Fluorescent Imaging Agents for Bacterial Infection Detection

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Solution Overview

Problem

Current diagnostic methods for bacterial infections are time-consuming, insensitive, and unreliable, particularly in distinguishing infection from sterile inflammation, and existing imaging techniques fail to accurately detect bacterial infections in vivo due to nonspecificity and sensitivity issues.

Innovation Solution

Development of fluorescent imaging agents that bind anionic surfaces on bacterial and apoptotic cells, comprising a positively charged moiety linked to a fluorophore, allowing for in vivo imaging of bacteria in live animals with enhanced specificity and sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional diagnostic methods (culture analysis) are used to detect bacterial infections, then detection can be performed, but the process is time-consuming and insensitive

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddiagnosis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces conventional mechanical culture-based diagnostic methods with optical imaging technology. Fluorescent probes emit light signals that can be detected and imaged in real-time, eliminating the need for time-consuming bacterial culture processes while significantly improving detection sensitivity and providing rapid diagnostic information.

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

Solution Approach 2:

The patent utilizes fluorescent probes that exhibit color changes or fluorescence emission when they bind to bacterial targets. These optical signal changes enable rapid visualization and detection of bacterial infections through imaging systems, providing both speed and sensitivity improvements over conventional methods.

Inventive Principle:
Principle #32Color changes

2Reliability

If anatomic imaging techniques (MRI, CT) are used to detect infections, then imaging can be performed, but they cannot consistently distinguish infection from sterile inflammation

Engineering Contradiction:
Improvediagnosis reliabilityVSAvoidinfection detection specificity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent employs fluorescent probes with multiple functional capabilities: they can bind to specific bacterial components (such as cell walls or membranes) while also providing optical imaging signals. This dual functionality enables specific targeting of bacteria while allowing differentiation from sterile inflammation through the unique binding pattern and signal characteristics of the probes.

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

Solution Approach 2:

The patent uses probes with specific local properties tailored for bacterial targeting. The probes are designed with molecular structures that specifically recognize and bind to bacterial components, providing localized and specific detection at the infection site while maintaining the ability to distinguish from non-infected tissues through targeted binding patterns.

Inventive Principle:
Principle #3Local quality

3Measurement precision

If radiolabeled antibiotics and peptides are used for imaging, then bacterial targeting can be achieved, but specificity and sensitivity remain suboptimal

Engineering Contradiction:
Improvebacterial detection sensitivityVSAvoidimaging specificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent optimizes multiple parameters of the fluorescent probes including molecular structure, fluorescence wavelength, binding affinity, and probe concentration. By carefully adjusting these parameters, the probes achieve both high sensitivity for detecting low bacterial loads and high specificity for distinguishing bacterial infections from other conditions, overcoming the limitations of radiolabeled agents.

Inventive Principle:
Principle #35Parameter changes

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 agents provide accurate and efficient detection and quantification of bacterial infections, improving diagnosis and treatment outcomes by visualizing bacterial sites with high specificity and sensitivity, aiding in the understanding of pathogenesis and infection processes.

Implementation Method 1

optical probes can be designed as dynamic molecular imaging agents that may alter their reporting profiles in vivo to provide molecular and functional information in real time. In order to achieve maximum penetration and sensitivity in vivo, the choice for most optical imaging in biological systems is within the red and near-infrared (NIR) spectral region (600-900 nm)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

The cell surface of bacteria are highly negatively charged, more so than healthy mammalian cells. Positively-charged cationic probes can be used to selectively target and bind the anionic surfaces of bacterial cells over healthy mammalian cells.

Methodology Applied
Scientific EffectElectrostatic attraction: Electrostatics

Data Source

PatentEP2831264B1Bacterial imaging agents and methods of using same
Publication Date: 2019.07.10 VISEN MEDICAL INC
  • EP2831264B1 patent drawingFigure 1A
  • EP2831264B1 patent drawingFigure 1B
  • EP2831264B1 patent drawingFigure 2A

AI summary

The invention provides a family of agents that target bacterial infection, which can be used as imaging agents or therapeutic agents. The agents can be used to image sites of bacterial infection as well as other physiological processes in a subject.