The specific roles of mass transfer and fluid dynamic stresses on endothelial function, important in atherogenesis, are not known. Further, the effects of mass transfer and fluid dynamic stresses are difficult to separate because areas of "abnormal" mass transfer and "abnormal" wall shear stress tend to co-localize (where abnormal is defined as any deviation from the mass transfer rate or wall shear stress present in a long straight artery with the same flow rate and diameter). Our goal was to design a cell culture device which gives maximum separation between areas of abnormal shear stress and areas of abnormal mass transfer. We used design optimization principles to design a helical cell culture device. Using shear stress and mass transfer fields predicted by solving the governing equations, the area of the device which was exposed to low rates of mass transfer and normal levels of wall shear stress was determined. The design optimization method then maximized this area by varying the design variables, resulting in the optimum design. The optimum design had Reynolds number = 50, helical radius = 3.23 and helical pitch = 3.82. The area of the device which was exposed to low rates of mass transfer and regular levels of wall shear stress was about 4.5 times the inlet cross-sectional area of the device or about 5% of the device total internal surface area. An optimum design was successfully determined and the methodology used was shown to be robust. The area of the device which was exposed to low rates of mass transfer and regular levels of wall shear stress occurred in a defined region which should aid further experimental work.