Liquid Thromboplastin Reagent Stability via Segmentation and Chelation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current liquid thromboplastin reagents have limited stability and shelf life, and freeze-dried versions require significant preparation time, introducing variability in prothrombin time measurements.
Innovation Solution
A two-part kit with separate containers for thromboplastin tissue factor and calcium, where a chelator is included in the tissue factor component to extend shelf life by protecting against divalent metal ion-dependent deterioration, allowing for immediate mixing and use, thereby reducing preparation time and increasing stability to at least 2-5 years.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid thromboplastin reagent is prepared in a single vial with all components, then convenience of use is improved, but shelf life is limited to no greater than 1 year
Solution Approach 1:
The reagent system is divided into separate components: a lyophilized thromboplastin powder in a first container and a liquid solvent containing calcium ions in a second container. This segmentation allows each component to be optimized independently - the thromboplastin remains stable in lyophilized form while the calcium solution is prepared separately, extending overall shelf life beyond 1 year while maintaining ease of use through simple mixing at the time of use.
2Duration of action of stationary object
If freeze-dried thromboplastin is used, then shelf life is extended, but preparation time is significantly increased and measurement precision is reduced
Solution Approach 1:
The calcium ions are pre-prepared in a stable liquid solvent solution that can be stored separately for extended periods. This preliminary preparation eliminates the need for time-consuming reconstitution procedures associated with traditional freeze-dried thromboplastin, as the calcium solution is ready to use immediately upon mixing with the lyophilized thromboplastin powder, reducing preparation time while maintaining extended shelf life.
3Reliability
If calcium ions are included in the thromboplastin solution, then coagulation function is enabled, but divalent metal ion-dependent deterioration occurs
Solution Approach 1:
The system segments calcium ions into a separate liquid solvent component rather than including them directly with the thromboplastin powder. This separation prevents divalent metal ion-dependent deterioration of the thromboplastin while maintaining coagulation function, as calcium ions are introduced only when needed at the time of use through simple mixing of the two components.
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 solution significantly extends the shelf life of liquid thromboplastin reagents, reduces preparation time, and minimizes variability in prothrombin time measurements by preventing divalent metal ion-dependent instability, ensuring consistent performance over extended storage periods.
Implementation Method 1
a chelator is included in the tissue factor component to extend shelf life by protecting against divalent metal ion-dependent deterioration
Implementation Method 2
The prothrombin time (PT) is used with patient plasmas to determine either naturally occurring deficiencies in the extrinsic pathway of blood coagulation
Data Source
Figure 1A
Figure 1B
Figure 1C
AI summary
What is described is a kit for preparing a liquid thromboplastin reagent for a prothrombin time assay. The kit simplifies and minimizes reagent preparation time and is stable for 2-5 years.