Abstract
Circulating tumor cell (CTC) test is currently used as a biomarker in cancer treatment. Unfortunately, the poor reproducibility and limited sensitivity with the CTC detection have limited its potential impact on clinical application. A reliable automated CTC detection system is therefore needed. We have designed an automated microfluidic chip-based CTC detection system and hypothesize 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 to validate the CTC capturing efficacy in the peripheral blood. The capture rates for spiking test in SKOV3 cells were 48.3% and 89.6% by using anti-EpCAM antibody alone and a combination of anti-EpCAM antibody and anti-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.
Highlights
Despite recent advances in modern medicine, we are still facing many challenges in cancer diagnosis and treatment
Two different enrichment strategies were used for spiking test, including 1:40 biotinylated anti-Epithelial cell adhesion molecule (EpCAM) antibody only, and an antibody cocktail combined with 1:40 biotinylated anti-EpCAM antibody and 0.005 mg/mL biotinylated anti-N-cadherin antibody (Combi)
It can be seen from the scanning electron microscope (SEM) image that there were many microvilli on the surface of the SKOV3 cell, and some microvilli firmly adhered to the nanopillars of V-BioChip (Figure 1c)
Summary
Despite recent advances in modern medicine, we are still facing many challenges in cancer diagnosis and treatment. Tissue biopsy is the only confirmatory diagnostic method for suspicious lesions while invasive exploratory surgery is required for cancer staging. Tissue biopsy has its own limitations due to its invasiveness and the fact that some lesions are in difficult-to-reach areas. Tissue biopsy cannot assess the risk of cancer metastasis, the progression of the cancer, and the response to treatment [1]. It is very difficult to detect small metastatic lesions or minimal residual diseases using even the most advanced imaging technology [2]. There is an urgent need to develop more precise methods to facilitate screening, diagnosis, and treatment of cancers
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