The aim of this paper is to develop and simulate elastic-perfectly plastic contact theories for proper determination and estimation of contact area in manipulation of micro/nano bioparticles. The nanoparticles studied in this paper are categorized into three different cancerous cell types, lowly (LNCaP) and highly metastatic human prostate cancer cells (CL-1, CL-2), two normal bladder cells (Hu609 and HCV29) and three cancerous bladder cells (Hu456, T24 and BC3726). First, Hertz elastic model, finite element, and Brake and Chang elastic-perfectly plastic models with two different elastic states were simulated for Hu609 and Hu456 cells, and the results were compared against each other. Then, material and geometry effects of particles during contact were taken into account. Additionally, contacts of micro/ nanoparticle–substrate and micro/nanoparticle–atomic force microscope tip were studied. The results of contact simulations indicate a meaningful difference in distinct models. It can be inferred from the difference between Brake and Chang elastic-perfectly plastic models and Hertz theory that the latter is unable to describe the contact behaviour of very soft bioparticles. In most of previous studies, elastic contact theories such as Hertz and JKR have been used to calculate mechanical properties of soft particles manipulation; for the first time, however, two Brake and Chang theories have been used here to calculate the mechanical properties of bioparticles and to simulate the contact mechanics for use in biomanipulation based on the atomic force microscopy.