Microfluidic Device with Integrated Membrane Electrodes for TEER Measurement

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Solution Overview

Problem

Current methods fail to accurately measure transepithelial electrical resistance (TEER) and impedance of cell layers on porous membranes, as electrodes cannot be positioned close enough to simulate an in vivo-like situation effectively.

Innovation Solution

A microfluidic device with electrodes integrated onto porous and flexible membranes allows for precise measurement of TEER and impedance by positioning electrodes directly on the membrane surface, enabling direct contact with cell layers and eliminating the influence of the porous membrane, thus enabling accurate TEER and impedance measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If electrodes are positioned close to cells on a porous membrane, then measurement precision of TEER and impedance is improved, but conventional methods cannot achieve this positioning

Engineering Contradiction:
ImproveTEER and impedance measurement precisionVSAvoidelectrode positioning capability
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the electrode structure with the porous membrane by integrating electrodes directly into the membrane matrix. This combination allows electrodes to be positioned in direct contact with cell layers on the membrane surface, achieving precise TEER and impedance measurements while simplifying the overall device structure by eliminating separate electrode positioning mechanisms.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The porous membrane serves as an intermediary substrate that supports both the electrode structure and the cell layer. By positioning electrodes on this intermediate membrane surface, the patent enables direct electrical contact with cells while maintaining the physiological relevance of the porous membrane structure, thus achieving accurate measurements without complex positioning systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If cells are grown on a porous membrane to simulate in vivo conditions, then biological realism is improved, but electrode positioning close to cells becomes impossible

Engineering Contradiction:
Improvein vivo-like simulation accuracyVSAvoidTEER and impedance measurement accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent combines the porous membrane structure with integrated electrodes, creating a unified platform that simultaneously provides in vivo-like conditions for cell growth and enables direct electrical measurements. The electrodes are embedded within the porous membrane matrix, allowing them to contact cell layers while the membrane maintains its physiological relevance.

Inventive Principle:
Principle #5Merging (Combining)

3Productivity

If multiple cell barriers are tested simultaneously, then productivity is improved, but device complexity increases

Engineering Contradiction:
Improvenumber of cell barriers tested per deviceVSAvoidmicrochannel and compartment structure
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent divides the device into multiple independent microchannels, each containing separate compartments that can host different cell barriers. This segmentation allows simultaneous testing of multiple cell barriers in parallel, improving productivity while maintaining manageable device complexity through modular channel design.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microchannel structure with integrated electrodes serves multiple functions: it provides separate testing environments for multiple cell barriers, enables electrical measurements through integrated electrodes, and maintains fluid flow control. This multi-functionality allows the device to test multiple cell barriers simultaneously without proportionally increasing complexity.

Inventive Principle:
Principle #6Universality (Multi-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

This approach allows for more precise and direct measurement of TEER and impedance of cell layers, enabling the assessment of cell barrier integrity and surface coverage, overcoming the limitations of conventional methods by allowing multiple cell barriers to be tested within a single device.

Implementation Method 1

The measurement of electrical resistance and impedance requires the presence of electrodes close to the cells and cell layer

Methodology Applied
Scientific EffectElectrical resistance measurement: Electrical Resistance

Implementation Method 2

determining the impedance of cells, a cell layer or a cell assembly

Methodology Applied
Scientific EffectImpedance measurement: Electrical Impedance Tomography

Data Source

PatentEP3722807B1Microfluidic device for measuring cell impedance and transepithelial electrical resistance
Publication Date: 2023.02.15 VIENNA UNIVERSITY OF TECHNOLOGY
  • EP3722807B1 patent drawingFigure 1A
  • EP3722807B1 patent drawingFigure 1B
  • EP3722807B1 patent drawingFigure 1C

AI summary

The present invention relates to a microfluidic device for determining the transepithelial electrical resistance (TEER) of a cell layer or a cell assembly and/or for determining the impedance of cells, a cell layer or a cell assembly, said device comprising at least one microchannel (1) comprising at least a lower and an upper compartment (3, 2) separated by at least one porous membrane (4) and optionally an inner compartment (12), the lower compartment (3) comprising a bottom wall (7) and side walls (8), the upper compartment (2) comprising an upper wall (6) and side walls (8), the bottom and upper wall, the side walls and the at least one porous membrane defining compartment volumes, wherein at least one porous membrane (4) comprises on its surface at least one electrode (5).