Somatic Cell Electrical Biosensor for Small-Volume TEER Sensing
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Solution Overview
Problem
Existing TEER apparatus face challenges in immobilizing cells on electrodes due to antimicrobial properties of silver electrodes, requiring large sample sizes and invasive testing procedures, which are problematic for valuable or limited samples like biopsies.
Innovation Solution
A biosensor with a biologically inert working electrode and a reference electrode, where somatic cells are immobilized, allowing for direct detection of transepithelial/transendothelial electrical resistance without a cell monolayer, enabling accurate measurements with small sample volumes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If silver electrodes are used in TEER apparatus, then electrical resistance measurement capability is achieved, but cell immobilization fails due to antimicrobial properties
Solution Approach 1:
A porous membrane serves as an intermediary between the silver electrode and the cells. The membrane allows electrical measurements to be conducted while providing a suitable surface for cell attachment and growth, effectively mediating between the electrical measurement requirement and the cell biology requirement
Solution Approach 2:
The patent employs disposable porous membranes that are discarded after use, eliminating the need for complex cleaning and sterilization procedures between measurements. This allows for reliable cell immobilization on each new membrane without cross-contamination or degradation of the electrode surface
2Reliability
If cells are grown in vitro in a well to form a monolayer, then cell culture is achieved, but large sample volumes are required
Solution Approach 1:
The patent transitions from growing cells in a three-dimensional well environment to forming monolayers on two-dimensional porous membranes. This dimensional change reduces the volume of culture medium and sample required while maintaining cell viability and function
Solution Approach 2:
Porous membranes provide a high surface area to volume ratio structure that supports cell monolayer formation with minimal sample volume. The porous structure allows cells to attach and form confluent layers while requiring significantly less culture medium compared to traditional well-based systems
3Measurement precision
If four electrodes are used for TEER measurement, then resistance sensing capability is achieved, but device complexity increases
Solution Approach 1:
The patent combines the reference electrode function with the porous membrane structure itself, eliminating the need for separate reference electrodes. This merging of functions reduces the total electrode count from four to two while maintaining measurement capability
Solution Approach 2:
The porous membrane serves multiple functions simultaneously: it acts as a support structure for cell growth, provides a barrier between electrodes, enables electrical measurements, and eliminates the need for separate reference electrodes. This multi-functionality simplifies the overall device architecture
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 biosensor provides high selectivity and accuracy in detecting target compositions using small sample volumes, such as 1 μL to 500 μL, by measuring changes in electrical resistance of immobilized somatic cells.
Implementation Method 1
detecting a first resistance measurement and a second resistance measurement, where the somatic cells are immobilized on the working electrode during both the first resistance measurement and the second resistance measurement
Data Source
AI summary
A biosensor having somatic cells immobilized on an electrode formed from a biologically inert material for sensing transepithelial/transendothelial electrical resistance is provided. The biosensor includes a working electrode formed from gold, graphene, carbon nanotube, or alloys or combinations thereof, having somatic cells formed directly thereon. With such a configuration, a very small sample size may be used while still eliciting an electrical response in the presence of a target composition.