Epidermal Sample Holder for Transepithelial Electric Resistance Measurement
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Solution Overview
Problem
Current methods for studying full thickness epidermal samples ex vivo are complex, expensive, and fail to accurately replicate the in vivo skin barrier function, particularly in measuring transepithelial electric resistance and paracellular flux, and are not suitable for intact skin samples.
Innovation Solution
A system comprising two wells with a sample holder that allows for precise measurement of epidermal barrier integrity using transepithelial electric resistance and paracellular flux assays, replacing the conventional Snapwell™ filter with a sandwich system of Plexiglas inserts and a filter paper to hold the epidermal sample, enabling the study of fully stratified epidermal samples from various vertebrates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a Ussing chamber system is used to measure transepithelial electric resistance and paracellular flux, then measurement capability is achieved, but device complexity and cost increase significantly
Solution Approach 1:
The patent creates a simplified copy of the Ussing chamber functionality using a Transwell insert system with standard well plates. This copying approach replicates the essential measurement capability while using commercially available, simpler components that do not require specialized equipment or extensive training to operate
Solution Approach 2:
The invention employs disposable Transwell inserts and standard laboratory well plates instead of expensive, reusable Ussing chamber systems. This approach sacrifices some long-term durability but dramatically reduces initial equipment cost and maintenance requirements, making the measurement capability accessible to more laboratories
2Measurement precision
If a Ussing chamber system is used to measure transepithelial electric resistance and paracellular flux, then measurement capability is achieved, but operational cost increases
Solution Approach 1:
The Transwell insert system serves multiple functions: it can measure both transepithelial electric resistance and paracellular flux, accommodate various cell types and tissue models, and integrate with standard laboratory equipment. This multi-functionality eliminates the need for specialized Ussing chamber equipment, reducing operational costs while maintaining measurement capabilities
Solution Approach 2:
The system allows researchers to perform measurements using standard laboratory equipment and techniques that are already available in most labs. The methodology is self-explanatory and does not require specialized training or support, reducing operational costs associated with technical expertise and equipment maintenance
3Ease of operation
If keratinocyte monolayer models are used to study epidermis, then experimental simplicity is achieved, but biological fidelity deteriorates
Solution Approach 1:
The patent nests keratinocyte monolayers within a three-dimensional extracellular matrix environment that mimics the native epidermal architecture. This nested structure allows cells to be cultured in a biologically relevant context while maintaining the experimental simplicity of cell culture models, thereby improving biological fidelity without sacrificing ease of operation
Solution Approach 2:
The system uses composite structures combining keratinocytes with extracellular matrix components and potentially other cell types to create a more faithful representation of epidermal tissue. This composite approach maintains experimental tractability while capturing the complexity of native epidermal barrier function
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 precise and cost-effective measurement of epidermal barrier integrity and recovery, allowing for the evaluation of various compounds' effects on skin samples, including drug delivery and gene expression, in both healthy and diseased states, and is adaptable for different vertebrate species and skin conditions.
Implementation Method 1
Trans-epithelial electric resistance (TEER) measures the resistance to ion flow
Implementation Method 2
The paracellular flux of macromolecules that typically uses fluorochrome-conjugated probes of different radii to evaluate TJ pore size
Data Source
AI summary
An epidermal sample is placed into a sample holder formed as a sandwich assembly. The sample holder is placed in an upper well within a lower well to be exposed to media in both wells. Properties of the sample can be studied, such as paracellular flux, transepidermal electric resistance, reaction to compounds, and epidermal barrier recovery.