ICP-MS and Photothermal Dual-Readout Assay for Ultrasensitive and Point-of-Care Detection of Pancreatic Cancer Exosomes.

ABSTRACT

Pancreatic cancer is known to have a high mortality rate, and its early diagnosis remains challenging due to the occult location of the pancreas. Exosomes derived from pancreatic cancer cells specifically express glypican-1, which may provide a liquid biopsy opportunity for the early diagnosis of pancreatic cancer. Herein, an inductively coupled plasma mass spectrometry (ICP-MS) and photothermal dual-readout platform was proposed for the ultrasensitive and point-of-care analysis of pancreatic cancer exosomes. In our design, exosomes were specifically captured by the sandwich immunoassay, and simultaneously, alkaline phosphatase was introduced in a low-background manner. The alkaline phosphatase triggered the hydrolysis of l-ascorbic acid 2-phosphate to produce ascorbic acid, followed by the etching of Fe3O4@MnO2 nanoflowers. As a result, the Mn2+ generated by etching stripped off the Fe3O4 and was quantified using ICP-MS. Meanwhile, the reduced Fe3O4@MnO2 was applied for the photothermal assay by oxidizing dopamine with MnO2. The protocol exhibits a detection limit down to 19.1 particles mL-1, which is the most sensitive protocol reported so far. To our knowledge, this is the first endeavor for exosome quantification using ICP-MS and photothermal methods. The developed dual-readout platform not only is capable of distinguishing pancreatic cancer patients from healthy people, but also shows excellent discernibility of individual differences at low concentrations of exosomes. This dual-readout assay is a promising platform for the ultrasensitive and point-of-care detection of exosomes in liquid biopsy-based early cancer diagnosis.