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This technology uses sub-nanoliter microwells seeded with immune effector cells and target cells to assess the cytotoxic capabilities of individual immune cells. Firstly, immune cells and target cells are seeded in a 1:1 ratio into an array of microwells. Each microwell with a single immune cell and single target cell is monitored for cell death via fluorescence microscopy, and the entire microwell plate can be assayed for immune cell activation by incubating on a glass plate functionalized with antibodies against secreted immune-modulators. Importantly, individual immune cells remain viable, and the immune cells with cytotoxic capacity can be isolated for downstream assays such as RNA analysis or clonal expansion. This technology can be used to study NK cell activation, or to identify and assay rare T-cell clones that are reactive against infected cells or tumor antigens.