A novel nanoplasmonic sensing technology can better detect cholangiocarcinoma (CCA) and aid in the early diagnosis of the disease, according to a new study published in Advanced Science

Effective diagnostic methods that can detect CCA early are lacking, which leads to high mortality rates due to the disease often being identified when it is no longer resectable. 

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In the present study, a team of researchers led by Hyungsoon Im, PhD, from Massachusetts General Hospital in Boston reported a new technology called fluorescence-amplified extracellular vesicle sensing technology (FLEX) that could analyze single tumor-derived extracellular vesicles with high sensitivity.

According to the authors, FLEX is able to identify widely heterogeneous tumor-derived extracellular vesicles and their marker levels. It is also able to identify small tumor-derived extracellular vesicles that conventional methods cannot detect.

Using this new method, the researchers detected tumor-derived extracellular vesicles in clinical bile samples using the tumor markers MUC1, EGFR, and EPCAM, which are identified in CCA. 

“The FLEX assay detected CCA with an area under the curve of 0.93,” the researchers reported, which is “significantly better than current clinical markers.”

The FLEX assay captures extracellular vesicles on a plasmonic gold nanowell surface. These extracellular vesicles are then immunolabeled for biomarkers associated with cancer to identify tumor-derived vesicles. The fluorescence signals from the extracellular vesicles are amplified by the underlying plasmonic gold nanowell structures, which create sufficient signals to identify single vesicles.

CCA is a heterogeneous group of rare malignant tumors originating from cells of the biliary tree. The disease is responsible for around 15% of all primary liver tumors and is the second most common primary liver malignancy after hepatocellular carcinoma. The incidence of the disease has been increasing in recent years.


Jeong MH, Son T, Tae YK, et al. Plasmon-enhanced single extracellular vesicle analysis for cholangiocarcinoma diagnosis. Adv Sci (Weinh). Published online January 25, 2023. doi:10.1002/advs.202205148