Detachment of Tumor Cells from a Cell-Binding Probe: Two Approaches

Liquid biopsy is used to obtain information about a disease from a blood sample or other body fluids. In the context of cancer, circulating tumor cells (CTC) can be used as biomarkers to determine the nature of the tumor, its stage of progression, and the efficiency of the administered therapy. However, the low concentration of CTCs in the bloodstream (1–10 cells/mL) is a challenge for their isolation. Therefore, a minimally invasive in vivo cell probe (BMProbe™) was developed that isolates CTCs via antigen-antibody binding directly from the bloodstream. Current investigations focus on the process of detaching bound cells from the probe surface for subsequent cultivation. This article presents two approaches for detaching LNCaP cells from the BMProbe™: enzymatic detachment and detachment through enzymatic treatment with supplementary flow induced shear stress. To determine the volume flow required to gently detach the cells via shear stress, a computational fluid dynamics (CFD) simulation was carried out. The test results demonstrate that 90% of the bound cells can be detached enzymatically within 10 minutes. Furthermore, additional flow treatment did not result in increased detachment rates. It is feasible that the detachment efficiency can be further increased by longer enzymatic incubation times or higher shear stresses. The influence on the integrity of the cells must however be considered.