We are developing next generation cell separation for perfusion bioreactores using advanced spiral microfluidic systems. Our unique technology relies solely on internal fluidic (i.e., hydrodynamic) forces in microchannels for cell separation, thus eliminating the need for membrane filters or external force fields. This system is designed to make an improvement for the continuous biomanufacturing industry by resolving problems in existing separation techniques such as fouling, yield, continuous processing, and viability. The design simplicity and single use disposable approach makes this device ideal for in-line integration with other downstream processes in perfusion bioreactors. It can also perform as a microfiltration/fractionation/concentration device for cellular therapy, gene therapy, stem cell, T-cells, and Exosomes.