Direct Thrombin Inhibitor Detection in Serum via Exogenous Thrombin

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Solution Overview

Problem

Current methods for detecting direct thrombin inhibitors are limited by the need for citrate plasma samples, which require separate blood withdrawals, leading to risks of side effects and influencing test results due to varying coagulation protein quantities, and are not applicable for clinical routine analysis in serum samples.

Innovation Solution

A method involving mixing a sample containing a direct thrombin inhibitor with a composition containing thrombin and a chromogenic substrate, allowing the thrombin to release a detectable substance, which is then measured, without the need for citrated plasma, enabling detection in serum or other non-plasma samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If citrate plasma samples are used for detecting direct thrombin inhibitors, then the detection method is reliable, but separate blood withdrawals are required leading to side effects and increased complexity

Engineering Contradiction:

Improvedetection reliabilityVSAvoidsample collection complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention makes the thrombin inhibitor detection method universally applicable to multiple sample types (serum, plasma, urine, other body fluids) rather than being limited to citrate plasma only. This is achieved by using exogenously added thrombin and chromogenic substrates that work across different sample matrices, eliminating the need for separate coagulation tubes and reducing sample collection complexity while maintaining detection reliability

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If separate blood withdrawals for coagulation analysis are performed, then thrombin inhibitor concentration can be measured, but risks of side effects and patient discomfort increase

Engineering Contradiction:

Improvethrombin inhibitor concentration measurementVSAvoidside effects from blood withdrawal

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention merges the thrombin inhibitor detection with routine clinical chemistry analysis by allowing both to be performed on the same serum sample. This integration eliminates the need for separate blood withdrawals for coagulation analysis, reducing patient discomfort and side effects while maintaining precise measurement of thrombin inhibitor concentrations through the use of exogenous thrombin and chromogenic substrates

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If citrate plasma is used for thrombin inhibitor determination, then coagulation proteins are available for the reaction, but the method is not applicable for clinical routine analysis in serum

Engineering Contradiction:

Improvethrombin inhibitor determination accuracyVSAvoidsample type applicability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention introduces exogenously added thrombin as an intermediary that provides the necessary coagulation enzyme activity in serum samples where endogenous thrombin is absent or inactive. This intermediary thrombin reacts with chromogenic substrates to produce detectable signals, enabling accurate thrombin inhibitor determination in serum and other body fluids without requiring citrate plasma, thus expanding method applicability while maintaining determination accuracy

Inventive Principle:

Principle #24Intermediary (Mediator)

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 method allows for efficient detection of direct thrombin inhibitors in serum or urine samples, reducing the risk of side effects associated with blood withdrawals and providing a more reliable measurement by eliminating the need for separate coagulation tubes, thus overcoming the limitations of existing protocols.

Implementation Method 1

the colorant para-nitroaniline is released by an exogenously added coagulation enzyme (e.g. thrombin) from a chromogenic substrate

Methodology Applied

Scientific EffectChromogenic substrate cleavage: Hydrolysis

Implementation Method 2

the activity/concentration of thrombin inhibitors or substances inhibiting thrombin being measured in a concentration-dependent manner. The result is a linear or sigmoidal decrease of the release of para-nitroaniline, measured at 405 nanometers in the photometer

Methodology Applied

Scientific EffectAbsorption spectroscopy: Absorption Spectroscopy

Data Source

PatentUS9944971B2Determination of direct thrombin inhibitors in fluids like serum or urine

Publication Date: 2018.04.17 DOASENSE

AI summary

The present invention relates to a method for detecting at least one direct thrombin inhibitor in a sample other than citrate plasma, comprising the step of mixing a sample containing a thrombin inhibitor with a composition containing thrombin under conditions which allow the thrombin to release a detectable substance from a chromogenic substrate.