In this paper, the design issues of diagnostic observer-based fault detection (FD) for piecewise affine systems are investigated. To be specific, the diagnostic observer-based FD approaches are developed to satisfy the specified disturbance attenuation and optimize the fault detectability at the same time. Considering the fact that the measurements are generally corrupted with noises or disturbances, the proposed approaches are mainly dedicated to the case that the process and its FD system are non-synchronous in transition from one region to another. Moreover, aiming at improving the FD performance, a mode observer is integrated to relax the design condition for the residual generator. An example is given in the end to show the effectiveness of the proposed approaches.