TEER measurement techniques for in vitro barrier model systems

TEER measurement techniques for in vitro barrier model systems

2015 April | Balaji Srinivasan, Aditya Reddy Kolli, Mandy Brigitte Esch, Hasan Erbil Abaci, Michael L. Shuler, and James J. Hickman
This paper reviews various TEER measurement techniques for in vitro barrier models, including the blood-brain barrier (BBB), gastrointestinal (GI) tract, and pulmonary models. TEER is a widely accepted method to assess the integrity of tight junctions in cell culture models of endothelial and epithelial monolayers. TEER measurements can be performed in real-time without cell damage and are based on measuring ohmic resistance or impedance across a wide spectrum of frequencies. Commercially available systems and custom-built microfluidic implementations have been used to measure TEER for various cell types. Factors such as temperature, medium formulation, and cell passage number can affect TEER values. The paper discusses the strengths and weaknesses of different TEER measurement techniques, the significance of TEER in drug toxicity studies, and various in vitro models and microfluidic implementations utilizing TEER measurements in some widely studied barrier models. It also examines the factors that can affect TEER measurements. TEER measurement methods include the Ohm's Law method and impedance spectroscopy. The Ohm's Law method involves measuring the electrical resistance of a cellular monolayer using electrodes placed in the apical and basolateral compartments. Impedance spectroscopy, when combined with a fitting algorithm, provides a more accurate representation of TEER values than traditional DC/single frequency AC measurement systems. Impedance spectroscopy measures the amplitude and phase response of the resulting current after applying a small amplitude AC excitation signal with a frequency sweep. Organs-on-chips provide a microengineered biomimetic device containing microfluidic channels and chambers populated by living cells, which replicate key functional units of living organs. These systems offer advantages such as enabling the study of cells under physiologically relevant fluid flow conditions and precise control over physiologic stresses, chemical signaling, and cell-to-cell interaction. The paper discusses the advantages of organs-on-chips for TEER measurement, in vitro models of some widely studied cellular barriers, TEER measurements with in vitro models, and various factors affecting TEER values. The blood-brain barrier (BBB) is an active interface between the circulatory system and the central nervous system, restricting the free movement of different substances between the two compartments. TEER has been the most commonly used parameter to evaluate the functionality of the BBB. Various in vitro models of the BBB have been developed, including co-culture models with other brain cell types and chemical treatments to promote BBB formation. The TEER values measured in vivo have been reported to be as high as 5900 Ω·cm², which is markedly larger than that achieved by the majority of the currently available in vitro models. The gastrointestinal tract models involve the study of drug transport across the intestinal membrane, which is a complex and dynamic process. Caco-2 cells are widely used for developing human GI tract in vitro models. These cells can form a tightly packed monolayer and generate a TEER of 150-This paper reviews various TEER measurement techniques for in vitro barrier models, including the blood-brain barrier (BBB), gastrointestinal (GI) tract, and pulmonary models. TEER is a widely accepted method to assess the integrity of tight junctions in cell culture models of endothelial and epithelial monolayers. TEER measurements can be performed in real-time without cell damage and are based on measuring ohmic resistance or impedance across a wide spectrum of frequencies. Commercially available systems and custom-built microfluidic implementations have been used to measure TEER for various cell types. Factors such as temperature, medium formulation, and cell passage number can affect TEER values. The paper discusses the strengths and weaknesses of different TEER measurement techniques, the significance of TEER in drug toxicity studies, and various in vitro models and microfluidic implementations utilizing TEER measurements in some widely studied barrier models. It also examines the factors that can affect TEER measurements. TEER measurement methods include the Ohm's Law method and impedance spectroscopy. The Ohm's Law method involves measuring the electrical resistance of a cellular monolayer using electrodes placed in the apical and basolateral compartments. Impedance spectroscopy, when combined with a fitting algorithm, provides a more accurate representation of TEER values than traditional DC/single frequency AC measurement systems. Impedance spectroscopy measures the amplitude and phase response of the resulting current after applying a small amplitude AC excitation signal with a frequency sweep. Organs-on-chips provide a microengineered biomimetic device containing microfluidic channels and chambers populated by living cells, which replicate key functional units of living organs. These systems offer advantages such as enabling the study of cells under physiologically relevant fluid flow conditions and precise control over physiologic stresses, chemical signaling, and cell-to-cell interaction. The paper discusses the advantages of organs-on-chips for TEER measurement, in vitro models of some widely studied cellular barriers, TEER measurements with in vitro models, and various factors affecting TEER values. The blood-brain barrier (BBB) is an active interface between the circulatory system and the central nervous system, restricting the free movement of different substances between the two compartments. TEER has been the most commonly used parameter to evaluate the functionality of the BBB. Various in vitro models of the BBB have been developed, including co-culture models with other brain cell types and chemical treatments to promote BBB formation. The TEER values measured in vivo have been reported to be as high as 5900 Ω·cm², which is markedly larger than that achieved by the majority of the currently available in vitro models. The gastrointestinal tract models involve the study of drug transport across the intestinal membrane, which is a complex and dynamic process. Caco-2 cells are widely used for developing human GI tract in vitro models. These cells can form a tightly packed monolayer and generate a TEER of 150-
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