Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device. Efficient capture of HCC CTCs originates from the small dimensions of microfluidic channels and enhanced local topographic interactions between the microfluidic channel and extracellular extensions. With the optimized conditions, a capture yield reached > 85% for artificial CTC blood samples. Clinical utility of the system was further validated. CTCs were detected in all the examined 36 patients with HCC, with an average of 14 ± 10/2 mL. On the contrary, no CTCs were detected in healthy, benign liver disease or non-HCC cancer subjects. The current study also successfully demonstrated that the captured CTCs on our CTC-chip were readily released with ethylene diamine tetraacetic acid (EDTA); released CTCs remained alive and could be expanded to form a spheroid-like structure in a 3-dimensional cell culture assay; furthermore, sensitivity of released CTCs to chemotherapeutic agents (sorafenib or oxaliplatin) could be effectively tested utilizing this culture assay. In conclusion, the methodologies presented here offer great promise for accurate enumeration and easy release of captured CTCs, and released CTCs could be cultured for further functional studies.
The prostate-specific antigen (PSA) has been widely used for the early diagnosis of prostate cancer during routine check-ups. However, the low sensitivity of regular PSA tests in the PSA gray zone often means that patients are required to undergo further invasive needle biopsy for the diagnosis of prostate cancer, which may lead to potential overdiagnosis and overtreatment. In this study, a circulating tumor cell (CTC)-chip based on an evaporation-induced reduced graphene oxide (rGO) coating is presented, which enables a highly specific and non-invasive diagnosis of prostate cancer in the PSA gray zone. During the evaporation process of the rGO dispersion, the Marangoni effect induces the self-assembly of a hierarchical micro/nanowrinkled rGO coating, which can capture CTCs after subsequent surface modification of capture agents. Compared to the low diagnostic sensitivity (58.3%) of regular PSA tests, a combination of CTC detection and PSA-based hematological tests via machine-learning analysis can greatly upgrade the diagnostic sensitivity of this disease to 91.7% in clinical trial. Therefore, this study provides a non-invasive alternative with high sensitivity for the diagnosis of prostate cancer in the PSA gray zone.
危险品化学品经营许可证（带存储）