Cell sorting using targeted biotinylated albumin microbubbles

Cell analysis often requires isolation of certain cell types. Various separating methods have been applied to cell sorting, including florescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS). However, these conventional approaches need to exert additional force on the cell, thus facing the risk of cell damage. In this study, we hypothesize that biotinylated albumin microbubbles (MBs) conjugated with antibodies (i.e., targeted MBs, or tMBs) can be used for cell separation from the solution by buoyancy of the MBs. Specifically, biotin is conjugated to the albumin shell by covalent bond (biotin-MBs) to strengthen the interaction between albumin shell and the antibodies. The results show that only the targeted biotin-MBs sort the MDA-MB-231 cells, in which the cell umber of the upper suspension (about 137.5×10⁴ cells/mL) is six times higher than the one of the pellet (23.5×10⁴ cells/mL). Biotinylation of MBs without conjugation of antibodies does not sort the cells with only 7×10⁴ cells/mL in the upper suspension and most of the cells (241.5×10⁴ cells/mL) deposit as the pellet. Control MBs fail to sort the cells with or without avidin and antibodies. Our biotinylated albumin MBs conjugated with specific tags successfully separated cells. Furthermore, the sorted cells can be recovered by ultrasound-assisted microbubble desctruction.