Microfluidic channel sensory system for electro-addressing cell location, determining confluency, and quantifying a general number of cells

Abstract

Microfluidics is a highly useful platform for culturing, monitoring, and testing biological cells. The integration of electrodes into microfluidic channels extends the functionality, sensing, and testing capabilities of microfluidic systems. By employing an electrochemical impedance spectroscopy (EIS) technique, the non-invasive, label-free detection of the activities of cells in real-time can be achieved. To address the movement toward spatially resolving cells in cell culture, we developed a sensory system capable of electro-addressing cell location within a microfluidic channel. This simple system allows for real-time cell location, integrity monitoring (of barrier producing cells), and confluency sensing without the need for frequent optical evaluation—saving time. EIS results demonstrate that cells within microfluidic channels can be located between various pairs of electrodes at different positions along the length of the device. Impedance spectra clearly differentiates between empty, sparse, and confluent microfluidic channels. The system also senses the level of cell confluence between electrode pairs—allowing for the relative quantification of cells in different areas of the microfluidic channel. The system’s electrode layout can easily be incorporated into other devices. Namely, organ-on-a-chip devices, that require the monitoring of precise cell location and confluency levels for understanding tissue function, modeling diseases, and for testing therapeutics.

3D In Vitro Blood‐Brain‐Barrier Model for Investigating Barrier Insults

“…[ 35,38,69 ] Therefore, the sensitivity and the reliability of TEER measurements and the corresponding information on the tightness of the whole barrier may be compromised. [ 35 ] To obtain sensitive TEER measurements, thin‐film TEER sensors have been integrated within microfluidics‐based systems [ 23,36,70,71 ] using different electrode materials (e.g., Au, Ag, Pt) on a variety of substrates (e.g., glass, PET, PC). Although electrodes, realized through metal films of a few tens of micrometer thickness, have been used as partially transparent electrodes for visible light, [ 36 ] it has to be noted that metal films do not enable unhindered optical access for high‐resolution microscopy.…”

P450 oxidoreductase regulates barrier maturation by mediating retinoic acid metabolism in a model of the human BBB

“…iBMECs are increasingly used to model various aspects of the BBB ( Motallebnejad et al., 2022 ; Ohshima et al., 2019 ; Park et al., 2019 ; Piantino et al., 2022 ; Rapier et al., 2022 ; Vatine et al., 2019 ). Their strength lies in their scalability and functional properties and the opportunity to model disorders in a personalized manner ( Lim et al., 2017 ; Vatine et al., 2017 ; Wu et al., 2021 ).…”

Concepts, electrode configuration, characterization, and data analytics of electric and electrochemical microfluidic platforms: a review

“…Rapier et al determined the position and the movements of cells in cell culture by using numerous electrode pairs along the channel length in real-time. 137 The impedance signals revealed the cell confluency levels in the sensing region and evaluated the number of cells inside the device. 137 Regarding cell migration analysis, ECIS techniques allow for conducting labor-saving, non-invasive, continuous, and real-time measurements.…”

“…137 The impedance signals revealed the cell confluency levels in the sensing region and evaluated the number of cells inside the device. 137 Regarding cell migration analysis, ECIS techniques allow for conducting labor-saving, non-invasive, continuous, and real-time measurements. There have been many attempts to conduct wound-healing assays using ECIS techniques to evaluate cell migration.…”