Microfluidic Stress Emulation for Thrombogenic Risk Assessment

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for monitoring thrombogenic risk in patients with mechanical circulatory support devices, such as ventricular assist devices, are limited by their inability to accurately assess anti-thrombotic drug efficacy under dynamic flow and shear conditions, leading to ineffective prevention of device-associated thrombosis and associated complications like stroke and death.

Innovation Solution

Development of microfluidic devices that replicate the shear stress profiles of mechanical circulatory support devices, allowing for patient-specific and device-specific monitoring of thrombogenic potential by modeling and emulating the shear stress profiles of these devices in a lab-on-chip system, enabling point-of-care assessment of platelet activation and anti-thrombotic drug efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If central lab-based testing systems are used to examine anti-platelet agent efficacy, then drug efficacy can be assessed, but the testing conditions do not represent the actual flow and shear conditions in patients during VAD use

Engineering Contradiction:
Improveaccuracy of anti-thrombotic drug efficacy assessmentVSAvoidapplicability to actual in vivo flow and shear conditions
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically varying flow rate, shear stress magnitude, and exposure duration in the microfluidic device to match in vivo conditions. The device enables dynamic adjustment of shear stress parameters (e.g., 100-500 dynes/cm²) and flow conditions to replicate the physiological environment patients experience during VAD operation, thereby improving the accuracy and applicability of drug efficacy assessments

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a simplified copy of the complex in vivo environment using a microfluidic chip that replicates key hemodynamic parameters. The device copies the essential flow patterns, shear stress profiles, and platelet exposure conditions of actual VAD operation on a miniaturized platform, enabling accurate testing without requiring actual in vivo conditions or large laboratory apparatus

Inventive Principle:
Principle #26Copying

2Measurement precision

If large laboratory-based apparatuses are used for measuring anti-thrombotic therapy efficacy, then measurements can be obtained, but the systems are not amenable to rapid bedside use

Engineering Contradiction:
Improvecapability to measure platelet activation stateVSAvoidportability for bedside monitoring
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts the essential measurement function from large laboratory apparatus and concentrates it into a miniaturized microfluidic device. The core capability to measure platelet activation state is isolated and implemented in a portable chip format that can be operated at the bedside, eliminating the need for large equipment while preserving measurement precision

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces complex mechanical laboratory apparatus with a microfluidic system that uses integrated micro-pumps and micro-channels. This substitution enables the system to be compact, portable, and suitable for bedside operation while maintaining the ability to generate controlled shear stress and flow conditions for accurate platelet activation measurement

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Ease of manufacture

If existing testing systems operate under static conditions or minimal blood agitation, then testing can be performed, but they do not examine anti-thrombotic drug efficacy under actual blood flow and shear conditions

Engineering Contradiction:
Improvesimplicity of testing procedureVSAvoidrelevance to actual thrombogenic risk in VAD patients
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent implements dynamic flow conditions in the microfluidic device, where blood flow rate, shear stress, and exposure duration can be continuously adjusted during the assay. The system transitions from static or minimal agitation to dynamic, controllable flow patterns that replicate actual VAD operation, thereby improving the reliability and clinical relevance of the results while maintaining procedural simplicity through automated control

Inventive Principle:
Principle #15Dynamics

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 microfluidic system effectively monitors thrombogenic risk and assesses anti-thrombotic drug efficacy under conditions mimicking actual device use, reducing the likelihood of thrombosis and enhancing patient safety by providing personalized and device-specific thrombogenic risk assessment.

Implementation Method 1

modeling the shear stress profile of platelets flowing through a pathology

Methodology Applied
Scientific EffectShear stress: Shear Stress

Implementation Method 2

flowing a sample from the subject through the microfluidic device

Methodology Applied
Scientific EffectFluid flow:

Data Source

PatentEP3186006B1Methods for microfluidic stress emulation
Publication Date: 2021.05.26 POLITECNICO DI MILANO
  • EP3186006B1 patent drawingFigure 1
  • EP3186006B1 patent drawingFigure 2
  • EP3186006B1 patent drawingFigure 3

AI summary

Provided herein is technology relating to microfluidic devices and particularly, but not exclusively, to devices, methods, systems, and kits for imparting stresses on a fluid flowing through a microfluidic device that is designed to mimic a stress profile of a macrofluidic device or pathology.