Fluorescent Probe for Gadolinium Detection

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Solution Overview

Problem

Current methods for detecting gadolinium-based contrast agents (GBCA) in plasma are inadequate due to high cost, low sensitivity, and interference with pharmacokinetic profiles, making it difficult to conduct translational research, especially in small animal models where gadolinium is challenging to detect accurately.

Innovation Solution

A method involving a sensitized chelate complex, such as cs124-DTPA-Gd, where a light-absorbing sensitizer like carbostyril124 is bound to the chelator, allowing energy transfer to a signal-emitting compound like Terbium-DTPA, enabling detection of gadolinium through fluorescence or other spectroscopic means, even in non-luminescent states, facilitating accurate concentration measurement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If inductively-coupled-plasma mass spectrometry (ICP-MS) is used to detect gadolinium, then detection sensitivity is sufficient, but cost and measurement time increase significantly

Engineering Contradiction:

Improvedetection sensitivityVSAvoidcost and measurement time

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces a fluorescent probe as an intermediary substance that binds to gadolinium ions. This probe converts the non-luminescent gadolinium into a fluorescent signal that can be detected by standard fluorescence spectroscopy equipment, avoiding the need for expensive and complex ICP-MS instrumentation while maintaining adequate detection sensitivity

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the complex mechanical and chemical system of ICP-MS (inductively coupled plasma generation, mass spectrometry detection) with a simpler optical system based on fluorescence spectroscopy. This substitution uses light absorption and emission properties of the gadolinium-probe complex instead of ionization and mass-to-charge ratio measurement, significantly reducing equipment complexity and cost

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Device complexity

If relaxometry is used to detect gadolinium, then cost is reduced, but detection sensitivity becomes insufficient

Engineering Contradiction:

ImprovecostVSAvoiddetection sensitivity

Core Design Contradiction:

Device complexityVSMeasurement precision

Solution Approach 1:

The patent changes the detection parameter from magnetic relaxation properties (relaxometry) to optical fluorescence properties. By using a fluorescent probe that binds to gadolinium, the detection method transitions from measuring NMR signal relaxation to measuring fluorescence intensity, achieving both cost reduction and maintained sensitivity

Inventive Principle:

Principle #35Parameter changes

3Difficulty of detecting and measuring

If fluorescent labels are attached to GBCA for detection, then detection capability is improved, but plasma kinetics and biodistribution are affected

Engineering Contradiction:

Improvedetection capabilityVSAvoidplasma kinetics accuracy

Core Design Contradiction:

Difficulty of detecting and measuringVSReliability

Solution Approach 1:

The patent applies fluorescent labeling locally and selectively to the chelate portion of the GBCA molecule rather than modifying the entire contrast agent structure. This localized modification allows the gadolinium-chelate complex to maintain its original pharmacokinetic properties while the attached fluorescent probe provides detection capability

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent creates a fluorescent copy or surrogate of the GBCA molecule by attaching a fluorescent probe to the chelate. This fluorescent copy mimics the behavior of the original GBCA in plasma and tissues, allowing indirect measurement of GBCA kinetics through the fluorescent signal without significantly altering the original molecule's function

Inventive Principle:

Principle #26Copying

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

This approach provides a sensitive, cost-effective, and convenient method for detecting low concentrations of GBCA, reducing the need for large sample volumes and expensive equipment, allowing for accurate pharmacokinetic studies and rapid measurement of plasma kinetics parameters.

Implementation Method 1

energy transfer to a signal-emitting compound like Terbium-DTPA, enabling detection of gadolinium through fluorescence

Methodology Applied

Scientific EffectEnergy transfer:

Implementation Method 2

detecting the excited state of the substantially non-emitting metal by energy transfer to a second compound, which emits a signal when excited

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS10908141B2Methods and kits for detecting non-luminescent or weakly luminescent metals

Publication Date: 2021.02.02 NEW YORK UNIV

AI summary

The invention provides methods and kits for detecting the presence of, the amount of, or the concentration of a substantially non-emitting metal in a sample by a) providing a sensitizer to a chelator of the substantially non-emitting metal thereby creating a sensitized-metal complex; b) adding an unsensitized chelate, and c) detecting a signal from the unsensitized chelate. The substantially non-emitting metal may be gadoliniumn and may exist in complex with a chelator. The unsensitized chelate may be terbium (Tb) or europium (Eu) and the detecting a signal may be performed by fluorescence.