Advanced materials and chemo-specific designs at the nano- and micrometer scale have ensured revolutionary progress in next-generation clinically relevant technologies. For example, isolating a rare population of cells, such as circulating tumor cells (CTCs) from blood among billions of other blood cells, is one of the most complex scientific challenges in cancer diagnostics. Achieving this level of exceptional specificity for extracellular biomarker interactions requires chemical tunability through the use of advanced materials and multistep reactions in both solution and insoluble states.

This review delineates the chemo-specific substrates, chemical methods, and structure–activity relationships (SARs) of chemical platforms used for the isolation and enumeration of CTCs, thereby advancing the relevance of liquid biopsy in cancer diagnostics and disease management. We highlight the synthesis of cell-specific, tumor biomarker-based chemo-specific substrates utilizing functionalized linkers through chemistry-based conjugation strategies.

The capacity of these nano- and micro-scale substrates to enhance interaction specificity and efficiency with targeted tumor cells is discussed in detail. Furthermore, this review emphasizes the importance of CTC capture and downstream processes involving genotypic and phenotypic CTC analysis in real time. These approaches enable early detection of metastasis progression, evaluation of chemotherapy treatment response, and monitoring of progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) in cancer patients.

Royal Society of chemistry.