Abstract:Breast cancer is the most common malignant tumor in women. Unpredictable metastatic relapse is a major reason for treatment failure, recurrence, and even death in breast cancer patients. Circulating tumor cells (CTCs) are defined as tumor cells that detach from the primary tumor and enter the circulatory or lymphatic system. Studies have confirmed that the detection of CTCs can provide important clinical information for the diagnosis, developing treatment strategies, and prognosis assessment of breast cancer. As one of the key targets for liquid biopsies, CTCs can be collected simply by extracting a patient's blood. However, most CTCs die in the circulation, with only a very small number surviving and invading distant organs. The scarcity in numbers, heterogeneity of CTCs, and interference from complex components in blood pose significant challenges to the accurate detection of CTCs. Various detection methods developed based on the biological and physical properties of CTCs often require separation and enrichment of CTCs before detection. However, preprocessing steps like adsorption, washing, and transfer inevitably result in CTC loss. Moreover, time-consuming, complex procedures, and expensive equipment further limit the clinical application of CTC detection. Therefore, there is an urgent need for the development of new detection technologies. Microfluidic technology, characterized by microfabricated structures, has received significant attention and research in recent years. Microfluidic technology allows for precise control of micrometer-scale fluids and cells, making it particularly suitable for detecting rare CTCs. Microfluidic chips offer advantages such as low cost, simplicity of operation, low consumables, high throughput, and real-time detection. Their miniaturization allows for the integration of various detection techniques into a micro-scale platform, providing an efficient platform for the isolation, identification, and characterization of CTCs, contributing to personalized analysis and treatment of cancer patients. Recently, the rise of three dimession (3D) printing technology has provided a more efficient and personalized approach to the fabrication of microfluidic chips, avoiding the complexities and time-consuming aspects of traditional microfluidic device production. Layer-by-layer printed 3D structures will promote higher efficiency and throughput of microfluidic chips, facilitating the successful application of laboratory techniques in clinical settings. This opens up new perspectives for biological and clinical research on tumors and offers unprecedented opportunities for the diagnosis and treatment of breast cancer. In this article, the authors analyze the characteristics of different CTC detection methods in recent years, elucidate the application of microfluidic technology in the detection of breast cancer CTCs, and the cutting-edge technology of 3D-printed microfluidic chips, and provide an outlook on the application prospects of 3D-printed microfluidic chips in the detection of CTCs in breast cancer.