Microfluidic Perfusion Device with Constriction for Tissue Viability
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Solution Overview
Problem
Current methods for preserving tissue samples ex vivo are limited by diffusion-limited mass transport, leading to reduced viability and inability to accurately model in vivo responses to medical interventions, necessitating a more effective means of nutrient and oxygen delivery.
Innovation Solution
A device with a channel comprising a constriction is used to perfuse biological samples, allowing for advective flow that enhances the delivery and penetration of oxygen and substances, maintaining sample viability and enabling more realistic in vivo-like studies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tissue samples are cultured while submerged in culture media with diffusion-based mass transport, then the samples can be preserved ex vivo, but the delivery of nutrients and oxygen is limited beyond 100 μm due to diffusion constraints, resulting in reduced explant viability
Solution Approach 1:
The patent applies hydraulic principles by implementing a microfluidic device that uses pressure-driven flow to perfuse culture media through the tissue sample. The device includes channels with constrictions that generate sufficient pressure differential to drive fluid flow through the tissue, replacing diffusion-based transport with convection-based transport. This hydraulic approach enables deep penetration of nutrients and oxygen throughout the entire tissue volume, resolving the limitation of diffusion-based delivery beyond 100 μm.
2Duration of action of stationary object
If tissue samples are preserved ex vivo without vascular perfusion, then the samples can be maintained for study, but mass transport is restricted to diffusion through the tissue surface, leading to reduced viability and insignificant response to external stimuli
Solution Approach 1:
The microfluidic device implements hydraulic flow through channels that interface with the tissue sample's vascular structure. By applying pressure gradients, the system achieves perfusion that mimics in vivo conditions, enabling both extended ex vivo survival and appropriate physiological responses to stimuli. The pressure-driven flow ensures continuous delivery of nutrients and removal of waste products throughout the tissue.
Solution Approach 2:
The patent changes the mass transport parameter from diffusion-dominated to convection-dominated by introducing pressure-driven flow. This parameter change transforms the transport mechanism, enabling deep tissue penetration and sustained viability. The flow rate and pressure parameters are controlled to optimize nutrient delivery while maintaining tissue integrity during ex vivo preservation.
3Ease of manufacture
If conventional diffusion-based culture methods are used, then the setup is simple, but the mass transport limitations prevent accurate modeling of in vivo responses to medical interventions
Solution Approach 1:
The microfluidic device uses hydraulic flow mechanisms to achieve perfusion that accurately models in vivo conditions. The pressure-driven flow through channels with constrictions recreates physiological flow patterns, enabling precise measurement of tissue responses to medical interventions. This approach maintains relative simplicity while dramatically improving the accuracy of in vivo response modeling compared to diffusion-based methods.
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 method achieves longer preservation of tissue samples and more accurate modeling of in vivo responses by ensuring deeper penetration of nutrients and substances, thereby improving the viability and relevance of ex vivo studies.
Implementation Method 1
This method provides quicker delivery and deeper penetration of oxygen and substances in a biological sample
Implementation Method 2
mass transport is exclusively restricted to diffusion, through the tissue surface
Data Source
AI summary
The present application relates to methods for perfusing a biological sample in a device comprising a channel comprising a constriction wherein the method comprises flowing a liquid through the channel, sealing the channel with the biological sample and maintaining a flow of liquid within the biological sample. The application also relates to a method for assaying a substance, a device for use in perfusing a biological sample and a method of manufacturing a device.