Label-free and non-invasive recovery of circulating tumor cells using an integrated acoustofluidic-SERS chip

Accurate capture and molecular analysis of circulating tumor cells (CTCs) from whole blood are crucial for early cancer diagnosis, prognosis and personalized therapy. Conventional enrichment methods tend to induce cellular damage, compromising cell viability and limiting downstream functional analysis. To address this, we present an Acousto-SERS Integrated Trapping Chip (ASSIT Chip) which combines acoustic sorting with surface enhanced Raman scattering (SERS) fingerprinting for label-free, non-invasive CTC identification and recovery. In this platform, interdigital transducers generate a finely tuned acoustic field that gently sorts CTCs from whole blood via contactless manipulation. The sorted cells are then transported to an integrated SERS region for label-free spectral fingerprinting. From acoustic sorting to optical identification, the fully non-invasive workflow minimizes cellular damage. Additionally, the dual-mode approach integrates physical size selection with chemical biomolecular identification, thus significantly improving the enrichment purity. Through precise control of acoustic and hydrodynamic fields, the ASSIT Chip achieves high sorting efficiency (86.7%) and recovery rate (96.9%). By employing a microsphere-templated plasmonic substrate, label-free SERS detection accurately distinguishes CTCs from blood cells with an accuracy of 96.6%. More importantly, the retrieved CTCs retain high viability and undiminished proliferative capacity, enabling subsequent cell culture and downstream biological studies. The validation with whole blood samples confirms that the ASSIT Chip provides a robust platform for cancer diagnostics and functional CTC analysis, holding considerable promise for clinical translation and personalized medicine.