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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A microfluidic-based neurotoxin concentration gradient for the generation of an <italic>in vitro</italic>
model of Parkinson’s disease</title>
<author><name sortKey="Seidi, Azadeh" sort="Seidi, Azadeh" uniqKey="Seidi A" first="Azadeh" last="Seidi">Azadeh Seidi</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaji, Hirokazu" sort="Kaji, Hirokazu" uniqKey="Kaji H" first="Hirokazu" last="Kaji">Hirokazu Kaji</name>
<affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a3">Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Annabi, Nasim" sort="Annabi, Nasim" uniqKey="Annabi N" first="Nasim" last="Annabi">Nasim Annabi</name>
<affiliation><nlm:aff id="a4">School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, New South Wales 2006, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ostrovidov, Serge" sort="Ostrovidov, Serge" uniqKey="Ostrovidov S" first="Serge" last="Ostrovidov">Serge Ostrovidov</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ramalingam, Murugan" sort="Ramalingam, Murugan" uniqKey="Ramalingam M" first="Murugan" last="Ramalingam">Murugan Ramalingam</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a5">Faculte de Medecine, National Institute of Health and Medical Research U977, Université de Strasbourg, Strasbourg, Cedex 67085, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Khademhosseini, Ali" sort="Khademhosseini, Ali" uniqKey="Khademhosseini A" first="Ali" last="Khademhosseini">Ali Khademhosseini</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a6">Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21799720</idno>
<idno type="pmc">3145239</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145239</idno>
<idno type="RBID">PMC:3145239</idno>
<idno type="doi">10.1063/1.3580756</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">000679</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000679</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A microfluidic-based neurotoxin concentration gradient for the generation of an <italic>in vitro</italic>
model of Parkinson’s disease</title>
<author><name sortKey="Seidi, Azadeh" sort="Seidi, Azadeh" uniqKey="Seidi A" first="Azadeh" last="Seidi">Azadeh Seidi</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaji, Hirokazu" sort="Kaji, Hirokazu" uniqKey="Kaji H" first="Hirokazu" last="Kaji">Hirokazu Kaji</name>
<affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a3">Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Annabi, Nasim" sort="Annabi, Nasim" uniqKey="Annabi N" first="Nasim" last="Annabi">Nasim Annabi</name>
<affiliation><nlm:aff id="a4">School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, New South Wales 2006, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ostrovidov, Serge" sort="Ostrovidov, Serge" uniqKey="Ostrovidov S" first="Serge" last="Ostrovidov">Serge Ostrovidov</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ramalingam, Murugan" sort="Ramalingam, Murugan" uniqKey="Ramalingam M" first="Murugan" last="Ramalingam">Murugan Ramalingam</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a5">Faculte de Medecine, National Institute of Health and Medical Research U977, Université de Strasbourg, Strasbourg, Cedex 67085, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Khademhosseini, Ali" sort="Khademhosseini, Ali" uniqKey="Khademhosseini A" first="Ali" last="Khademhosseini">Ali Khademhosseini</name>
<affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="a6">Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Biomicrofluidics</title>
<idno type="ISSN">1932-1058</idno>
<idno type="eISSN">1932-1058</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
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<front><div type="abstract" xml:lang="en"><p>In this study, we developed a miniaturized microfluidic-based high-throughput cell toxicity assay to create an <italic>in vitro</italic>
model of Parkinson’s disease (PD). In particular, we generated concentration gradients of 6-hydroxydopamine (6-OHDA) to trigger a process of neuronal apoptosis in pheochromocytoma PC12 neuronal cell line. PC12 cells were cultured in a microfluidic channel, and a concentration gradient of 6-OHDA was generated in the channel by using a back and forth movement of the fluid flow. Cellular apoptosis was then analyzed along the channel. The results indicate that at low concentrations of 6-OHDA along the gradient (i.e., approximately less than 260 μM), the neuronal death in the channel was mainly induced by apoptosis, while at higher concentrations, 6-OHDA induced neuronal death mainly through necrosis. Thus, this concentration appears to be useful for creating an <italic>in vitro</italic>
