Few optical transducers that are based on surface plasmon resonance and piezoelectric transducers used in acoustic bulk-wave-based biosensors can utilize non-labeled antibodies. Recently, impedance-based immunosensors were proposed for direct measurements (Yang et al., 2004; Radke and Alocilja, 2005). Even if it looks advantageous to use non-labeled antibodies because of low price and simplicity, the major shortcoming of these types of sensors is low sensitivity, which becomes an important limiting factor for E. coli O157:H7 detection. Three examples of direct measurement immunosensors are discussed in this section; surface plasmon resonance, piezoelectric transducer immunosensors, and impedance-based immunosensors.