Small-Size NIR Fluorophores for Microbial Pathogen Detection
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Solution Overview
Problem
Conventional near-infrared (NIR) fluorescent labels are bulky and possess stable positive charges, which hinder their affinity to targets and cellular uptake, making them unsuitable for effective detection of microbial pathogens in body tissues.
Innovation Solution
Development of small-size NIR fluorophores, such as derivatives of DDAO, with improved spectral properties and bioconjugation capabilities, allowing for precise imaging of microbial targets using Fluorescent Molecular Tomography (FMT).
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional NIR fluorescent labels are used, then detection sensitivity is improved due to reduced background noise, but targeting affinity and cellular uptake are hindered due to bulky size and stable positive charge
Solution Approach 1:
The patent changes the key parameters of the NIR fluorophore structure by removing stable charged groups and reducing molecular size. This allows the label to maintain detection sensitivity while improving targeting affinity and cellular uptake, directly resolving the contradiction between measurement precision and reliability
Solution Approach 2:
The patent extracts and removes the problematic stable positive charge groups from the conventional NIR fluorescent labels. By taking out these charged groups that cause steric hindrance and electrostatic repulsion, the label achieves better cell membrane penetration and target binding while retaining NIR fluorescence properties
2Quantity of substance
If conventional NIR fluorescent labels are used, then solubility is enhanced through charged groups, but interaction with target and cell permeability are affected
Solution Approach 1:
The patent changes the solubility parameter by using small neutral groups instead of large charged groups. This allows the NIR label to maintain adequate solubility for biological applications while significantly improving cell permeability and target interaction, resolving the contradiction between quantity of substance and ease of operation
Solution Approach 2:
The patent uses small, transient neutral groups that provide sufficient solubility during the labeling process but do not persist as bulky charges that would hinder cellular uptake. These small groups fulfill their solubility function without creating long-term steric or electrostatic barriers
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 small-size NIR fluorophores preserve targeting properties and enhance light-emission properties, enabling effective detection and imaging of microbial pathogens in body tissues, offering a superior alternative to radionuclides in diagnostic applications.
Implementation Method 1
Fluorescence Molecular Tomography (FMT) is a powerful approach to image microbial infections in body tissues. It is based on using fluorescently labeled compounds that recognize pathogen-specific targets, thereby rendering the pathogen cells fluorescent after binding to the targets.
Implementation Method 2
In FMT, imaging of fluorescent material (labeled microbial pathogens) in body is achieved through excitation by powerful light source and detection of the induced fluorescence.
Data Source
AI summary
The present invention provides compounds useful as novel near-infrared labels, compositions containing these compounds, and methods of using the near-infrared labels to identify targets in vitro, in situ and in vivo. The invention also provides small or large molecule conjugates between targeting agents and NIR labels, as well as methods and kits thereof, that can be used in diagnostics and treatment of diseases related to microbes in mammalian animals.