Patient-Specific Blood Vessel Mimicry via BOEC Alignment
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Solution Overview
Problem
Current therapeutic approaches for vascular diseases are inadequate due to poor prediction of human pathophysiology and drug responses from animal models, and Organ-on-a-chip technology has not been effectively leveraged for vascular diseases due to a lack of physiologically-relevant in vitro models of personalized human tissues and organs.
Innovation Solution
A microfluidic device system that mimics a patient's blood vessel by using blood outgrowth endothelial cells (BOECs) isolated from the patient, which are easily obtained and aligned within the device's microfluidic channel, allowing for personalized vascular disease modeling and drug screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If animal models are used for vascular disease research, then therapeutic approaches can be developed, but the prediction of human pathophysiology and drug responses is poor
Solution Approach 1:
The patent creates in vitro models that copy human blood vessel structures and functions using patient-derived endothelial cells. These models replicate the specific pathophysiology of individual patients, providing reliable predictions of human response without requiring animal models.
Solution Approach 2:
The patent applies local quality by using patient-specific endothelial cells that have the specific properties and disease characteristics of the individual patient. Each model has the local quality of being tailored to match the specific patient's vascular biology, enabling personalized predictions.
2Reliability
If generic cell lines are used in microfluidic devices, then device complexity is reduced, but the models lack patient-specific disease characteristics
Solution Approach 1:
The patent performs preliminary action by pre-isolating and characterizing patient-specific endothelial cells before model creation. The cells are prepared and qualified in advance, then applied to the microfluidic device, streamlining the overall process while maintaining patient-specific relevance.
Solution Approach 2:
The patent changes the parameter of cell source from generic cell lines to patient-derived endothelial cells. This parameter change enables patient-specific disease modeling while the microfluidic platform provides a standardized framework that manages the complexity through systematic processing.
3Reliability
If exogenous stimulation is used to induce disease states, then model creation is simplified, but the models cannot predict natural disease progression
Solution Approach 1:
The patent applies self-service by using patient-derived cells that naturally express the disease characteristics. The cells themselves provide the disease phenotype through their inherent properties, eliminating the need for external stimulation to induce the disease state.
Solution Approach 2:
The patent incorporates feedback by using patient-specific cells that naturally respond to their disease state. The model captures the natural feedback loops and pathophysiological processes that occur in the patient's body, providing accurate predictions of disease progression without artificial intervention.
4Manufacturing precision
If blood outgrowth endothelial cells are isolated and aligned in microfluidic channels, then patient-specific vascular models are created, but the process requires precise cell alignment and coating
Solution Approach 1:
The patent replaces complex mechanical cell alignment procedures with the microfluidic flow field that naturally guides cell orientation. The flow conditions within the microfluidic channel automatically align the endothelial cells in the desired orientation, substituting mechanical manipulation with fluid dynamic control.
Solution Approach 2:
The patent changes the parameter of cell orientation from random to aligned through controlled flow conditions. By adjusting flow rate, shear stress, and residence time parameters, the system achieves uniform cell alignment and coating without complex mechanical processing.
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 system provides a disease-specific and patient-specific evaluation of vascular diseases, predicting in vivo pathophysiology and enabling personalized medical applications, overcoming the limitations of conventional models that rely on generic cell lines and require exogenous stimulation.
Implementation Method 1
a pump configured to withdraw a blood sample of the patient from a fluid conduit coupled to the fluid inlet of the microfluidic channel, and perfused the blood sample through the microfluidic channel
Implementation Method 2
combining the blood sample with a density gradient media, centrifuging the blood sample and the density gradient media to separate a form a distinct buffy layer
Implementation Method 3
centrifuging the blood sample and the density gradient media to separate a form a distinct buffy layer
Implementation Method 4
a majority of the plurality of BOECs are aligned with a flow axis of the microfluidic channel
Data Source
AI summary
A system for mimicking a blood vessel of a patient includes a microfluidic device including a body and a microfluidic channel formed in the body, wherein the microfluidic channel includes a fluid inlet and a fluid outlet, and a coating formed on the microfluidic channel including a plurality of blood outgrowth endothelial cells (BOECs) isolated from the patient and which define an inner surface of the microfluidic channel.