Microfluidic Tissue Barrier Models Without Membrane Separation
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Solution Overview
Problem
Existing systems for modeling tissue barriers using plastic membranes hinder physiologically relevant interactions between cells and other elements, such as antagonists or agonists, by blocking the tissue interface.
Innovation Solution
A method of creating tissue models using a microfluidic device with stop-flow polymerization, where solutions containing scaffold materials and cells are laminarly flowed into a channel, polymerized, and monitored with an electrode array to map electrical impedance without a semi-permeable membrane.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Weight of moving object
If plastic membranes are used to separate cell types in culture, then cell separation is achieved, but cell interaction with antagonists or agonists is blocked
Solution Approach 1:
The invention removes the plastic membrane barrier from the system entirely. Instead of using a membrane to separate cell types, the patent employs microfluidic channels to physically separate different cell populations while maintaining an open interface that allows small molecules, peptides, and nucleic acids to freely interact with cells on both sides of the interface.
Solution Approach 2:
The invention introduces a cell-adherent coating as an intermediary layer on the channel surface. This coating enables cell attachment and barrier formation without requiring a physical membrane, thus mediating between the need for cell separation and the need for molecular interaction.
2Reliability
If semi-permeable membranes are used to create tissue barriers, then barrier formation is achieved, but the tissue interface is blocked preventing interaction of cells and other elements
Solution Approach 1:
The invention replaces the mechanical membrane barrier with a biologically-based barrier formed by cells adhering to a coated surface in a microfluidic channel. This substitution eliminates the need for physical membranes while maintaining barrier function through cellular mechanisms.
Solution Approach 2:
The invention changes the fundamental parameter of barrier formation from material-based (membrane) to biology-based (cellular). By altering how the barrier is created and maintained, the system achieves both barrier integrity and interface accessibility simultaneously.
3Stability of the object's composition
If membrane-based tissue barrier models are used, then tissue separation is maintained, but physiologically relevant interactions are prevented
Solution Approach 1:
The invention applies different properties to different regions of the system: the channel surface is coated to promote cell adhesion and barrier formation, while the channel lumen remains open to allow free molecular interaction. This local differentiation enables both stable tissue structure and physiological relevance.
Solution Approach 2:
The invention creates a composite system combining microfluidic channel structure, cell-adherent coating, and living cell layers. This composite approach achieves both structural stability and physiological functionality that neither membranes nor cells alone could provide.
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
This approach enables real-time, high-throughput analysis of cell interactions and barrier integrity, mimicking in vivo conditions by allowing direct cell contact and eliminating the need for membrane separation, facilitating pharmaceutical development and drug testing.
Implementation Method 1
polymerizing the scaffold with a polymerization method; activating flow of a third solution in the first channel, second channel, or both; and stopping the flow of the third solution. The scaffold material of the second solution can be polymerized with light (for example UV)
Implementation Method 2
allowing the first and the second solution to flow into the flow channel through laminar flow
Implementation Method 3
mapping the electrical impedance of the flow channel with the plurality of electrode pairs before, during, or after the flow
Data Source
AI summary
Described herein are two-dimensional (2D) models of tissue barriers, methods of making and using the same, and on-model analysis techniques. Aspects of the present disclosure include systems and methods relating to microfluidic tissue models, in particular those of the vasculature-endothelial barrier. Systems and methods as described herein can utilize impedance mapping to assess model conditions in response to stimuli, for example the introduction of pharmaceutical compositions.