A single inlet two-stage acoustophoresis chip enabling tumor cell enrichment from white blood cells†
Metastatic disease is responsible for most cancer deaths, and hematogenous spread through circulating tumor cells (CTC) is a prerequisite for tumor dissemination. CTCs may undergo epithelial–mesenchymal transition where many epithelial cell characteristics are lost. Therefore, CTC isolation systems relying on epithelial cell markers are at risk of losing important subpopulations of cells. Here, a simple acoustophoresis-based cell separation instrument is presented. Cells are uniquely separated while maintained in their initial suspending medium, thus eliminating the need for a secondary cell-free medium to hydrodynamically pre-position them before the separation. When characterizing the system using polystyrene particles, 99.6 ± 0.2% of 7 μm diameter particles were collected through one outlet while 98.8 ± 0.5% of 5 μm particles were recovered through a second outlet. Prostate cancer cells (DU145) spiked into blood were enriched from white blood cells at a sample flow rate of 100 μL min−1 providing 86.5 ± 6.7% recovery of the cancer cells with 1.1 ± 0.2% contamination of white blood cells. By increasing the acoustic intensity a recovery of 94.8 ± 2.8% of cancer cells was achieved with 2.2 ± 0.6% contamination of white blood cells. The single inlet approach makes this instrument insensitive to acoustic impedance mismatch; a phenomenon reported to importantly affect accuracy in multi-laminar flow stream acoustophoresis. It also offers a possibility of concentrating the recovered cells in the chip, as opposed to systems relying on hydrodynamic pre-positioning which commonly dilute the target cells.