Organs-on-Chips with combined multi-electrode array and transepithelial electrical resistance measurement...

Area of Science:

• Biomedical Engineering
• Microfluidics
• Cellular Biology

Background:

• Organs-on-a-Chips (OoCs) offer advanced in vitro models.
• Integrating real-time sensing capabilities into OoCs is crucial for comprehensive analysis.
• Current OoC platforms often lack multifunctional sensing for simultaneous physiological parameter assessment.

Purpose of the Study:

• To fabricate microfluidic cell culture devices (Organs-on-a-Chips) with integrated multi-electrode arrays (MEAs) and transepithelial electrical resistance (TEER) sensing.
• To demonstrate the capability of these enhanced chips for simultaneous real-time measurement of cellular electrical activity and tissue barrier function.
• To validate the utility of the TEER-MEA chip in assessing dynamic biological responses to stimuli and therapeutics.

Main Methods:

• Fabrication of a dual-channel, endothelialized heart-on-a-chip device incorporating MEA and TEER electrodes.
• Culture of human cardiomyocytes and a primary human endothelial cell monolayer within the chip.
• Simultaneous measurement of cellular electrical activity (via MEA) and tissue barrier function (via TEER).
• Challenging the chip with tumor necrosis factor alpha (TNF-α) and isoproterenol to assess responses.

Main Results:

• Successful integration of MEA and TEER sensing capabilities into the Organ-on-a-Chip device during fabrication.
• Demonstrated simultaneous real-time monitoring of cardiac electrical activity and endothelial barrier function.
• Observed dynamic alterations in vascular permeability and cardiac function in response to TNF-α and isoproterenol.
• Confirmed the TEER-MEA chip's ability to detect functional changes in response to inflammatory stimuli and drugs.

Conclusions:

• The developed Organ Chip with integrated TEER-MEA sensing provides a powerful tool for real-time, multifunctional biological assessment.
• This technology enables simultaneous evaluation of tissue barrier integrity and cellular electrophysiology within a single microfluidic device.
• The TEER-MEA Organ Chip holds significant potential for drug screening, toxicity testing, and advancing personalized medicine through accurate in vitro modeling.