Microfluidic Platform for the Detection of Single Cell Immune Activity and Tag-Free Selection of Individual Target-Cell Responsive Effector Cells

Abstract

Adoptive Immunotherapy has long been explored as a possible cure for challenging diseases including cancer and HIV infection. The key step in such therapies is to identify and select disease-specific effector cells, which in the past have relied on well-plate based bulk manipulations. But as effector cells against a specific disease are often scarce, bulk studies are ineffective at identifying and selecting the rare effector cells with accuracy. It also takes weeks to prepare a desired population. Though recent advances such as genetically engineered T cell technology and the mutation selection technology have shown great promises, the former is limited by the difficulty in identifying the receptor and antigen, the latter is limited by the direct cell surface fluorescent tagging which could impairs the functional epitomes of surface activation marker and the ineffectiveness of the surface activation marker based selection. Thus I developed a microfluidic system to identify and select effector cells with unprecedented accuracy and speed, by probing the dynamic single cell immune response through co assessing single cell cytokine secretion and cytolysis in picoliter droplets.