Abstract
A cancer immunotherapy μ-environment LabChip, equipped with titanium oxide phthalocyanine (TiOPc)-based optoelectronic tweezers (OET) to achieve direct cell–cell contact, was developed in this Ph.D. study and could be applied to study the interaction between immune cells and other cells. One of the applications as demonstrated for the real-time analysis of nature killer (NK) cells' behavior. In microfluidic devices, it is difficult to simultaneously solve the dead zone problems and observe dynamic cell-cell interactions. A stable and static culture μ-environment LabChip was focused and developed in this Ph.D. research to enhance NK cell activities to explore cancer immunotherapy studies. In addition, OET was developed and used to solve the dead zone problems by manipulating a single cell into four-leaf-clover-shaped (FLCS) microwells made of light-activated hydrogel, Poly(ethylene glycol) diacrylate (PEG-DA), through optofluidic maskless lithography, to enhance direct cell-cell contact. This design reconstructed an in vitro human immune system for the studies of dynamic immunological response. When the NK cells came into contact with the target cells in the μ-environment LabChip, the target cells showed apoptotic characteristics (i.e. cell shrinkage and blebbing within 2 h and then die within 3 h). The NK cell activity higher than 7.7%, compared with the NK cell: target (1:1) under the conventional analysis, was demonstrated via the μ-environment LabChip developed in this Ph.D. study. An innovative cancer immunotherapy μ-environment LabChip has been developed to provide a stable and static environment for cell–cell interaction studies. Furthermore, this μ-environment LabChip shows the potential to enhance NK cell activity and to study immunological interactions between immune cells and cancer cells dynamically.