Dynamics of adhering target cells in an antibody-functionalized microchannels
Affinity-based isolation of target cells from a complex suspension, such as circulating tumor cells (CTCs) in blood, has extensively been studied in effort to develop alternative approaches to invasive biopsies for detection, characterization and monitoring of non-haematologic cancers. Current strategies for isolating cancer cells circulating in the blood stream are still limited to complex analytic methodologies that generate very low yield and purity. Here, selective binding of target cells to a biologically functionalized surface, utilizing a microfluidic system, has been investigated; specific interaction between cell receptors and surface ligands is used as a highly selective tool for capturing the target cells. For high performance of such systems, disposal of maximum non-target species is just as important as retention of maximum target species. In this presentation, the fabrication technology of antibody-functionalized microchannels is described and, based on signal detection theory, well defined criteria are introduced for quantitative characterization of the system performance. The specificity of target-cell adherence within these fabricated microdevices is demonstrated. The kinetics and dynamics of cell attachment under shear flow is experimentally and theoretically investigated, and the detachment of captured cells due to hydrodynamic loading is discussed. For enhanced system performance, we employ a unique fluidic scheme combining a slow flow field, for maximum target-cell attachment, followed by a faster flow field, for maximum detachment of non-target cells. This scheme, allowing isolation of target cells from complex mixtures with high sensitivity and high specificity, will be described.