A Novel Automatic Platform Based on Nanostructured Microfluidic Chip for Isolating and Identification of Circulating Tumor Cells

Abstract

Circulating tumor cell (CTC) is commonly used as biomarker for early detection, prognostication, decision making, and evaluation of the therapeutic efficacy in cancer treatment. Unfortunately, the poor reproducibility and limited sensitivity with the CTC detection have limited its potential impact on clinical management. A reliable automated CTC detection system is therefore needed. We have designed an automated microfluidic chip-based CTC detection system consisting of three main parts: V-BioChip, Cell RevealTM enrichment and staining system, and an automatic scanning and locating system. We hypothesized this novel system can reliably detect CTC from clinical specimens. SKOV3 ovarian cancer cell line was used first to test the reliability of our system. Ten healthy volunteers, 5 patients with benign ovarian tumors, and 8 patients with epithelial ovarian cancer (EOC) were recruited after obtaining written consents to validate the CTC capturing efficacy in the peripheral blood. The capture rates for spiking test in SKOV3 cells were as 48.3% and 89.6% using EpCAM antibody alone and a combined EpCAM antibody and N-cadherin antibody, respectively. The system was sensitive to detection of low cell count and showed a linear relationship with the cell counts in our test range. The sensitivity and specificity were 62.5% and 100% when CTC was used as a biomarker for EOC. Our results demonstrated that this automatic CTC platform has a high capture rate and is feasible for detection of CTCs in EOC.