Chemotherapy may control but rarely cure metastatic cancers. Remarkably, modern immunotherapies, including cell-based therapies, have cured metastatic melanomas and other types of cancers. A major challenge for all cell therapies in general is the need to develop cost-effective and efficient manufacturing and delivery capabilities. We have recently established an innovative cell isolation technology by applying targeted microbubbles, which have a number of interesting properties that are ideal for bulk cell isolation. Here we propose a simple and cost-efficient system to enrich cells of interest that require multiple markers to identify by integrating these features. When this project is successful, a closed automated system using only a single container will be developed and manufactured for cell isolation, expansion and manipulation.