Reliability is a vital issue in the area of communication. In this paper, we particularly investigate the reliability issue for diffusion‐based molecular communication. First, we present the communication process in system model, where a classified model is further developed at the side of receiver to divide received molecules into signal, inter‐symbol interference, and noise branches. The classified model is used to prove the feasibility and necessity of improving the reliability performance. Second, an adaptive threshold variation (ATV) algorithm is designed to be able to improve the reliability performance that enables the receiver to adapt the channel condition properly through learning process. Furthermore, the complexity of ATV and the performance in various noisy conditions are discussed. An expression of signal to interference plus noise ratio is defined in numerical simulation to verify our goal with variational parameters, as well as with the adoption of ATV algorithm. The results indicate that ATV algorithm works well in general case in improving reliability performance for diffusion‐based molecular communication
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