In the paper, we proposed two new highly sensitive and compact biosensors with ultra-high-quality factors based on the 1-D binary photonic crystal (silicon/air thin layer) with a defect layer. The proposed asymmetric and symmetric biosensors have just a few periods (two to five) on both sides of the defect layer and the normal cell group (INOK) and cancer cells group (YD-10B) are considered for the studies. The effects of different parameters including silicon layer thickness, air layer thickness, defect layer thickness, substrate position, number of periods, and light incident angle are considered in the biosensor operation and the biosensors are optimized based on the sensitivity. The results demonstrate that the sensitivity and defect mode wavelength of the sensors are independent of the substrate position. However, the quality factor and FOM of the sensors significantly depend on the substrate position and they are improved significantly in the symmetric sensor (~ 37% improvement in optimum condition). Also, the high sensitivities of the sensors are maintained over a wide range of silicon and air thicknesses, which is a valuable achievement in the manufacturing process. Furthermore, the sensitivity of the optimized biosensors with a defect layer thickness of 10 microns and only two periods reaches S ~ 2811 nm/RIU which is an excellent sensitivity for an optical biosensor.