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ABSTRACT Microfluidic devices (MDs) present a novel method for detecting circulating tumor cells (CTCs), enhancing the process through targeted techniques and visual inspection. However, current approaches often yield heterogeneous CTC populations, necessitating additional processing for comprehensive analysis and phenotype identification. These procedures are often expensive, time‐consuming, and need to be performed by skilled technicians. In this study, we investigate the potential of a cost‐effective and efficient hyperuniform micropost MD approach for CTC classification. Our approach combines mathematical modeling of fluid–structure interactions in a simulated microfluidic channel with machine learning techniques. Specifically, we developed a cell‐based modeling framework to assess CTC dynamics in erythrocyte‐laden plasma flow, generating a large dataset of CTC trajectories that account for two distinct CTC phenotypes. Convolutional neural network (CNN) and recurrent neural network (RNN) were then employed to analyze the dataset and classify these phenotypes. The results demonstrate the potential effectiveness of the hyperuniform micropost MD design and analysis approach in distinguishing between different CTC phenotypes based on cell trajectory, offering a promising avenue for early cancer detection.