Organ-on-a-Chip Platform with an Integrated Screen-Printed Electrode Array for Real-Time Monitoring Trans-Epithelial Barrier and Bubble Formation

Abstract

Cellular tight junctions play a key role in establishing a barrier between different compartments of the body by regulating the selective passage of different solutes across epithelial and endothelial tissues. Over the past decade, significant efforts have been conducted to develop more clinically relevant “organ-on-a-chip” models with integrated trans-epithelial electrical resistance (TEER) monitoring systems to help better understand the fundamental underpinnings of epithelial tissue physiology upon exposure to different substances. However, most of these platforms require the use of high-cost and time-consuming photolithography processes, which limits their scalability and practical implementation in clinical research. To address this need, we have developed a low-cost microfluidic platform with an integrated electrode array that allows continuous real-time monitoring of TEER and the risk of bubble formation in the microfluidic system by using scalable manufacturing technologies such as screen printing and laser processing. The integrated printed electrode array exhibited excellent stability (with less than ∼0.02 Ω change in resistance) even after long-term exposure to a complex culture medium. As a proof of concept, the fully integrated platform was tested with HMT3522 S1 epithelial cells to evaluate the tight barrier junction formation through TEER measurement and validated with standard immunostaining procedures for Zonula occludens-1 protein. This platform could be regarded as a stepping stone for the fabrication of disposable and low-cost organ and tissue-on-a-chip models with integrated sensors to facilitate studying the dynamic response of epithelial tissues to different substances in more physiologically relevant conditions.

Laser-assisted surface alloying of titanium with silver to enhance antibacterial and bone-cell mineralization properties of orthopedic implants

“…The field emission scanning electron microscope (FE-SEM) (Hitachi-S4800) with built-in energy-dispersive X-ray spectroscopy (EDX) was used to understand the morphology of Ti samples before and after the LSA process on Ag-coated samples. 32 Additionally, the cross-sectional imaging of the developed surface was analyzed using Focused Ion Beam (FIB) milling (Helios 5 DualBeam, Thermofisher Scientific) and EDX analysis at the interface. The elemental composition of Ti samples before and after LSA process was determined by EDX and grazing angle X-ray diffraction (GIXRD, PANalytical Empyrean Diffractometer system with a Cu Kα1, λ = 1.5406 Å source) analysis.…”

Integrated Electrochemical and Optical Biosensing in Organs‐on‐Chip

“…[39] An electrode array integrated in an OoC platform for continuous TEER monitoring was fabricated using screen printing and laser processing. [40] The electrodes showed substantial stability with change in resistance of less than 0.02 Ω. An interesting opportunity lies in the integration of TEER sensing electrodes on flexible substrates, specifically for stretching tissues, as demonstrated in lung-on-chip devices.…”

“…Other applications include heart (Figure 2A) [37] and epidermis, [38] and real‐time measurement of electric activity of cells during proliferation [39] . An electrode array integrated in an OoC platform for continuous TEER monitoring was fabricated using screen printing and laser processing [40] . The electrodes showed substantial stability with change in resistance of less than 0.02 Ω.…”

Advances in sensor developments for cell culture monitoring

“…As an alternative, a less invasive approach is suggested to use electrical measurements to evaluate the barrier function of epithelial cells on a porous cell culture-supported substrate. The electrical cell-substrate impedance sensing technique is one example of the cell-to-cell electrical signaling method [21,48,49] that indirectly interprets the cell status in microscale chip format.…”