Acoustofluidic, Label-Free Separation and Simultaneous Concentration of Rare Tumor Cells from White Blood Cells

Enrichment of rare cells from peripheral blood has emerged as a means to enable noninvasive diagnostics and development of personalized drugs, commonly associated with a prerequisite to concentrate the enriched rare cell population prior to molecular analysis or culture. However, common concentration by centrifugation has important limitations when processing low cell numbers. Here, we report on an integrated acoustophoresis-based rare cell enrichment system combined with integrated concentration. Polystyrene 7 gm microparticles could be separated from 5,mu m particles with a recovery of 99.3 +/- 0.3% at a contamination of 0.1 +/- 0.03%, with an overall 25.7 +/- 1.7-fold concentration of the recovered 7 gm particles. At a flow rate of 100 mu L/min, breast cancer cells (MCF7) spiked into red blood cell-lysed human blood were separated with an efficiency of 91.8 +/- 1.0% with a contamination of 0.6 +/- 0.1% from white blood cells with a 23.8 +/- 1.3-fold concentration of cancer cells. The recovery of prostate cancer cells (DU145) spiked into whole blood was 84.1 +/- 2.1% with 0.2 +/- 0.04% contamination of white blood cells with a 9.6 +/- 0.4-fold concentration of cancer cells. This simultaneous on-chip separation and concentration shows feasibility of future acoustofluidic systems for rapid label-free enrichment and molecular characterization of circulating tumor cells using peripheral venous blood in clinical practice.