Integrated TEER-MEA Organ-on-Chip for Simultaneous Cell Monitoring
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Solution Overview
Problem
Current micro-engineered cell culture models, such as Organs-on-Chips, lack integration of transendothelial/transepithelial electric resistance (TEER) and multi-electrode array (MEA) sensing elements in a single system, limiting their ability to simultaneously monitor electrical activity and barrier function of endothelial and cardiac cells.
Innovation Solution
A microfluidic Organ-on-Chip device with a membrane layer separating top and bottom microchannels, featuring TEER measurement electrodes on both surfaces for direct monitoring of cell function and electrical activity, and a multi-electrode array layer for assessing electrical activity of cells, enabling real-time assessment of endothelial and cardiac functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If TEER electrodes are integrated close to the cellular monolayer, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent combines TEER measurement electrodes and MEA electrodes into a single integrated device structure, where both electrode types are incorporated on the same chip substrate. This merging allows simultaneous measurement of both TEER and electrical activity without requiring separate devices, thereby improving measurement precision while managing device complexity through unified design.
Solution Approach 2:
The device is designed to perform multiple functions: TEER measurement, electrical activity recording, and barrier integrity assessment, all within a single platform. The multi-functional design allows the same device structure to support both TEER electrodes and MEA electrodes, reducing overall system complexity while maintaining high measurement precision for both functions.
2Adaptability or versatility
If multiple sensing elements are integrated to assess multiple cellular functions, then measurement capability is improved, but device complexity increases
Solution Approach 1:
The patent merges TEER sensing elements and MEA sensing elements into a single integrated device, enabling simultaneous assessment of barrier function and electrical activity. This combination allows the device to monitor multiple cellular functions (endothelial barrier integrity and cardiac/neuronal electrical activity) without requiring separate experimental setups.
Solution Approach 2:
The device is designed as a universal platform that can assess multiple cellular functions including barrier integrity, electrical activity, and potentially other physiological parameters. The multi-functional design enables the same device to study different cell types (endothelial cells, cardiac cells, neuronal cells) and different physiological processes within a single experimental system.
3Ease of manufacture
If commercial MEA with fixed electrode configuration is used, then ease of manufacture is improved, but adaptability to microchannel designs decreases
Solution Approach 1:
The patent segments the electrode array into modular units that can be configured to match different microchannel geometries. Rather than using a fixed commercial MEA configuration, the electrode layout is divided into sections that can be adapted to various microchannel designs, maintaining ease of manufacture through standardized fabrication processes while improving adaptability.
Solution Approach 2:
The patent transitions from fixed two-dimensional commercial MEA configurations to customizable electrode arrangements that can be optimized for three-dimensional microchannel structures. This dimensional adaptation allows electrodes to be positioned and oriented to match complex microchannel geometries, improving versatility while maintaining manufacturing feasibility through planar fabrication techniques.
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 integrated TEER-MEA system allows for simultaneous and accurate monitoring of endothelial barrier function and cardiac electrical activity, enhancing the capability to study vascular diseases and drug responses, as demonstrated by sensitivity to inflammatory stimuli and cardiac effects.
Implementation Method 1
The direct measurement of electrical resistance over a tissue barrier, also referred to as transendothelial/transepithelial electric resistance (TEER), is a fast, label-free, and highly sensitive measurement of the barrier integrity and permeability.
Implementation Method 2
Extracellular measurements of electric cell activity in the form of multi-electrodes arrays (MEAs) is an invaluable tool for assessment of neural and muscle cell function.
Data Source
AI summary
An organ-on-chip device for monitoring a biological function and including a membrane layer located at an interface region between a top microchannel and the a microchannel. The membrane includes a first type of cells forming a barrier between the top microchannel and the bottom microchannel. The device further includes a top layer having a first plurality of transendothelial electrical resistance (TEER) measurement electrodes for enabling direct monitoring of cell function and electrical activity of the first type of cells on the membrane. The device also has a multi-electrode array (MEA) layer with a second plurality of TEER measurement electrodes for enabling direct monitoring of cell function and electrical activity of a second type of cells on the MEA layer.