An integrated microfluidic system for cholangiocarcinoma diagnosis from bile by using specific affinity probes

Cancer can destroy human lives, pose significant financial burdens, and be difficult to diagnose in its early stages. For instance, the conventional antibody-body tests, such as carbohydrate antigen 19-9 (CA19-9) and carci-noembryonic antigen (CEA) which have been routinely used in laboratory tests, are not specific enough for bile duct cholangiocarcinoma (CCA), meaning that it typically remains undiagnosed until advanced stages. Thus, we aim to develop an automated integrated microfluidic system to facilitate the process of CCA diagnosis. In this system, tumor cells were automatically detected in small volume of CCA patient bile (3 mL) via three CCA-specific affinity reagents, including an antibody, an aptamer, and a glycosaminoglycan, which were mobilized on magnetic beads. This integrated microfluidic system automated the entire procedure involved bile centrifu-gation and CCA capture/staining in only 80 min (20, 30, & 30 min for sample treatment, cell capture, & im-munostaining, respectively). Single-blind tests of clinical samples from CCA patients and non-CCA individuals with all three affinity reagents were conducted. Three out of three positive and four out of four negative samples were tested accurately, as determined through use of CCA and non-CCA patient samples. This integrated microfluidic system may therefore serve as a promising tool for improving detection of CCA.

Automated summary

Cancer can have devastating consequences and is often difficult to detect in its early stages. A new automated integrated microfluidic system has been developed to improve the diagnosis of bile duct cholangiocarcinoma (CCA), a type of cancer that is challenging to diagnose. This system uses three CCA-specific affinity reagents to detect tumor cells in a small sample of CCA patient bile and can automate the entire detection process in just 80 minutes.