Measuring direct current trans-epithelial electrical resistance in organ-on-a-chip microsystems

Mathieu Odijk, Andries Dirk van der Meer, Daniel Levner, Hyun Jung Kim, Marieke Willemijn van der Helm, Loes Irene Segerink, Jean-Philippe Frimat, Geraldine A. Hamilton, Donald E. Ingber, Albert van den Berg

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    Abstract

    Trans-epithelial electrical resistance (TEER) measurements are widely used as real-time, non-destructive, and label-free measurements of epithelial and endothelial barrier function. TEER measurements are ideal for characterizing tissue barrier function in organs-on-chip studies for drug testing and investigation of human disease models; however, published reports using this technique have reported highly conflicting results even with identical cell lines and experimental setups. The differences are even more dramatic when comparing measurements in conventional Transwell systems with those obtained in microfluidic systems. Our goal in this work was therefore to enhance the fidelity of TEER measurements in microfluidic organs-on-chips, specifically using direct current (DC) measurements of TEER, as this is the most widely used method reported in the literature. Here we present a mathematical model that accounts for differences measured in TEER between microfluidic chips and Transwell systems, which arise from differences in device geometry. The model is validated by comparing TEER measurements obtained in a microfluidic gut-on-a-chip device versus in a Transwell culture system. Moreover, we show that even small gaps in cell coverage (e.g., 0.4%) are sufficient to cause a significant (similar to 80%) drop in TEER. Importantly, these findings demonstrate that TEER measurements obtained in microfluidic systems, such as organs-on-chips, require special consideration, specifically when results are to be compared with measurements obtained from Transwell systems.
    Original languageUndefined
    Pages (from-to)745-752
    Number of pages8
    JournalLab on a chip
    Volume15
    Issue number3
    DOIs
    Publication statusPublished - 2015

    Keywords

    • EWI-25998
    • METIS-312592
    • IR-95931

    Cite this

    Odijk, Mathieu ; van der Meer, Andries Dirk ; Levner, Daniel ; Kim, Hyun Jung ; van der Helm, Marieke Willemijn ; Segerink, Loes Irene ; Frimat, Jean-Philippe ; Hamilton, Geraldine A. ; Ingber, Donald E. ; van den Berg, Albert. / Measuring direct current trans-epithelial electrical resistance in organ-on-a-chip microsystems. In: Lab on a chip. 2015 ; Vol. 15, No. 3. pp. 745-752.
    @article{7749022b3fe14b53a81e301449075cd8,
    title = "Measuring direct current trans-epithelial electrical resistance in organ-on-a-chip microsystems",
    abstract = "Trans-epithelial electrical resistance (TEER) measurements are widely used as real-time, non-destructive, and label-free measurements of epithelial and endothelial barrier function. TEER measurements are ideal for characterizing tissue barrier function in organs-on-chip studies for drug testing and investigation of human disease models; however, published reports using this technique have reported highly conflicting results even with identical cell lines and experimental setups. The differences are even more dramatic when comparing measurements in conventional Transwell systems with those obtained in microfluidic systems. Our goal in this work was therefore to enhance the fidelity of TEER measurements in microfluidic organs-on-chips, specifically using direct current (DC) measurements of TEER, as this is the most widely used method reported in the literature. Here we present a mathematical model that accounts for differences measured in TEER between microfluidic chips and Transwell systems, which arise from differences in device geometry. The model is validated by comparing TEER measurements obtained in a microfluidic gut-on-a-chip device versus in a Transwell culture system. Moreover, we show that even small gaps in cell coverage (e.g., 0.4{\%}) are sufficient to cause a significant (similar to 80{\%}) drop in TEER. Importantly, these findings demonstrate that TEER measurements obtained in microfluidic systems, such as organs-on-chips, require special consideration, specifically when results are to be compared with measurements obtained from Transwell systems.",
    keywords = "EWI-25998, METIS-312592, IR-95931",
    author = "Mathieu Odijk and {van der Meer}, {Andries Dirk} and Daniel Levner and Kim, {Hyun Jung} and {van der Helm}, {Marieke Willemijn} and Segerink, {Loes Irene} and Jean-Philippe Frimat and Hamilton, {Geraldine A.} and Ingber, {Donald E.} and {van den Berg}, Albert",
    note = "eemcs-eprint-25998",
    year = "2015",
    doi = "10.1039/c4lc01219d",
    language = "Undefined",
    volume = "15",
    pages = "745--752",
    journal = "Lab on a chip",
    issn = "1473-0197",
    publisher = "Royal Society of Chemistry",
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    }

