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A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

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Gautham Vivek Sridharan

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

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Inna Golberg

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

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Ljupcho Prodanov

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

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William J. McCarty

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

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Osman Berk Usta

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

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Rohit Jindal

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

E-mail Address: RJINDAL@mgh.harvard.edu

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, and

Martin L. Yarmush

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA.

E-mail Address: ireis@sbi.org

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https://doi.org/10.1142/S2339547815200034Cited by:8 (Source: Crossref)

Abstract

To evaluate drug and metabolite efficacy on a target organ, it is essential to include metabolic function of hepatocytes, and to evaluate metabolite influence on both hepatocytes and the target of interest. Herein, we have developed a two-chamber microfabricated device separated by a membrane enabling communication between hepatocytes and cancer cells. The microscale environment created enables cell co-culture in a low media-to-cell ratio leading to higher metabolite formation and rapid accumulation, which is lost in traditional plate cultures or other interconnected models due to higher culture volumes. We demonstrate the efficacy of this system by metabolism of tegafur by hepatocytes resulting in cancer cell toxicity.

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