Fixed Endothelial Monolayer for Thrombosis Diagnostics
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Solution Overview
Problem
Current diagnostic and monitoring devices for thrombosis-related functions do not accurately capture the physiological interplay between endothelial cells, platelets, and shear stress, leading to unreliable assessments, especially in clinical settings, due to the difficulty in maintaining living endothelial cells and the inability to mimic physiologically relevant conditions such as pulmonary thrombosis.
Innovation Solution
A microfluidic device lined with a chemically fixed human endothelium that retains its ability to modulate hemostasis under continuous flow, allowing for the formation of platelet-rich thrombi in the presence of physiological shear, and a lung-on-a-chip device with primary alveolar cells to study pulmonary blood clotting and platelet-endothelial interactions, using a stochastic analytical method to quantify dynamics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If living endothelial cells are used to line microfluidic devices, then the ability to modulate hemostasis and capture physiological interplay is improved, but the difficulty in maintaining cell viability and robustness deteriorates
Solution Approach 1:
The patent creates a fixed endothelial cell monolayer that replicates the functional properties of living endothelial cells without requiring their maintenance. The fixed cells preserve the ability to modulate hemostasis and interact with platelets under flow conditions, eliminating the need for continuous cell culture maintenance while retaining physiological relevance
Solution Approach 2:
The patent transforms the state of endothelial cells from living to fixed through chemical fixation, changing their physical and biological parameters. This fixation process preserves the cells' ability to bind platelets and modulate hemostasis while eliminating metabolic requirements and viability concerns, enabling long-term storage and repeated use
2Ease of operation
If current diagnostic devices are used without endothelial cells, then the ease of operation is improved, but the measurement precision of thrombosis-related functions deteriorates
Solution Approach 1:
The fixed endothelial cell monolayer serves as a stable, reproducible model that can be manufactured and stored, providing consistent measurement conditions across different tests and laboratories. This eliminates the variability associated with living cell cultures while maintaining the physiological interactions needed for accurate thrombosis function assessment
Solution Approach 2:
The endothelial cells are pre-fixed and prepared in advance under controlled conditions, allowing standardization of the assay platform. This preliminary preparation ensures that the endothelial surface is ready for immediate use with patient samples, combining the physiological accuracy of endothelial cells with the operational simplicity of pre-prepared diagnostic kits
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 provides a more reliable and accurate measurement of thrombus formation and platelet function, capable of simulating organ-level functionality, enabling better drug development and clinical diagnostics by mimicking human pulmonary thrombosis and reducing reliance on animal models.
Implementation Method 1
stimulating the fixed endothelial cell monolayer to induce formation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample
Data Source
AI summary
A method is directed to determining a thrombosis function and includes flowing a fluid sample over a surface having a fixed endothelial cell monolayer. The method further includes stimulating the fixed endothelial cell monolayer to induce formation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample. In response to the clot formation, the method further includes determining a thrombosis function associated with the fluid sample and the fixed endothelial cell monolayer.