Urea Biosensor Protein Binding Signal Transduction

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing urea detection methods are sensitive to inhibition and require multiple reagents or complex detectors, making them unreliable and cumbersome for practical applications.

Innovation Solution

Development of biosensors comprising a urea-binding protein with a reporter group that produces a detectable signal upon urea binding, allowing for rapid, reliable, and accurate urea detection without additional substrates or complex measurements, and maintaining functionality even after immobilization, desiccation, and extended storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If enzyme-based assays with urease are used to detect urea, then urea concentration can be measured, but the assay becomes sensitive to inhibition and requires multiple reagents or complex detectors

Engineering Contradiction:
Improveassay reliabilityVSAvoiddetector complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the urea detection function from complex enzyme-based systems and implements it through a simplified protein-binding approach. The urea-binding protein directly interacts with urea to produce a detectable signal, eliminating the need for urease enzymes and multiple reagents, thus reducing device complexity while maintaining reliability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The biosensor system is designed to be self-sufficient, where the urea-binding protein performs both the detection and signal generation functions. The system does not require external substrates or complex measurement mechanisms, allowing it to operate autonomously and simplifying the overall device architecture

Inventive Principle:
Principle #25Self-service

2Measurement precision

If multiple reagents and complex detectors are used in urea detection, then measurement capability is achieved, but the system becomes cumbersome for practical applications

Engineering Contradiction:
Improveurea detection accuracyVSAvoidpractical applicability
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent segments the detection system into a single functional unit - the urea-binding protein that performs binding and signal generation in one component. This segmentation eliminates the need for multiple separate reagents and complex detectors, making the system easier to operate while maintaining measurement precision

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the fundamental detection parameter from enzymatic reaction products (requiring multiple reagents) to direct protein-ligand binding events. This parameter change simplifies the operational procedure while preserving accurate urea concentration measurement capability

Inventive Principle:
Principle #35Parameter changes

3Productivity

If conventional biosensors are used, then urea detection is possible, but they require additional substrates or measurement of substrate consumption rates

Engineering Contradiction:
Improvedetection speedVSAvoidmonitoring mechanism complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The urea-binding protein serves itself by directly converting urea binding into a detectable signal without requiring external substrates. The protein's conformational change upon urea binding is directly measured, eliminating the need to monitor substrate consumption or product generation rates, thus simplifying the monitoring mechanism while maintaining high detection speed

Inventive Principle:
Principle #25Self-service

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 biosensors provide precise, reliable, and instantaneous urea detection in various samples, including complex fluids, with reduced costs and simplified handling, enabling widespread applicability in clinical, industrial, and environmental settings.

Implementation Method 1

The ligand comprises urea: and the ligand-binding protein includes a domain or region(s) of the protein that binds the urea. The domain or region involved in ligand binding is comprised of a plurality of residues, e.g., non-contiguous amino acids of the ligand-binding protein, which are contact points or sites of contact between the ligand and its cognate ligand-binding protein.

Methodology Applied
Scientific EffectLigand binding:

Implementation Method 2

The binding of urea to the urea-binding domain of the urea-binding protein causes a change in signaling by the reporter group. A reporter group that transduces a detectable signal may be attached to the urea-binding proteins (biosensors) described herein.

Methodology Applied
Scientific EffectSignal transduction:

Implementation Method 3

In embodiments, detectable signal comprises a fluorescent, electrochemical, nuclear magnetic resonance (NMR), or electron paramagnetic resonance (EPR) signal.

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3377904B1Urea biosensors and uses thereof
Publication Date: 2024.05.01 DUKE UNIV
  • EP3377904B1 patent drawingFigure 1A~1D
  • EP3377904B1 patent drawingFigure 2A~2B
  • EP3377904B1 patent drawingFigure 3

AI summary

The present subject matter provides urea biosensors as well as compositions, devices, and methods comprising such biosensors.