(1044-A) A high throughput TEER measurement device for on-chip tissue barrier assessment

Abstract: Introduction
Trans Epithelial/Endothelial Electrical Resistance (TEER) is a measurement technique that has been widely
adopted to evaluate tissue barrier function in vitro, typically in organ-on-chip (OOC) models. This method is a non-
invasive, label-free alternative to tracer transportation assays which makes it suitable for non-destructive, real-
time assessment of cell response to biochemical stimuli, enabling high throughput drug screening capability of
OOC technology. However, the widely used conventional TEER measurement devices in the market offer single-
channel, fixed-frequency impedance measurement through chopstick-like electrodes. As a result, the handheld
TEER readings provide low reproducibility, and non-uniform current density, and are extremely time-consuming.
We introduce the AKITA® Lid, a high throughput TEER device that performs fast and reliable measurement
coupled with a standardized OOC platform termed AKITA® Plate, which allows the establishment and
measurement of up to 32 barrier cultures on one ANSI/SLAS standard plate. With our platform, a Gut-On-Chip
was developed and assessed using TEER.

Methods
The impedance is measured with the 4-electrodes configuration on a wide frequency range, under 2 minutes for
one AKITA® Plate96. The TEER is calculated by fitting the data with an electrical equivalent model. The data is
displayed in real-time on a web application in which the user can check the measurements and control the device
remotely.
Colon epithelial cells were grown on the AKITA® Plate96, on a semi-permeable membrane separating the open-
top culture chamber from a bottom microfluidic channel. 32 culture units in 96-well plate format were formed and
measured daily with the AKITA® LID.

Results & Discussion
To validate the AKITA Lid functionality, a buffer measurement test with different NaCl concentrations was
performed to compare our device with the EVOM1 (World Precision Instruments). The experiment yielded
comparable results for both devices.
For the Gut-on-Chip, TEER and fluorescent-based permeability assays are performed to quantify the barrier
integrity parallelly. Grown under bilateral continuous flow, the Gut-on-chip grown on AKITA® Plate reaches
permeability coefficients of around 1E-6 cm/s, approaching values detected in vivo. Our TEER values stabilized
around 250 Ohms.cm2, close to what can be commonly found in the literature.

Conclusion
We presented a high throughput TEER device, AKITA® LID, that enables fast and reliable measurements, with a
wide range of frequencies. The device ensures the reproducibility of the measurements thanks to the standardized
and high throughput multiplexed design of the electrode array. The device was validated by multiple approaches
including benchmarking with a commercially available device as well as real measurements on in vitro gut model
formed by the AKITA® Plate96. Our results also suggest that the AKITA® Plate and the AKITA® LID can further
be applied to a wide range of tissue barrier models to accelerate in vitro model development in the context of drug
testing.