Multi-well plate insert with flat electrodes for impedance measurement
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing multi-well plate systems for measuring cellular and trans-cellular impedance are prone to electrode damage, inconsistent electrode positioning, and liquid level variations, leading to inaccurate and invasive measurements of biological barrier integrity.
Innovation Solution
A multi-well plate system with electrodes integrated into the well insert, arranged flat along the surface to prevent bending and ensure consistent positioning, and a four-terminal measurement system for precise impedance analysis, minimizing the risk of damage and ensuring reproducibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If electrodes are arranged to project into the liquid in the well insert, then electrical contact with the conductive medium is ensured, but the electrodes are susceptible to damage and may contact or damage the cell layer
Solution Approach 1:
The electrodes are arranged flat along the surface of the well insert rather than projecting vertically into the liquid. This dimensional change from vertical projection to horizontal surface arrangement ensures electrical contact with the conductive medium while eliminating the risk of electrodes contacting or damaging the cell layer grown on the membrane.
2Reliability
If electrodes are arranged to project into the liquid in the well insert, then electrical contact is achieved, but the electrodes can be bent or broken easily
Solution Approach 1:
The electrodes are configured as flat surfaces arranged along the well insert surface rather than protruding elements. This dimensional reconfiguration eliminates the mechanical vulnerability of protruding electrodes to bending or breaking while maintaining effective electrical contact with the conductive medium through the liquid medium.
3Adaptability or versatility
If electrodes are positioned in different components of the device, then assembly flexibility is provided, but inconsistent positioning and measurement variability occur
Solution Approach 1:
The electrodes are integrated into the well insert as a single unified component rather than being distributed across separate components. This merging ensures consistent and reproducible electrode positioning for all measurements while maintaining assembly flexibility, as the integrated electrodes move with the well insert as one unit.
4Ease of operation
If simple microscopic observation is used to determine cell layer integrity, then the method is simple and redundant control is provided, but accuracy and sensitivity are insufficient
Solution Approach 1:
The patent introduces an electrical impedance measurement system as an intermediary method between simple microscopic observation and complex electrochemical methods. This intermediary approach uses electrical properties to accurately and sensitively assess cell layer integrity and barrier function, providing quantitative data that bridges the gap between visual inspection and sophisticated electrochemical analysis.
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 accurate, non-invasive, and reproducible measurements of biological barrier integrity by ensuring electrodes are always submerged in the liquid and maintaining consistent positioning, reducing the risk of damage and variability in results.
Implementation Method 1
The electrical resistance, and more generally the impedance across a cell monolayer or multiple layers of cells is a measure of its ion permeability and thus a very useful parameter to determine properties of the biological barrier
Implementation Method 2
Impedance spectroscopy, using a number of defined frequencies, has proved particularly powerful for this purpose. Different from other electrochemical methods, which only work with direct current (DC) voltage or alternating current (AC) voltage with constant frequency, impedance spectroscopy uses AC voltage with sinusoidal, square or triangular waveform frequency, which varies during the measurement
Data Source
Figure 1a~1b
Figure 2a~2c
Figure 3a~3b
AI summary
The invention concerns a well insert (1) for a multi-well plate (2) and a multi-well plate system for use in cell culture. The well insert comprises a planar support (14) having at least one permeable or semi-permeable portion (11), at least one pair of electrodes having a first electrode (41) and a second electrode (42) arranged to measure electrical impedance across a layered cell culture supported by the planar support (14), an insert wall with a projecting portion (13), said projecting portion being configured to interface with the multi-well plate (2) such as to suspend the insert (1) in a well (20), wherein the insert wall (12) together with the planar support (14) separate a first chamber (8) from a second chamber (9), the electrodes (41, 42) being arranged along the inner surface (15) of the insert and the counter-electrode (41, 42) being arranged along the outer surface (16) of the insert. The projecting portion (13) comprises the contact ends (53, 54) of the one or more electrode and of the one or more counter-electrode, such that each electrode connects to a contact point (45) on the multi-well plate 2 and each counter-electrode connects to a contact point (35) on the lid (3), which is positioned on the plate (2) when the system is assembled.