Stackable Microfluidic BBB Model with Segmented Chambers
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Solution Overview
Problem
Current in vitro models for the blood-brain barrier (BBB) fail to accurately replicate the complex structure and function of the BBB, particularly in terms of shear-flow induced polarization and cell type support, leading to limitations in drug and toxin penetration studies and disease modeling.
Innovation Solution
A planar layered microfluidic device with stacked chambers and porous membranes allows for independent perfusion of both sides of the BBB model, supporting multiple cell types and enabling electrical recordings, while minimizing fluid volumes and optimizing shear flow conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If transwell models are used to study BBB, then cell types can be cultured, but fluid volumes are large and dilute signaling molecules
Solution Approach 1:
The device is divided into multiple stacked microfluidic layers, each containing separate chambers for different cell types. This segmentation allows independent control of fluid volumes in each chamber, enabling small physiologically relevant volumes that concentrate signaling molecules while maintaining distinct cellular compartments for accurate BBB modeling.
Solution Approach 2:
The invention transitions from traditional 2D transwell culture to a three-dimensional stacked microfluidic architecture. Multiple layers are stacked vertically, creating distinct chambers separated by porous membranes. This dimensional change enables precise control of fluid volumes in each chamber while maintaining cell-type specificity and physiological relevance.
2Reliability
If transwell models are used to study BBB, then cell types can be cultured, but shear-flow induced polarization is lacking
Solution Approach 1:
The device incorporates microfluidic channels that deliver controlled fluid flow across the endothelial cell layer. This hydraulic system generates physiological shear stress that induces polarization and mature tight junction formation in endothelial cells, accurately replicating in vivo BBB conditions without requiring complex external equipment.
Solution Approach 2:
The invention integrates cell culture chambers, fluid flow channels, and porous membrane separators into a single stacked microfluidic device. This merging of functions allows simultaneous cultivation of multiple cell types with controlled shear flow application, achieving physiologically relevant tight junction formation within a compact structure.
3Adaptability or versatility
If transwell models are used to study BBB, then barrier function can be studied, but electrical recordings are not possible
Solution Approach 1:
The stacked microfluidic device is designed with multi-functionality, serving as both a cell culture platform and an electrical recording system. Transparent porous membranes allow electrical signals from neurons to pass through to recording electrodes, while maintaining barrier function for studying drug penetration. This universal design enables simultaneous physiological and electrical measurements.
Solution Approach 2:
The device uses thin transparent porous membranes as separators between chambers. These thin films are electrically permeable, allowing electrical recordings of neural activity through the barrier, while maintaining physical separation and selective permeability for studying BBB transport functions.
4Adaptability or versatility
If transwell models are used to study BBB, then barrier structure can be modeled, but multiple cell types cannot be supported
Solution Approach 1:
The device is segmented into multiple stacked layers, each containing chambers for different cell types. This segmentation allows independent culture of endothelial cells, astrocytes, pericytes, and neurons in physiologically relevant volumes, enabling complex BBB modeling with multiple interacting cell types without requiring large fluid volumes.
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 solution provides a more faithful in vitro BBB model that supports mature tight junction formation, leukocyte extravasation, and real-time neuroelectric and metabolomic characterization, enhancing the understanding of BBB function and drug responses.
Implementation Method 1
The top through hole is sealed by the top cover and the top membrane to form a top chamber... The bottom through hole is sealed by the top membrane and the bottom substrate to form a bottom chamber... the top chamber and the bottom chamber correspond to each other and are separated by the top membrane
Data Source
AI summary
In certain aspects of the invention, a stackable device includes multiple elements stacked sequentially. A chamber is formed in each of the elements or between adjacent two of the elements, and each chamber is in fluid communication with an input channel and an output channel. The chambers are aligned with each other, and adjacent two chambers are separated from each other by a membrane. In certain aspects of the invention, a system includes at least one stackable device, each stackable device having multiple chambers; and at least one of a perfusion controller, a microformulator, and a microclinical analyzer in fluid communication with the at least one stackable device. In other aspects of the invention, the use of four microformulators, electrodes and an impedance analyzer can measure the impedance spectrum of each barrier in a multi-transwell plate.