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Article

Double-Layered Microphysiological System Made of Polyethylene Terephthalate with Trans-Epithelial Electrical Resistance Measurement Function for Uniform Detection Sensitivity

1
Micro/Nano Technology Center, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan
2
Department of Medicine, Division of Pulmonary Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan
3
The Institute of Medical Sciences, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan
4
SCREEN Holdings Co., Ltd., Kyoto, Kyoto 612-8486, Japan
5
TOKYO OHKA KOGYO Co., Ltd., Koza, Kanagawa 253-0114, Japan
*
Author to whom correspondence should be addressed.
Biosensors 2025, 15(10), 663; https://doi.org/10.3390/bios15100663
Submission received: 20 August 2025 / Revised: 25 September 2025 / Accepted: 28 September 2025 / Published: 2 October 2025

Abstract

Microphysiological systems (MPSs) have emerged as alternatives to animal testing in drug development, following the FDA Modernization Act 2.0. Double-layer channel-type MPS chips with porous membranes are widely used for modeling various organs, including the intestines, blood–brain barrier, renal tubules, and lungs. However, these chips faced challenges owing to optical interference caused by light scattering from the porous membrane, which hinders cell observation. Trans-epithelial electrical resistance (TEER) measurement offers a non-invasive method for assessing barrier integrity in these chips. However, existing electrode-integrated MPS chips for TEER measurement have non-uniform current densities, leading to compromised measurement accuracy. Additionally, chips made from polydimethylsiloxane have been associated with drug absorption issues. This study developed an electrode-integrated MPS chip for TEER measurement with a uniform current distribution and minimal drug absorption. Through a finite element method simulation, electrode patterns were optimized and incorporated into a polyethylene terephthalate (PET)-based chip. The device was fabricated by laminating PET films, porous membranes, and patterned gold electrodes. The chip’s performance was evaluated using a perfused Caco-2 intestinal model. TEER levels increased and peaked on day 5 when cells formed a monolayer, and then they decreased with the development of villi-like structures. Concurrently, capacitance increased, indicating microvilli formation. Exposure to staurosporine resulted in a dose-dependent reduction in TEER, which was validated by immunostaining, indicating a disruption of the tight junction. This study presents a TEER measurement MPS platform with a uniform current density and reduced drug absorption, thereby enhancing TEER measurement reliability. This system effectively monitors barrier integrity and drug responses, demonstrating its potential for non-animal drug-testing applications.
Keywords: microphysiological system (MPS); trans-epithelial electro resistance (TEER); microfluidic device; gut-on-a-chip; Intestinal epithelial model; polyethylene terephthalate (PET) microphysiological system (MPS); trans-epithelial electro resistance (TEER); microfluidic device; gut-on-a-chip; Intestinal epithelial model; polyethylene terephthalate (PET)

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MDPI and ACS Style

Kutsuzawa, N.; Nakamura, H.; Chen, L.; Fujioka, R.; Mori, S.; Nakatani, N.; Yoshioka, T.; Kimura, H. Double-Layered Microphysiological System Made of Polyethylene Terephthalate with Trans-Epithelial Electrical Resistance Measurement Function for Uniform Detection Sensitivity. Biosensors 2025, 15, 663. https://doi.org/10.3390/bios15100663

AMA Style

Kutsuzawa N, Nakamura H, Chen L, Fujioka R, Mori S, Nakatani N, Yoshioka T, Kimura H. Double-Layered Microphysiological System Made of Polyethylene Terephthalate with Trans-Epithelial Electrical Resistance Measurement Function for Uniform Detection Sensitivity. Biosensors. 2025; 15(10):663. https://doi.org/10.3390/bios15100663

Chicago/Turabian Style

Kutsuzawa, Naokata, Hiroko Nakamura, Laner Chen, Ryota Fujioka, Shuntaro Mori, Noriyuki Nakatani, Takahiro Yoshioka, and Hiroshi Kimura. 2025. "Double-Layered Microphysiological System Made of Polyethylene Terephthalate with Trans-Epithelial Electrical Resistance Measurement Function for Uniform Detection Sensitivity" Biosensors 15, no. 10: 663. https://doi.org/10.3390/bios15100663

APA Style

Kutsuzawa, N., Nakamura, H., Chen, L., Fujioka, R., Mori, S., Nakatani, N., Yoshioka, T., & Kimura, H. (2025). Double-Layered Microphysiological System Made of Polyethylene Terephthalate with Trans-Epithelial Electrical Resistance Measurement Function for Uniform Detection Sensitivity. Biosensors, 15(10), 663. https://doi.org/10.3390/bios15100663

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