Time-Resolved Fluorescence Detection of Warfarin Concentration

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Solution Overview

Problem

Current methods for monitoring warfarin, a vitamin K antagonizing anticoagulant, are indirect and lack sensitivity, particularly in self-monitoring, due to its high binding to human serum albumin and the narrow therapeutic window, making it challenging to determine its concentration accurately in patient blood samples.

Innovation Solution

A method and apparatus utilizing time-resolved fluorescence spectroscopy to measure the fluorescence lifetime and intensity of warfarin in a sample, allowing for the direct detection and quantification of warfarin bound to proteins or free in plasma, enabling efficient monitoring of its effect on blood coagulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If indirect methods (prothrombin time measurement) are used to monitor warfarin, then the method is easier to operate, but the measurement precision and sensitivity are insufficient

Engineering Contradiction:

Improveease of operationVSAvoidmeasurement precision

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent replaces the indirect mechanical/chemical clotting time measurement method with direct optical fluorescence detection. The fluorescence lifetime and intensity measurements provide direct quantification of warfarin concentration, eliminating the need for clotting time assays and achieving both high precision and ease of operation through automated optical measurement.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent utilizes changes in fluorescence lifetime and intensity parameters of warfarin to directly measure drug concentration. By monitoring these optical parameters, the system achieves sensitive and precise detection without relying on indirect clotting time measurements, thereby improving measurement precision while maintaining operational simplicity.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If fluorescence lifetime and intensity measurements are performed to determine warfarin concentration, then the measurement precision is improved, but the device complexity increases

Engineering Contradiction:

Improvemeasurement precisionVSAvoiddevice complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs optical fluorescence measurement techniques to directly detect warfarin concentration with high precision. The use of fluorescence lifetime and intensity measurements provides accurate drug level detection, while the optical-based approach replaces complex mechanical or chemical assay systems, ultimately achieving a balance between precision and manageable device complexity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If direct fluorescence detection of warfarin is implemented, then the sensitivity is improved, but the difficulty of detecting and measuring increases due to protein binding

Engineering Contradiction:

ImprovesensitivityVSAvoiddifficulty of detecting and measuring

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent exploits changes in fluorescence lifetime parameters of warfarin based on its binding state. By measuring fluorescence lifetime rather than just intensity, the method can distinguish between bound and free warfarin, thereby improving sensitivity and overcoming the measurement difficulties posed by protein binding through parameter differentiation.

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

This approach provides a robust and sensitive method for determining warfarin concentration, improving accuracy in monitoring its therapeutic window and coagulation effects, facilitating precise dosage adjustments and individualized treatment.

Implementation Method 1

irradiating the sample with light from a light source for exciting the anticoagulant through its absorption of the light, the excitation of the sample resulting in a fluorescent emission from the sample

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 2

exciting the anticoagulant through its absorption of the light

Methodology Applied

Scientific EffectAbsorption of light: Absorption (EM radiation)

Implementation Method 3

measuring means arranged to measure the fluorescent emission from the sample

Methodology Applied

Scientific EffectFluorescent emission detection: Fluorescence

Data Source

PatentUS8841633B2Method and apparatus for detecting pharmaceuticals in a sample

Publication Date: 2014.09.23 NICHOLLS IAN A

AI summary

A method and apparatus for measuring a vitamin K antagonizing anticoagulant present in a sample (116), arranged to: irradiate (304) the sample (116) with light from a light source (114) for exciting the anticoagulant through its absorption of the light, the excitation of the sample (116) resulting in a fluorescent emission from the sample (116); measure (306) the fluorescent emission from the sample (116); determine (308) a fluorescence lifetime (T1) of the fluorescent emission of the sample (116); determine (310) an intensity (A1) of the fluorescent emission at the fluorescence lifetime (T1); and determine (312) a amount (c) of the anticoagulant, as a function of the intensity (A1) of the fluorescent emission at the fluorescence lifetime (T1).