Microfluidic Device for Real-Time Whole Blood Coagulation Monitoring
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Solution Overview
Problem
Current coagulation monitoring technologies are inadequate for real-time, quantitative assessment of whole blood coagulation, particularly in clinical settings, due to variability in sample preparation, user expertise, and failure to account for fluid dynamics, leading to inaccurate and unreliable measurements.
Innovation Solution
A microfluidic device with rectangular microchannels that mimics blood vessels, capable of operating in constant flow or pressure modes, incorporating shear stress and gradients to measure thrombotic potential and platelet aggregation in real-time, using phenomenological mathematical models to predict patient-specific clotting times.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional coagulation tests (PT, ACT, APTT) are used, then coagulation time can be measured, but measurement precision and reliability are poor due to variability in sample preparation, anticoagulation tubes, activators, equipment, and user expertise
Solution Approach 1:
The invention divides the coagulation testing process into discrete microfluidic channels with specific geometries (e.g., stenotic regions, varying widths) that create controlled flow conditions. Each channel segment serves a specific function (e.g., activation zone, measurement zone), eliminating the need for complex manual sample preparation and activator addition while maintaining measurement precision.
Solution Approach 2:
The invention changes the testing parameters by implementing controlled flow rates, pressure gradients, and shear stress conditions within the microfluidic device. These parameter changes standardize the testing environment, eliminating variability from manual操作流程 while maintaining accurate coagulation time measurements.
2Reliability
If static coagulation tests are performed, then clotting characteristics can be measured, but reliability is limited because platelet and endothelial cell functions are highly sensitive to physical forces including pressure and flow
Solution Approach 1:
The invention uses hydraulic principles to create controlled flow conditions within microfluidic channels. Pressure gradients and flow rates are precisely regulated to mimic physiological conditions, enabling reliable assessment of platelet and endothelial cell functions under realistic physical forces without excessive system complexity.
Solution Approach 2:
The invention transitions from static to dynamic testing by implementing controlled blood flow through microfluidic channels with varying geometries. The system dynamically adjusts flow rates and pressure to create physiological shear stress conditions, significantly improving the reliability of coagulation assessments while maintaining manageable device complexity through standardized microfluidic design.
3Measurement precision
If microfluidic devices with controlled flow are used, then measurement precision and physiological relevance are improved, but device complexity increases
Solution Approach 1:
The invention designs microfluidic devices that can perform multiple coagulation test functions within a single integrated platform. The device can simultaneously conduct different coagulation assessments under various flow conditions, reducing the need for multiple separate devices and procedures while maintaining high measurement precision.
Solution Approach 2:
The invention creates simplified microfluidic models that replicate key physiological features (e.g., vessel stenosis, branching patterns) without requiring full anatomical complexity. These copied physiological structures provide sufficient realism for accurate coagulation monitoring while keeping the device design manageable and scalable.
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
Provides accurate, real-time monitoring of whole blood coagulation under physiological conditions, improving clinical assessment and integration with extracorporeal blood perfusion systems, reducing variability and enhancing the specificity and sensitivity of coagulation monitoring.
Implementation Method 1
A pump to apply a constant differential pressure across the first port is provided
Implementation Method 2
incorporating shear stress and gradients to measure thrombotic potential
Data Source
Figure 1
Figure 2A~2B
Figure 3A~3D
AI summary
In accord with one aspect, a microfluidic coagulation assessment device defining a plurality of microchannels is provided, wherein a blood sample is driven through the microchannels at a substantially constant flow rate and a controller is configured to, in combination with a timer and a pressure sensing device, determine a first pressure value (or flow value) at an initiation of flow, a first time (Tpg) at which a second pressure value is about twice the determined first pressure value, and a second time (Tpf) at which a third pressure value is about (1+e) times the determined first pressure value and establish a subject coagulation model predictive of channel occlusion therefrom. In another aspect, the blood sample is driven through the microchannels at a substantially constant pressure and a controller is configured to, in combination with a timer and a flow sensing device, a first flow rate value at a first time corresponding to an initiation of flow, a second time (Tqg) at which a second flow rate value is determined to be about twice the determined first flow rate value, a third time (Tqf) at which a third flow rate value is determined to be about (1+e) times the determined first flow rate value, and a subject coagulation model predictive of channel occlusion.