TEER measurement techniques for in vitro barrier model systems

Abstract

Transepithelial/transendothelial electrical resistance (TEER) is a widely accepted quantitative technique to measure the integrity of tight junction dynamics in cell culture models of endothelial and epithelial monolayers. TEER values are strong indicators of the integrity of the cellular barriers before they are evaluated for transport of drugs or chemicals. TEER measurements can be performed in real time without cell damage and generally are based on measuring ohmic resistance or measuring impedance across a wide spectrum of frequencies. The measurements for various cell types have been reported with commercially available measurement systems and also with custom-built microfluidic implementations. Some of the barrier models that have been widely characterized using TEER include the blood-brain barrier (BBB), gastrointestinal (GI) tract, and pulmonary models. Variations in these values can arise due to factors such as temperature, medium formulation, and passage number of cells. The aim of this article is to review the different TEER measurement techniques and analyze their strengths and weaknesses, determine the significance of TEER in drug toxicity studies, examine the various in vitro models and microfluidic organs-on-chips implementations using TEER measurements in some widely studied barrier models (BBB, GI tract, and pulmonary), and discuss the various factors that can affect TEER measurements.

Keywords: TEER; drug toxicity; impedance spectroscopy; in vitro barrier models; organs-on-chips.

Figure 1

TEER measurement with chopstick electrodes. The total electrical resistance includes the ohmic resistance of the cell layer R_TEER, the cell culture medium R_M, the semipermeable membrane insert R_I and the electrode medium interface R_EMI.

Figure 2

(a) TEER measurement concept based on impedance spectroscopy (b) Components of Impedance.

Figure 3

(a) A typical equivalent circuit diagram that can be applied to analyze the impedance spectrum of cellular systems. (b) Simplified equivalent circuit (c) A typical impedance spectrum with distinct frequency dependent regions. Adapted from Benson et al.

Figure 4

A schematic of BBB showing various components, brain capillary endothelial cells (BCECs), basement membrane, pericytes and astrocytes. Adapted from Wong et al.

Figure 5

A schematic of the GI tract model showing various components, intestinal epithelial cells (IEC), goblet cell. Adapted from Antonissen et al..

Figure 6

A schematic overview of the human lung. Cells of the airway epithelium comprises ciliated, undifferentiated columnar, clara and basal cells. Cells of the alveolar epithelium comprise AT-I and AT-II type cells. Adapted from Hollenhorst, 2011.