Micro/Nanostructured Materials and Microfluidic Diagnostic Platforms Enable Multimodal Detection of Circulating Tumor Cells.

Abstract

Circulating tumor cells (CTCs), as pivotal targets in liquid biopsy, offer dynamic, multidimensional insights into tumor heterogeneity and metastatic progression. However, their extreme rarity, pronounced heterogeneity, and the complexity of the blood microenvironment severely constrain detection accuracy. Advances in micro/nanomaterials and functional device engineering have enabled substantial improvements in CTC enrichment efficiency by refining the topographical and chemical properties of capture interfaces. These innovations also provide a compatible foundation for multimodal molecular profiling. This review systematically outlines the structure-function relationships of functionalized nanomaterials, microfiltration substrates, and biomimetic microfluidic devices, highlighting how material parameters-such as nanoscale architectures and membrane pore sizes-govern CTC capture performance. We further explore the integration of micro/nanomaterials with functional platforms for multidimensional molecular analyses across DNA, RNA, and protein levels. Coupled with emerging digital PCR technologies, these systems show promise in overcoming the sensitivity barriers associated with rare mutation detection and protein quantification, enabling multi-omics data fusion. We also discuss how artificial intelligence (AI)-driven feature selection, clustering, and prediction integrate multidimensional data to decode tumor heterogeneity and guide disease monitoring. Despite rapid progress, key challenges remain-including the lack of standardization, limited integration of multi-omic datasets, and the need for robust clinical validation. Future directions may lie in the convergence of microfluidic-integrated materials, single-cell multi-omics, and AI-driven analytics to establish dynamic, high-resolution monitoring platforms that bridge the gap between fundamental research and clinical precision oncology.