Integrated Multi-Channel Automatic Cellular Profiling (iMAP) System for Cholangiocarcinoma Diagnosis

Abstract

Cholangiocarcinoma (CCA) is a highly lethal malignant tumor with a five-year survival rate below 10%. Clinical challenges include the absence of effective screening tools, the gradual progression until symptoms manifest, and the low diagnostic accuracy of CCA tissue due to the paucicellular nature of specimens obtained during an intervention. To address these challenges, an integrated multi-channel automatic cellular profiling (iMAP) system is developed for robust analysis of endoscopically obtained biliary specimens. Brushing cytology samples are introduced into a microfluidic chip to enrich and capture suspicious epithelial cells while eliminating blood and fibrotic cells. The captured cells are subsequently immunostained with fluorescent antibodies for further molecular analysis. The entire process, from sample loading to diagnosis, is fully automated and completed within 30 min. After validating the system with in vitro cell lines, iMAP is applied to analyze clinical brush specimens. In a pilot clinical study with 56 patient samples, good clinical diagnostic accuracy (AUC = 0.85) is demonstrated for CCA using a four-marker combination (MUC1, EpCAM, EGFR, and MARS1). The fully automated iMAP can serve as a complementary technology to the existing clinical cytopathology workflow, thereby minimizing sample loss and enhancing diagnostic accuracy through multiplexing.