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A Micro-fluidic Approach using  A Micro-fluidic Approach
    a Super-functional Liver Chip
                             using a Super-functional Liver Chip
          Micro-fluidicɹ                                                      Liver                Hepatic



            ˙  Introduction
   Proteomic Analysis of Human  iPS Cell Differentiation  Alternatives to animal testing, i.e., in vitro assay systems, are   lobule

            urgently required for drug, cosmetic and dietary supplement
            development. The liver, a multifunctional organ, is the organ
            primarily responsible for the metabolism and detoxification of
            xenobiotics. Thus, the development of an artificial liver with
            both iPS cells and ES cells has been investigated around the
            world to replace the animal testing.                        Space of Disse   Stellate cell
   Comparative Metabolomics  of Human ES Cells  chip in collaboration with the Tagawa Lab, Tokyo Institute of   Blood flow  Hepatocyte  Endothelial cell
            Shimadzu also has been developing a super-functional liver

            Technology, JAPAN.


                                                                   Kupffer cell

            The above figure shows the structure of liver. Since the hepatic tissue structure includes specific cellular polarities strongly
   A Micro-fluidic Approach using a Super-functional Liver Chip  ɾ Long-term maintenance of liver-specific expressions and functions  Through hole  Compressed Air Room Chamber
            related to the multiple functions of the liver, it is important to use this architecture in the construction of an in vitro system.

            While a hepatocyte chip has been widely investigated, we are developing a hepatic tissue chip, which has the following unique
            features:

            ɾ Flow based chip system allows control of cell culture





   Metabolomics  by LC-MS/MS









                                                                 Diaphragm   Chanel from the   Cavity
                                                                            incubation chamber
                             Chip and alignment jig                   Structure of the pneumatic sampling valve
   Tissue Imaging  by MALDI                             Pneumatic valve   Medium

                                                                           &

                                          Drug


                                                          Filter         Metabolites
                                                                                PDMS
   Shimadzu’s Mass  Spectrometers




                                                                              ECM
                                  Hydrophobic layer

                                                            Endothelial Cells

                                                 Hepatocytes

                                                                             (EHS Gel)

                                              Structure of the super-functional liver chip
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