Molecular Recognition and Topological Matching of CTCs on the Novel Bioinspired Hierarchically Functional Interface with SERS-Microfluidic Sensors

Accurate capture and analysis of circulating tumor cells (CTCs) from cancer patients' blood are crucial for early diagnosis, prognosis, and personalized therapy of cancer. However, it is a significant challenge to develop an efficient and cost-effective method for the isolation and analysis of CTCs from a complex peripheral blood. Herein, we developed a novel microfluidic platform integrated with SU-8 nanodendritic pyramidal microcone array deposition of gold film (SNPMA/Au) substrate for the multistage capture of CTCs and in situ single-cell heterogeneity analysis using the surface-enhanced Raman scattering (SERS) technology. The staggered pyramid structure greatly increased the collision probability between the substrate and CTCs, while nanodendritic structure with aptamer modification on the surface of SNPMA/Au provided conditions for cancer cell attachment, which thereby realized the efficient capture (90.6% ± 4.5%). The pre-enrichment chamber of the chip was designed to increase the concentration of cancer cells, simultaneously reducing the movement rate of CTCs into the capture chamber. Finally, the SERS-microfluidic platform is capable of the efficient capture of CTCs from whole blood, and biomarkers expressed on cancer cells can be readily identified through SERS mapping technology. Therefore, the cellular heterogeneity can be highlighted through variations of biomarker distribution and expression levels. With the successful capture and detection of CTCs in a clinical sample by this platform, it is anticipated that this technology could serve a crucial role in the rapid and sensitive diagnosis of cancer diseases in clinical applications.