    Measuring direct current trans-epithelial electrical resistance in organ-on-a-chip microsystems. / Odijk, Mathieu; van der Meer, Andries Dirk; Levner, Daniel; Kim, Hyun Jung; van der Helm, Marieke Willemijn; Segerink, Loes Irene; Frimat, Jean-Philippe; Hamilton, Geraldine A.; Ingber, Donald E.; van den Berg, Albert.

    In: Lab on a chip, Vol. 15, No. 3, 2015, p. 745-752.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Measuring direct current trans-epithelial electrical resistance in organ-on-a-chip microsystems

    AU - Odijk, Mathieu

    AU - van der Meer, Andries Dirk

    AU - Levner, Daniel

    AU - Kim, Hyun Jung

    AU - van der Helm, Marieke Willemijn

    AU - Segerink, Loes Irene

    AU - Frimat, Jean-Philippe

    AU - Hamilton, Geraldine A.

    AU - Ingber, Donald E.

    AU - van den Berg, Albert

    N1 - eemcs-eprint-25998

    PY - 2015

    Y1 - 2015

    N2 - Trans-epithelial electrical resistance (TEER) measurements are widely used as real-time, non-destructive, and label-free measurements of epithelial and endothelial barrier function. TEER measurements are ideal for characterizing tissue barrier function in organs-on-chip studies for drug testing and investigation of human disease models; however, published reports using this technique have reported highly conflicting results even with identical cell lines and experimental setups. The differences are even more dramatic when comparing measurements in conventional Transwell systems with those obtained in microfluidic systems. Our goal in this work was therefore to enhance the fidelity of TEER measurements in microfluidic organs-on-chips, specifically using direct current (DC) measurements of TEER, as this is the most widely used method reported in the literature. Here we present a mathematical model that accounts for differences measured in TEER between microfluidic chips and Transwell systems, which arise from differences in device geometry. The model is validated by comparing TEER measurements obtained in a microfluidic gut-on-a-chip device versus in a Transwell culture system. Moreover, we show that even small gaps in cell coverage (e.g., 0.4%) are sufficient to cause a significant (similar to 80%) drop in TEER. Importantly, these findings demonstrate that TEER measurements obtained in microfluidic systems, such as organs-on-chips, require special consideration, specifically when results are to be compared with measurements obtained from Transwell systems.

    AB - Trans-epithelial electrical resistance (TEER) measurements are widely used as real-time, non-destructive, and label-free measurements of epithelial and endothelial barrier function. TEER measurements are ideal for characterizing tissue barrier function in organs-on-chip studies for drug testing and investigation of human disease models; however, published reports using this technique have reported highly conflicting results even with identical cell lines and experimental setups. The differences are even more dramatic when comparing measurements in conventional Transwell systems with those obtained in microfluidic systems. Our goal in this work was therefore to enhance the fidelity of TEER measurements in microfluidic organs-on-chips, specifically using direct current (DC) measurements of TEER, as this is the most widely used method reported in the literature. Here we present a mathematical model that accounts for differences measured in TEER between microfluidic chips and Transwell systems, which arise from differences in device geometry. The model is validated by comparing TEER measurements obtained in a microfluidic gut-on-a-chip device versus in a Transwell culture system. Moreover, we show that even small gaps in cell coverage (e.g., 0.4%) are sufficient to cause a significant (similar to 80%) drop in TEER. Importantly, these findings demonstrate that TEER measurements obtained in microfluidic systems, such as organs-on-chips, require special consideration, specifically when results are to be compared with measurements obtained from Transwell systems.

    KW - EWI-25998

    KW - METIS-312592

    KW - IR-95931

    U2 - 10.1039/c4lc01219d

    DO - 10.1039/c4lc01219d

    M3 - Article

    VL - 15

    SP - 745

    EP - 752

    JO - Lab on a chip

    JF - Lab on a chip

    SN - 1473-0197

    IS - 3

    ER -