the reagent-free advantage of binding proteins.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention modifies the binding protein by introducing detectable labels, thereby changing its physical parameters to enable enhanced detection. The labeled binding protein maintains its natural binding and conformational change properties while gaining improved detectability through the attached labels.

Inventive Principle:
Principle #35Parameter changes

3Device complexity

If single detectable quality changes are used for analyte detection, then simplicity is maintained, but measurement accuracy and reliability are limited

Engineering Contradiction:
Improvesensor simplicityVSAvoidmeasurement accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The invention segments the detectable signal into multiple independent qualities (e.g., fluorescence intensity, wavelength shift, lifetime) that can be measured simultaneously. This segmentation allows for ratiometric or multi-parameter detection, improving measurement accuracy while maintaining the simplicity of using a single labeled binding protein.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from single-parameter detection to multi-dimensional detection by utilizing multiple detectable qualities or parameters from the labeled binding protein. This dimensional expansion enables more accurate and reliable measurements through cross-validation and reduced susceptibility to artifacts.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 approach enables sensitive and specific detection of analytes, reducing the need for additional reagents and expensive equipment, and provides a robust method for characterizing samples with high accuracy.

Implementation Method 1

The key event that accompanies molecular recognition between a binding protein and its substrate is a conformational change

Methodology Applied
Scientific EffectConformational change:

Implementation Method 2

analyte-binding proteins may be used as sensor proteins to characterize samples

Methodology Applied
Scientific EffectAnalyte binding:

Data Source

PatentUS7718353B2Proteins, sensors, and methods of characterizing analytes using the same
Publication Date: 2010.05.18 UNIV OF MARYLAND BALTIMORE COUNTY
  • US7718353B2 patent drawing
  • US7718353B2 patent drawing
  • US7718353B2 patent drawing

AI summary

A protein sensing molecule is capable of binding an analyte in a sample. The protein sensing molecule includes a first detectable quality that changes in a concentration dependent manner when the protein sensing molecule is bound to the analyte. The protein sensing molecule also includes a second detectable quality that does not undergo substantial change when the protein sensing molecule is bound to the analyte. The protein sensing molecule may be used in methods for characterizing samples and may also be used in sensors.