Microfluidic Neuronal Cell Culture Device for Innervated Models
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Solution Overview
Problem
Conventional cell culture techniques for reconstructing biological tissues in vitro lack innervation, preventing interactions between cultured cells and neuronal cells, which is essential for testing neurotoxic effects and other neuronal-related responses.
Innovation Solution
A cell culture device with a microfluidic layer and feed well system that allows for the growth of neuronal cells and their axons in a compartmentalized environment, enabling interaction with biological tissues like skin models, facilitating the creation of innervated in vitro models.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional cell culture techniques are used to reconstruct biological tissues in vitro, then the tissue structure can be formed, but the tissue lacks innervation and cannot interact with neuronal cells
Solution Approach 1:
The device is divided into distinct compartments: a first chamber for neuronal cells, a second chamber for biological tissue, and a microfluidic layer connecting them. This segmentation allows independent cultivation of different cell types while enabling controlled interaction through the microfluidic channels, resolving the contradiction between interaction capability and structural complexity.
Solution Approach 2:
The microfluidic layer acts as an intermediary between the neuronal cell chamber and the biological tissue chamber. It contains channels that guide axonal growth from neuronal cells to the tissue while maintaining physical separation between the two cell types, enabling interaction without direct mixing and thus managing complexity.
2Reliability
If a compartmentalized microfluidic structure is implemented to enable neuronal cell growth and tissue interaction, then innervated in vitro models can be created, but the device complexity increases
Solution Approach 1:
The microfluidic layer provides locally optimized conditions for axonal growth with channels having specific geometries and biochemical coatings in the regions where neuronal processes need to extend. This localized functional differentiation enables reliable neuro-toxicity testing while keeping the rest of the device structure manageable.
Solution Approach 2:
The microfluidic layer is positioned between and connects the two chambers, with channels nested within the layer structure. This nested arrangement allows the complex microfluidic network to be integrated within the overall device architecture without excessive external complexity, maintaining reliability while managing structural complexity.
3Ease of manufacture
If conventional in vitro models without innervation are used, then the models are simpler to produce, but they cannot assess neurotoxic effects or provide complete physiological responses
Solution Approach 1:
The device enables preliminary cultivation of neuronal cells in the first chamber before establishing connections with the biological tissue in the second chamber. This preliminary action allows neuronal processes to be prepared and directed through the microfluidic channels in advance, making the subsequent integration with tissue simpler and maintaining ease of manufacture while achieving complete physiological functionality.
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
Enables the development of predictive and reproducible in vitro models that mimic human tissue responses, allowing for effective drug screening, toxicity testing, and disease modeling, while reducing the need for animal testing.
Implementation Method 1
a microfluidic layer receivable on the microfluidic layer-receiving portion of the bottom wall of the insert and comprising channels for orienting axonal growth
Implementation Method 2
an upwardly extending feed well comprising a seeding chamber extending longitudinally therethrough and being configured to receive the neuronal cells and additional culture medium fluid therein, the seeding chamber being configured to be in fluid communication with the channels of the microfluidic layer to enable at least a portion of the additional culture medium fluid to flow therein
Data Source
AI summary
There is provided a cell culture device for preparing a compartmentalized in vitro model using neuronal cells. The cell culture device can include an insert insertable in a reservoir of a cell culture plate, a microfluidic layer receivable on or within the insert and an upwardly extending feed well. The microfluidic layer includes channels for orienting axonal growth, and the feed well includes a seeding chamber to receive the neuronal cells therein, the seeding chamber being configured to be in fluid communication with the channels of the microfluidic layer. Alternatively, the cell culture device can include a multi-well insert that includes a plurality of insert wells configured to receive a microfluidic layer therein, the insert wells being in fluid communication with a feed well that is configured to receive the neuronal cells therein. The cell culture device can further include an electrode layer provided in proximity of the microfluidic layer.