Direct quantification of transendothelial electrical resistance in organs-on-chips

Marieke Willemijn van der Helm, Mathieu Odijk, Jean-Philippe Frimat, Andries Dirk van der Meer, Jan C.T. Eijkel, Albert van den Berg, Loes Irene Segerink

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Abstract

Measuring transendothelial or transepithelial electrical resistance (TEER) is a widely used method to monitor cellular barrier tightness in organs-on-chips. Unfortunately, integrated electrodes close to the cellular barrier hamper visual inspection of the cells or require specialized cleanroom processes to fabricate see-through electrodes. Out-of-view electrodes inserted into the chip's outlets are influenced by the fluid-filled microchannels with relatively high resistance. In this case, small changes in temperature or medium composition strongly affect the apparent TEER. To solve this, we propose a simple and universally applicable method to directly determine the TEER in microfluidic organs-on-chips without the need for integrated electrodes close to the cellular barrier. Using four electrodes inserted into two channels – two on each side of the porous membrane – and six different measurement configurations we can directly derive the isolated TEER independent of channel properties. We show that this method removes large variation of non-biological origin in chips filled with culture medium. Furthermore, we demonstrate the use of our method by quantifying the TEER of a monolayer of human hCMEC/D3 cerebral endothelial cells, mimicking the blood-brain barrier inside our microfluidic organ-on-chip device. We found stable TEER values of 22 Ω cm2±1.3 Ω cm2 (average ± standard error of the mean of 4 chips), comparable to other TEER values reported for hCMEC/D3 cells in well-established Transwell systems. In conclusion, we demonstrate a simple and robust way to directly determine TEER that is applicable to any organ-on-chip device with two channels separated by a membrane. This enables stable and easily applicable TEER measurements without the need for specialized cleanroom processes and with visibility on the measured cell layer
Original languageEnglish
Pages (from-to)924-929
Number of pages6
JournalBiosensors and bioelectronics
Volume85
DOIs
Publication statusPublished - 2016

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Acoustic impedance
Electric Impedance
Electrodes
Microfluidics
Membranes
Equipment and Supplies
Endothelial cells
Microchannels
Blood-Brain Barrier
Visibility
Culture Media
Monolayers
Endothelial Cells
Inspection
Cells
Temperature
Fluids

Cite this

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title = "Direct quantification of transendothelial electrical resistance in organs-on-chips",
abstract = "Measuring transendothelial or transepithelial electrical resistance (TEER) is a widely used method to monitor cellular barrier tightness in organs-on-chips. Unfortunately, integrated electrodes close to the cellular barrier hamper visual inspection of the cells or require specialized cleanroom processes to fabricate see-through electrodes. Out-of-view electrodes inserted into the chip's outlets are influenced by the fluid-filled microchannels with relatively high resistance. In this case, small changes in temperature or medium composition strongly affect the apparent TEER. To solve this, we propose a simple and universally applicable method to directly determine the TEER in microfluidic organs-on-chips without the need for integrated electrodes close to the cellular barrier. Using four electrodes inserted into two channels – two on each side of the porous membrane – and six different measurement configurations we can directly derive the isolated TEER independent of channel properties. We show that this method removes large variation of non-biological origin in chips filled with culture medium. Furthermore, we demonstrate the use of our method by quantifying the TEER of a monolayer of human hCMEC/D3 cerebral endothelial cells, mimicking the blood-brain barrier inside our microfluidic organ-on-chip device. We found stable TEER values of 22 Ω cm2±1.3 Ω cm2 (average ± standard error of the mean of 4 chips), comparable to other TEER values reported for hCMEC/D3 cells in well-established Transwell systems. In conclusion, we demonstrate a simple and robust way to directly determine TEER that is applicable to any organ-on-chip device with two channels separated by a membrane. This enables stable and easily applicable TEER measurements without the need for specialized cleanroom processes and with visibility on the measured cell layer",
author = "{van der Helm}, {Marieke Willemijn} and Mathieu Odijk and Jean-Philippe Frimat and {van der Meer}, {Andries Dirk} and Eijkel, {Jan C.T.} and {van den Berg}, Albert and Segerink, {Loes Irene}",
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Direct quantification of transendothelial electrical resistance in organs-on-chips. / van der Helm, Marieke Willemijn; Odijk, Mathieu; Frimat, Jean-Philippe; van der Meer, Andries Dirk; Eijkel, Jan C.T.; van den Berg, Albert; Segerink, Loes Irene.

