Microfluidic Culture Plate With Semipermeable Membrane for ALI Co-Culture
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Solution Overview
Problem
Conventional microfluidic devices face challenges in efficiently culturing different types of cells and co-culturing cells, particularly in seeding cells onto membranes with smaller pore sizes, which affects the seeding process and overlap region of microfluidic channels, and lack robust preclinical models for evaluating therapeutic agents against respiratory viruses.
Innovation Solution
A microfluidic cell culturing device with a semipermeable membrane and chamber configuration that allows for high-throughput culturing of various tissue types, including adherent and suspension cells, in an air-liquid interface (ALI) format, enabling co-culture and measurement of tissue barrier function through transepithelial electrical resistance (TEER) measurements, and accommodating 3D printed and multilayer cultures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional microfluidic devices are used for cell culturing, then device simplicity is maintained, but cell seeding efficiency onto membranes with smaller pore sizes deteriorates
Solution Approach 1:
The device is divided into distinct layers including a bottom layer with microfluidic channels, a membrane layer with controlled pore sizes, and a top layer with a culture chamber. This segmentation allows each layer to be optimized independently - the membrane layer can use smaller pore sizes for better cell seeding efficiency while the overall device structure remains relatively simple to manufacture
Solution Approach 2:
The invention transitions from a planar microfluidic device to a three-dimensional stacked structure with multiple layers separated by a membrane. This dimensional change creates distinct compartments (channel layer, membrane layer, chamber layer) that can be independently optimized, allowing small pore sizes in the membrane for improved cell seeding while maintaining device simplicity through modular layering
2Productivity
If membranes with smaller pore sizes are used for cell culturing, then cell seeding performance is improved, but device complexity in the overlap region of microfluidic channels increases
Solution Approach 1:
The device separates the membrane functionality into a dedicated membrane layer that is distinct from the channel and chamber layers. This segmentation allows the membrane to have optimized small pore sizes for cell seeding without complicating the channel design, as each layer can be manufactured and assembled independently
Solution Approach 2:
The membrane layer serves multiple functions: it acts as a support structure for cell seeding, provides a barrier between the channel and chamber, and enables controlled permeability. This multi-functionality reduces the need for additional components in the overlap region, thereby reducing device complexity while maintaining improved cell seeding performance
3Productivity
If high-throughput culturing format is implemented, then productivity is improved, but device complexity increases
Solution Approach 1:
The stacked device design with bottom layer, membrane layer, and top layer creates a universal platform that can accommodate multiple cell types and culturing conditions within a single device structure. The standardized layer configuration enables high-throughput applications while maintaining relatively simple manufacturing through repeated assembly of the same modular components
Solution Approach 2:
By segmenting the device into standardized layers, the invention enables parallel production and assembly of multiple devices using the same components. This modular approach supports high-throughput culturing formats while keeping individual device complexity manageable through repetition of proven layer designs
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 high-throughput, human primary airway epithelial cell-based platform for modeling influenza and coronavirus infections, allowing for rapid assessment of therapeutic efficacy using a 96-well instrumented plate, and improves the accuracy of preclinical models by mimicking human respiratory barrier tissues.
Implementation Method 1
The membrane layer comprising a semipermeable membrane that forms at least a portion of a surface of the first channel
Implementation Method 2
measurement of tissue barrier function through transepithelial electrical resistance (TEER) measurements
Data Source
AI summary
The present disclosure describes systems and methods for providing culturing of a number of various tissue types in an air-liquid configuration in a high-throughput format and allowing co-culture of cells as well as application of physiologically relevant flow. A microfluidic cell culturing device is provided that includes a first channel having a first inlet port and a second inlet port, the first channel defined in a first layer. The microfluidic cell culturing device includes a membrane layer having a first surface coupled to the first layer defining the first channel, the membrane layer comprising semipermeable membrane that forms at least a portion of a surface of the first channel. The microfluidic cell culturing device includes a chamber defined in a second layer that exposes a portion the membrane layer to an external environment, wherein the chamber overlaps a portion of the first channel across the membrane layer.