Effective enrichment of trace exosomes for the label-free SERS detection via low-cost thermophoretic profiling

Exosome-based liquid biopsies possess great potential in monitoring cancer development However, current exosome detection biosensors require large exosome volumes, showing the weak detection sensitivity. Besides, these methods pay little attention to in situ analysis of exosomes, hence limiting the provision of more accurate clinically-relevant information. Herein, we develop an innovative label-free biosensor combining the low-cost thermophoretic enrichment method with the surface-enhanced Raman spectroscopy (SERS) detection. Based on the thermophoretic enrichment strategy, exosomes and gold nanoparticles can be enriched together into a small area with a scale of 500 μm within 10 min. The Raman signals of various exosomes derived from normal, cancerous cell lines and human serum are dynamically monitored in situ, with the limit of detection of 10²-10³ particles per microliter, presenting higher sensitivity compared with the similar label-free SERS detection. The spectral data set of different exosomes is applied to train for multivariate classification of cell types and to estimate how the normal exosome data resemble cancer cell exosome. The reliable classification and identification of different exosomes can be realized. The current biosensor is convenient, low-cost and requires small exosome volumes (∼3 μL), and if validated in larger cohorts may contribute to the tumor prediction and diagnosis.