In: Biosensors and bioelectronics, Vol. 85, 2016, p. 924-929.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Direct quantification of transendothelial electrical resistance in organs-on-chips

AU - van der Helm, Marieke Willemijn

AU - Odijk, Mathieu

AU - Frimat, Jean-Philippe

AU - van der Meer, Andries Dirk

AU - Eijkel, Jan C.T.

AU - van den Berg, Albert

AU - Segerink, Loes Irene

N1 - eemcs-eprint-27103

PY - 2016

Y1 - 2016

N2 - Measuring transendothelial or transepithelial electrical resistance (TEER) is a widely used method to monitor cellular barrier tightness in organs-on-chips. Unfortunately, integrated electrodes close to the cellular barrier hamper visual inspection of the cells or require specialized cleanroom processes to fabricate see-through electrodes. Out-of-view electrodes inserted into the chip's outlets are influenced by the fluid-filled microchannels with relatively high resistance. In this case, small changes in temperature or medium composition strongly affect the apparent TEER. To solve this, we propose a simple and universally applicable method to directly determine the TEER in microfluidic organs-on-chips without the need for integrated electrodes close to the cellular barrier. Using four electrodes inserted into two channels – two on each side of the porous membrane – and six different measurement configurations we can directly derive the isolated TEER independent of channel properties. We show that this method removes large variation of non-biological origin in chips filled with culture medium. Furthermore, we demonstrate the use of our method by quantifying the TEER of a monolayer of human hCMEC/D3 cerebral endothelial cells, mimicking the blood-brain barrier inside our microfluidic organ-on-chip device. We found stable TEER values of 22 Ω cm2±1.3 Ω cm2 (average ± standard error of the mean of 4 chips), comparable to other TEER values reported for hCMEC/D3 cells in well-established Transwell systems. In conclusion, we demonstrate a simple and robust way to directly determine TEER that is applicable to any organ-on-chip device with two channels separated by a membrane. This enables stable and easily applicable TEER measurements without the need for specialized cleanroom processes and with visibility on the measured cell layer

AB - Measuring transendothelial or transepithelial electrical resistance (TEER) is a widely used method to monitor cellular barrier tightness in organs-on-chips. Unfortunately, integrated electrodes close to the cellular barrier hamper visual inspection of the cells or require specialized cleanroom processes to fabricate see-through electrodes. Out-of-view electrodes inserted into the chip's outlets are influenced by the fluid-filled microchannels with relatively high resistance. In this case, small changes in temperature or medium composition strongly affect the apparent TEER. To solve this, we propose a simple and universally applicable method to directly determine the TEER in microfluidic organs-on-chips without the need for integrated electrodes close to the cellular barrier. Using four electrodes inserted into two channels – two on each side of the porous membrane – and six different measurement configurations we can directly derive the isolated TEER independent of channel properties. We show that this method removes large variation of non-biological origin in chips filled with culture medium. Furthermore, we demonstrate the use of our method by quantifying the TEER of a monolayer of human hCMEC/D3 cerebral endothelial cells, mimicking the blood-brain barrier inside our microfluidic organ-on-chip device. We found stable TEER values of 22 Ω cm2±1.3 Ω cm2 (average ± standard error of the mean of 4 chips), comparable to other TEER values reported for hCMEC/D3 cells in well-established Transwell systems. In conclusion, we demonstrate a simple and robust way to directly determine TEER that is applicable to any organ-on-chip device with two channels separated by a membrane. This enables stable and easily applicable TEER measurements without the need for specialized cleanroom processes and with visibility on the measured cell layer

U2 - 10.1016/j.bios.2016.06.014

DO - 10.1016/j.bios.2016.06.014

M3 - Article

VL - 85

SP - 924

EP - 929

JO - Biosensors and bioelectronics

JF - Biosensors and bioelectronics

SN - 0956-5663

ER -