Oxidation and adduct formation of xenobiotics in a microfluidic electrochemical cell with boron doped diamond electrodes and an integrated passive gradient rotation mixer

Floris Teunis Gerardus van den Brink, Tina Wigger, Liwei Ma, Mathieu Odijk, Wouter Olthuis, U. Karst, Albert van den Berg

    Research output: Contribution to journalArticleAcademicpeer-review

    5 Citations (Scopus)
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    Abstract

    Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein adduct formation of xenobiotics in a purely instrumental approach. The newly developed microfluidic device enables both the generation of reactive metabolites through electrochemical oxidation and subsequent adduct formation with biomolecules in a chemical microreactor. This allows us to study the detoxification of reactive species with glutathione and to predict potential toxicity of xenobiotics as a result of protein modification. Efficient mixing in microfluidic systems is a slow process due to the typically laminar flow conditions in shallow channels. Therefore, a passive gradient rotation micromixer has been designed that is capable of mixing liquids efficiently in a 790 pL volume within tens of milliseconds. The mixing principle relies on turning the concentration gradient that is initially established by bringing together two streams of liquid, to take advantage of the short diffusion distances in the shallow microchannels of thin-layer flow cells. The mixer is located immediately downstream of the working electrode of an electrochemical cell with integrated boron doped diamond electrodes. In conjunction with mass spectrometry, the two microreactors integrated in a single device provide a powerful tool to study the metabolism and toxicity of xenobiotics, which was demonstrated by the investigation of the model compound 1-hydroxypyrene.
    Original languageUndefined
    Pages (from-to)3990-4001
    Number of pages12
    JournalLab on a chip
    Volume16
    Issue number20
    DOIs
    Publication statusPublished - 2016

    Keywords

    • EWI-27564
    • IR-103129
    • METIS-320933

    Cite this

    @article{6248800cbe42431e8c4d8e1127431c63,
    title = "Oxidation and adduct formation of xenobiotics in a microfluidic electrochemical cell with boron doped diamond electrodes and an integrated passive gradient rotation mixer",
    abstract = "Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein adduct formation of xenobiotics in a purely instrumental approach. The newly developed microfluidic device enables both the generation of reactive metabolites through electrochemical oxidation and subsequent adduct formation with biomolecules in a chemical microreactor. This allows us to study the detoxification of reactive species with glutathione and to predict potential toxicity of xenobiotics as a result of protein modification. Efficient mixing in microfluidic systems is a slow process due to the typically laminar flow conditions in shallow channels. Therefore, a passive gradient rotation micromixer has been designed that is capable of mixing liquids efficiently in a 790 pL volume within tens of milliseconds. The mixing principle relies on turning the concentration gradient that is initially established by bringing together two streams of liquid, to take advantage of the short diffusion distances in the shallow microchannels of thin-layer flow cells. The mixer is located immediately downstream of the working electrode of an electrochemical cell with integrated boron doped diamond electrodes. In conjunction with mass spectrometry, the two microreactors integrated in a single device provide a powerful tool to study the metabolism and toxicity of xenobiotics, which was demonstrated by the investigation of the model compound 1-hydroxypyrene.",
    keywords = "EWI-27564, IR-103129, METIS-320933",
    author = "{van den Brink}, {Floris Teunis Gerardus} and Tina Wigger and Liwei Ma and Mathieu Odijk and Wouter Olthuis and U. Karst and {van den Berg}, Albert",
    note = "10.1039/c6lc00708b",
    year = "2016",
    doi = "10.1039/c6lc00708b",
    language = "Undefined",
    volume = "16",
    pages = "3990--4001",
    journal = "Lab on a chip",
    issn = "1473-0197",
    publisher = "Royal Society of Chemistry",
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    }

    Oxidation and adduct formation of xenobiotics in a microfluidic electrochemical cell with boron doped diamond electrodes and an integrated passive gradient rotation mixer. / van den Brink, Floris Teunis Gerardus; Wigger, Tina; Ma, Liwei; Odijk, Mathieu; Olthuis, Wouter; Karst, U.; van den Berg, Albert.

    In: Lab on a chip, Vol. 16, No. 20, 2016, p. 3990-4001.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Oxidation and adduct formation of xenobiotics in a microfluidic electrochemical cell with boron doped diamond electrodes and an integrated passive gradient rotation mixer

    AU - van den Brink, Floris Teunis Gerardus

    AU - Wigger, Tina

    AU - Ma, Liwei

    AU - Odijk, Mathieu

    AU - Olthuis, Wouter

    AU - Karst, U.

    AU - van den Berg, Albert

    N1 - 10.1039/c6lc00708b

    PY - 2016

    Y1 - 2016

    N2 - Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein adduct formation of xenobiotics in a purely instrumental approach. The newly developed microfluidic device enables both the generation of reactive metabolites through electrochemical oxidation and subsequent adduct formation with biomolecules in a chemical microreactor. This allows us to study the detoxification of reactive species with glutathione and to predict potential toxicity of xenobiotics as a result of protein modification. Efficient mixing in microfluidic systems is a slow process due to the typically laminar flow conditions in shallow channels. Therefore, a passive gradient rotation micromixer has been designed that is capable of mixing liquids efficiently in a 790 pL volume within tens of milliseconds. The mixing principle relies on turning the concentration gradient that is initially established by bringing together two streams of liquid, to take advantage of the short diffusion distances in the shallow microchannels of thin-layer flow cells. The mixer is located immediately downstream of the working electrode of an electrochemical cell with integrated boron doped diamond electrodes. In conjunction with mass spectrometry, the two microreactors integrated in a single device provide a powerful tool to study the metabolism and toxicity of xenobiotics, which was demonstrated by the investigation of the model compound 1-hydroxypyrene.

    AB - Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein adduct formation of xenobiotics in a purely instrumental approach. The newly developed microfluidic device enables both the generation of reactive metabolites through electrochemical oxidation and subsequent adduct formation with biomolecules in a chemical microreactor. This allows us to study the detoxification of reactive species with glutathione and to predict potential toxicity of xenobiotics as a result of protein modification. Efficient mixing in microfluidic systems is a slow process due to the typically laminar flow conditions in shallow channels. Therefore, a passive gradient rotation micromixer has been designed that is capable of mixing liquids efficiently in a 790 pL volume within tens of milliseconds. The mixing principle relies on turning the concentration gradient that is initially established by bringing together two streams of liquid, to take advantage of the short diffusion distances in the shallow microchannels of thin-layer flow cells. The mixer is located immediately downstream of the working electrode of an electrochemical cell with integrated boron doped diamond electrodes. In conjunction with mass spectrometry, the two microreactors integrated in a single device provide a powerful tool to study the metabolism and toxicity of xenobiotics, which was demonstrated by the investigation of the model compound 1-hydroxypyrene.

    KW - EWI-27564

    KW - IR-103129

    KW - METIS-320933

    U2 - 10.1039/c6lc00708b

    DO - 10.1039/c6lc00708b

    M3 - Article

    VL - 16

    SP - 3990

    EP - 4001

    JO - Lab on a chip

    JF - Lab on a chip

    SN - 1473-0197

    IS - 20

    ER -