Abstract: A novel class of bioreactor apparatuses are disclosed which offer improved performance over prior art designs. The apparatuses circulate nutrient fluid through a bioreactor device, such as a hollow fiber bioreactor cartridge, which is used to culture a colony of cells. The nutrient fluid is refreshed by the controlled addition of fresh fluid and the controlled removal of used fluid through a sterile infusion/extraction device. Cellular by-product yield is enhanced by periodically alternating the direction of nutrient fluid through the bioreactor and by periodically circulating the harvest fluid through the extracapillary region of the bioreactor cartridge.