On-Chip Isolationand Reciprocal Signal AmplificationDetection of Tumor-Derived Exosomes in Dual-Control Microfluidic Device

The detection of exosomes is critical for health monitoring and disease diagnosis. However, their small size and low concentration present significant challenges. In this study, we designed a dual-control microchip integrated with a surface-enhanced Raman scattering (SERS) signal amplification detection method. By employing separate chambers for isolation and detection, this method achieves magnetic separation control and DNA cascade signal amplification with electrokinetic enrichment detection. The magnetic separation step captures and isolates exosomes in a magnetic-controlled reaction chamber, releasing a signal-switching strand that translates exosome recognition into a DNA signal amplification process. The DNA cascade reciprocal signal amplification reaction is performed in an electrokinetic enrichment reaction chamber, significantly improving detection efficiency and signal intensity. In addition, absolute-value coupled data processing reduces background interference. These unique merits enable precise and highly efficient assay of exosomes. This dual-control microchip signal amplification sensor exhibits remarkable sensitivity, rapid detection times, with a detection limit of 10.9 particles/μL and a reaction time of 35 min, and successful application to real sample analysis. The platform offers a viable, accurate, and portable solution for medical point-of-care testing.