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Abstract. Navigation and recognition of disease lesions remain challenging during colorectal cancer diagnosis and treatment, given that the precision and capacity of using specific surface antigens as recognition sites are relatively lacking. Moreover, the low penetration rate of noninvasive detection methods has delayed disease diagnosis in developing countries. We developed a bacterial device targeting the Thomsen–Friedenreich antigen, which is abundant on lesion tissue, and produced vesicles that serve as markers for ultrasonic detection. The device uses a bacterial cell surface display system and acoustic reporter gene to function as a screening device for colorectal cancer detection. The diagnostic efficiency of this device was determined by flow cytometry, immunohistochemistry, microfluidic chip-based assay, and ultrasonic examinations on both cellular and tissue scales. In all scales and experiments, our device showed great feasibility upon differentiating disease lesion and normal tissue, while foundation of the usage of vesicle reporter system as noninvasive method has also been laid. The application of this device provides insight into the practicability and prospect of bacterial detecting agents in the field of diagnostics. All animal studies were approved by the Institutional Animal Care and Use Committee of Shanghai Jiao Tong University, China (approval No. 201801015) on February 23, 2018.