Geometry Optimization of a Flow-Based Device to Maximize Selectin-Mediated Hematopoietic Stem Cell Enrichment

Rare cell enrichment techniques must selectively capture and successfully retain cells that exist at < 5% in a suspension. We developed a device to capture hematopoietic stem and progenitor cells (HSPCs) from adult bone marrow using immobilized adhesion molecules called selectins in the presence of a flow field. While we continue to optimize the immobilized protein surface and improve the selectivity of the device for HSPCs, it appears to be at the expense of cell recovery. To address this issue, we used experimental and computational methods to identify the hydrodynamic factors that contribute to cell capture, and present new designs for the device that could improve HSPC recovery without affecting the selectivity. We tested KG1a cell recovery using four configurations of tubing — straight cylindrical, helical, flattened and axially pinched, and two cell loading conditions: static and continuous oscillatory. We utilized COMSOL 3.4 finite element modeling software to investigate the path of particles introduced into these geometries, the fluid velocities and local wall shear stresses, and the predicted recovery efficiency based on the number of particles that contact and stick to the walls of the geometries. We found that, experimentally, the highest number of cells were recovered using static cell loading in a straight cylindrical tubing, but we predict that a corrugated or pinched geometry could further increase recovery under desirable flow conditions.