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This study aims to adoptively reduce the major histocompatibility complex class I (MHC‐I) molecule surface expression of cancer cells by exposure to microfluid shear stress and a monoclonal antibody. A microfluidic system is developed and tumor cells are injected at different flow rates. The bottom surface of the microfluidic system is biofunctionalized with antibodies (W6/32) specific for the MHC‐I molecules with a simple method based on microfluidic protocols. The antibodies promote binding between the bottom surface and the MHC‐I molecules on the tumor cell membrane. The cells are injected at an optimized flow rate, then roll on the bottom surface and are subjected to shear stress. The stress is localized and enhanced on the part of the membrane where MHC‐I proteins are expressed, since they stick to the antibodies of the system. The localized stress allows a stripping effect and consequent reduction of …