model of PD by inducing the highest level of apoptosis in PC12 cells. As microfluidic systems are advantageous in a range of properties such as throughput and lower use of reagents, they may provide a useful approach for generating <italic>in vitro</italic>
models of disease for drug discovery applications.</p>
</div>
</front>
</TEI>
<pmc article-type="other"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biomicrofluidics</journal-id>
<journal-title-group><journal-title>Biomicrofluidics</journal-title>
</journal-title-group>
<issn pub-type="ppub">1932-1058</issn>
<issn pub-type="epub">1932-1058</issn>
<publisher><publisher-name>American Institute of Physics</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21799720</article-id>
<article-id pub-id-type="pmc">3145239</article-id>
<article-id pub-id-type="publisher-id">012191BMF</article-id>
<article-id pub-id-type="doi">10.1063/1.3580756</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Special Topic: Microfluidics in Cell Biology and Tissue Engineering (Guest Editor: Ali Khademhosseini)</subject>
</subj-group>
</article-categories>
<title-group><article-title>A microfluidic-based neurotoxin concentration gradient for the generation of an <italic>in vitro</italic>
model of Parkinson’s disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Seidi</surname>
<given-names>Azadeh</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kaji</surname>
<given-names>Hirokazu</given-names>
</name>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="aff" rid="a3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Annabi</surname>
<given-names>Nasim</given-names>
</name>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ostrovidov</surname>
<given-names>Serge</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ramalingam</surname>
<given-names>Murugan</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Khademhosseini</surname>
<given-names>Ali</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="aff" rid="a6">6</xref>
<xref ref-type="author-notes" rid="n1">a)</xref>
</contrib>
<aff id="a1"><label>1</label>
WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</aff>
<aff id="a2"><label>2</label>
Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</aff>
<aff id="a3"><label>3</label>
Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan</aff>
<aff id="a4"><label>4</label>
School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, New South Wales 2006, Australia</aff>
<aff id="a5"><label>5</label>
Faculte de Medecine, National Institute of Health and Medical Research U977, Université de Strasbourg, Strasbourg, Cedex 67085, France</aff>
<aff id="a6"><label>6</label>
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA</aff>
</contrib-group>
<author-notes><fn id="n1"><label>a)</label>
<p>Author to whom correspondence should be addressed. Tel.: +1-617-388-9271. FAX: +1-617-768-8477. Electronic mail: <email>alik@rics.bwh.harvard.edu</email>
.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><month>6</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>29</day>
<month>6</month>
<year>2011</year>
</pub-date>
<volume>5</volume>
<issue>2</issue>
<elocation-id>022214</elocation-id>
<history><date date-type="received"><day>19</day>
<month>1</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>30</day>
<month>3</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2011 American Institute of Physics</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>American Institute of Physics</copyright-holder>
</permissions>
<abstract><p>In this study, we developed a miniaturized microfluidic-based high-throughput cell toxicity assay to create an <italic>in vitro</italic>
model of Parkinson’s disease (PD). In particular, we generated concentration gradients of 6-hydroxydopamine (6-OHDA) to trigger a process of neuronal apoptosis in pheochromocytoma PC12 neuronal cell line. PC12 cells were cultured in a microfluidic channel, and a concentration gradient of 6-OHDA was generated in the channel by using a back and forth movement of the fluid flow. Cellular apoptosis was then analyzed along the channel. The results indicate that at low concentrations of 6-OHDA along the gradient (i.e., approximately less than 260 μM), the neuronal death in the channel was mainly induced by apoptosis, while at higher concentrations, 6-OHDA induced neuronal death mainly through necrosis. Thus, this concentration appears to be useful for creating an <italic>in vitro</italic>
model of PD by inducing the highest level of apoptosis in PC12 cells. As microfluidic systems are advantageous in a range of properties such as throughput and lower use of reagents, they may provide a useful approach for generating <italic>in vitro</italic>
models of disease for drug discovery applications.</p>
</abstract>
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