title: A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity.
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.
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
authors.forename: Shyam Sundhar
authors.initials: SS
authors.lastname: Bale
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
authors.forename: Gautham Vivek
authors.initials: GV
authors.lastname: Sridharan
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Golberg
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
authors.forename: Ljupcho
authors.initials: L
authors.lastname: Prodanov
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: McCarty
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
authors.forename: Osman Berk
authors.initials: OB
authors.lastname: Usta
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Jindal
authors.affiliation: 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.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush