title: A single inlet two-stage acoustophoresis chip enabling tumor cell enrichment from white blood cells.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Lund University, Box 118, SE-221 00 Lund, Sweden. maria.antfolk@bme.lth.se per.augustsson@bme.lth.se.
authors.forename: Maria
authors.initials: M
authors.lastname: Antfolk
authors.forename: Christian
authors.initials: C
authors.lastname: Antfolk
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.forename: Thomas
authors.initials: T
authors.lastname: Laurell
authors.forename: Per
authors.initials: P
authors.lastname: Augustsson
mesh_terms: D000162:Acoustics; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D057446:Hydrodynamics; D056656:Lab-On-A-Chip Devices; D007962:Leukocytes / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*