Nanoparticles have become widely used materials in various fields, yet their mechanism of action at the cellular level after entering the human body remains unclear. Accurately observing the effect of nanosize dimensions on particle internalization and toxicity in cells is crucial, particularly under the conditions of biological activity. With the aim of helping to study the interactions between nanoparticles of varying sizes and active cell membranes, we propose a flexible biosensor system based on a field effect transistor (FET). We constructed lipid bilayers on the device in vitro to simulate the interaction between nanoparticles and lipid membranes under active conditions, with the aim of investigating the effect of differently sized nanoparticles on the cell membrane. The experimental results revealed that nanoparticles with a diameter smaller than 50 nm tend to induce mild strain and repairable damage to the membrane, whereas nanoparticles larger than 50 nm may cause more severe damage, and even transmembrane penetration, by creating unrecoverable pores. The stretching of the lipid membrane exacerbated the deformation and destruction caused by nanoparticles, even in the case of smaller particles. These above results are consistent with previous theories on the interactions between cell membranes and nanoparticles. The proposed biosensors provide a valuable tool for investigating how the nanosize dimensions of particles affect their ability to penetrate and cause destruction in dynamic cell membranes, contributing to the improvement of a more comprehensive theoretical system for understanding the interaction process between nanoparticles and cell membranes.