Fabrication and Validation of an Organ-on-chip System with Integrated Electrodes to Directly Quantify Transendothelial Electrical Resistance
September 26th, 2017
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This publication describes the fabrication of an organ-on-chip device with integrated electrodes for direct quantification of transendothelial electrical resistance (TEER). For validation, the blood-brain barrier was mimicked inside this microfluidic device and its barrier function was monitored. The presented methods for electrode integration and direct TEER quantification are generally applicable.
Overview
This publication presents a method for fabricating an organ-on-chip device with integrated electrodes for the direct measurement of transendothelial electrical resistance (TEER). The blood-brain barrier is mimicked within this microfluidic device, allowing for the monitoring of its barrier function.
Key Study Components
Area of Science
- Neuroscience
- Microfluidics
- Biomedical Engineering
Background
- Transendothelial electrical resistance (TEER) is a key measure of barrier function in endothelial cells.
- Organs-on-chips are innovative tools for studying human physiology and disease.
- Integrating electrodes into microfluidic devices enhances measurement capabilities.
- The blood-brain barrier is critical for protecting the brain and is a focus in drug discovery.
Purpose of Study
- To develop a microfluidic chip that allows for direct TEER measurements.
- To validate the device using a model of the blood-brain barrier.
- To provide a method applicable to various organ-on-chip systems.
Methods Used
- Fabrication of PDMS-based microfluidic chips with integrated electrodes.
- Preparation of a porous membrane to mimic the blood-brain barrier.
- Direct measurement of TEER using impedance spectroscopy.
- Cell culture techniques to prepare endothelial cells for the chip.
Main Results
- The fabricated organ-on-chip device successfully integrated electrodes for TEER measurement.
- TEER values were obtained that reflect the barrier function of the blood-brain barrier model.
- The method allows for comparison across different organ-on-chip systems.
- Results indicate potential applications in drug discovery and personalized medicine.
Conclusions
- The integration of electrodes into organ-on-chip devices enhances measurement accuracy.
- This technique can be applied to study various organ systems beyond the blood-brain barrier.
- Future research can leverage this method for insights into health and disease.
Frequently Asked Questions
What is TEER?
TEER stands for transendothelial electrical resistance, a measure of the integrity of endothelial cell layers.
How does the organ-on-chip device work?
The device mimics organ functions and allows for real-time measurement of barrier properties using integrated electrodes.
What are the applications of this technology?
It can be used in drug discovery, studying disease mechanisms, and personalized medicine approaches.
What materials are used in the chip fabrication?
The primary material used is PDMS (polydimethylsiloxane), which is suitable for microfluidic applications.
Can this method be applied to other organ systems?
Yes, the technique can be adapted for use with other organ-on-chip models such as Lung-on-Chip and Gut-on-Chip.
Executive Industry Relevance
Direct quantification of transendothelial electrical resistance (TEER) within organ-on-chip systems addresses a critical need for robust, quantitative assessment of barrier integrity in disease-relevant models. This capability enhances predictive confidence in early-stage drug discovery and supports mechanistic de-risking for blood-brain barrier and other tissue models. The approach enables standardized, reproducible measurements that facilitate cross-platform comparison and portfolio triage.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables direct interrogation of barrier function in human-relevant microphysiological systems.
- Supports mechanistic de-risking by quantifying tight junction integrity in endothelial models.
- Facilitates functional target validation for barrier-modulating compounds.
- Provides quantitative endpoints for hypothesis-driven pathway studies.
Screening & Assay Development
- Delivers standardized TEER readouts for assay reproducibility and benchmarking.
- Prepares validated organ-on-chip platforms for compound screening workflows.
- Enables scalable, multiplexed resistance measurements across multiple devices.
- Supports reliable evaluation of permeability-modifying agents.
Translational & Preclinical Research
- Aligns in vitro barrier models with disease-relevant endpoints for translational continuity.
- Enables monitoring of patient-derived or iPSC-derived endothelial function for personalized research.
- Supports risk-adjusted advancement of candidates targeting CNS or epithelial barriers.
- Provides mechanistic insight into disease models such as neurodegeneration or inflammation.
Pipeline & Workflow Integration
This TEER-enabled organ-on-chip system integrates into the discovery continuum from early target validation through preclinical model development, supporting both mechanistic studies and screening campaigns.
- Discovery Biology: Quantitative TEER measurements clarify barrier function and support hypothesis testing in microfluidic models.
- Screening: Standardized impedance-based readouts enable reproducible, cross-device assay development.
- Analytics: Multipath resistance data provide robust statistical outputs for condition comparison.
- Translational Research: Disease-relevant barrier models facilitate biomarker alignment and preclinical validation.
- Enterprise Reuse: The platform is adaptable to various organ systems, supporting broad R&D utility.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in barrier function studies.
- Operational Value: Streamlines standardization, reproducibility, and scalability of TEER assays.
- Strategic Value: Improves go/no-go decision-making and capital efficiency by providing quantitative, comparable endpoints.
- Portfolio Impact: Enables risk-adjusted prioritization of candidates targeting barrier integrity.
Implementation Considerations
- Requires expertise in microfluidics, impedance spectroscopy, and cell culture.
- Needs access to microfabrication tools and impedance measurement instrumentation.
- Demands cross-team standardization for electrode integration and data analysis.
- Adaptable to various organ-on-chip models with appropriate membrane and cell type selection.
- Practical limitations include electrode placement precision and potential for channel clogging.
Biopharma FAQs
Why does null hypothesis testing matter for TEER quantification?
Null hypothesis testing in TEER measurements enables objective assessment of barrier integrity changes, supporting rigorous target validation and reducing false positives in early discovery. Quantitative resistance data allow teams to distinguish true biological effects from background variability. This statistical rigor underpins confident advancement decisions in barrier-focused programs.
How does independent variable isolation fit TEER measurement workflows?
Isolating variables such as cell type, membrane properties, and channel conditions ensures that TEER changes reflect specific biological interventions. This isolation is critical for mechanistic de-risking and for attributing observed effects to candidate compounds or genetic modifications. It strengthens the predictive value of organ-on-chip barrier models in the discovery pipeline.
What do quantitative impedance spectra enable in organ-on-chip assays?
Quantitative impedance spectra provide direct, reproducible measurements of transendothelial resistance, enabling comparison across devices and experimental conditions. These outputs support benchmarking, assay optimization, and robust statistical analysis for screening and validation. They are essential for establishing assay reliability and translational relevance.
Why are replication requirements critical for TEER-based collaboration?
Replication of TEER measurements across chips and experiments ensures data reliability and facilitates cross-functional collaboration between discovery, screening, and translational teams. Consistent protocols and standardized outputs enable meaningful data sharing and portfolio-wide benchmarking. This reproducibility is vital for enterprise-scale decision-making.
Which statistical analysis capabilities are needed before TEER implementation?
Robust statistical analysis of impedance and TEER data requires tools for multi-path resistance calculation, variance assessment, and threshold determination. Teams must validate measurement consistency and distinguish signal from noise before integrating TEER endpoints into screening or translational workflows. These capabilities underpin confident, data-driven R&D progression.
