Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is approximate to 90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p < 0.001) than that using a conventional biomarker (carcinoembryonic antigen (CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.

Automated summary

In this study, a 3D porous sponge microfluidic chip with an exosome enrichment platform was constructed, achieving a capture efficiency of approximately 90%. A specific exosome membrane protein (SORL1) for colorectal cancer was identified through deep mass spectrometry analysis, and a specific quantum dot labeling method for SORL1 detection was developed. An ensemble classification system was established using features extracted from 64-patched fluorescence images, and it showed a significantly higher area under the curve (AUC) of 0.99 compared to the conventional biomarker carcinoembryonic antigen (CEA) with an AUC of 0.71. This system demonstrated similar diagnostic performance for early-stage CRC, young CRC, and CEA-negative CRC patients.