Platform of single-molecule enzyme activity-based liquid biopsy for detection of pancreatic adenocarcinoma at early stages

ABSTRACT Liquid biopsy analyzes biomolecules in biofluids to provide critical information for the early detection of diseases and the development of more effective treatment strategies. Among these biomolecules, the functional states of proteins offer particularly valuable insights due to their direct correlation with phenotypic changes. However, current approaches for assessing protein function in liquid biopsies are often limited by low detection sensitivity. Here, we present a liquid biopsy platform that analyzes single-molecule protease/peptidase activity to detect pathological alterations in enzyme function in blood samples. The platform demonstrates potential for identifying patients with early-stage (stage I-II) pancreatic ductal adenocarcinoma (PDAC). Competing Interest Statement S. S. and Y. K. are cofounders, employees and shareholders of Cosomil, Inc. H. H., M. M., M. S., and N. I. are employees of Cosomil, Inc. T. M., K. H., R. W., and T. K. are advisors and shareholders of Cosomil, Inc. S. S., Y. K., R. W., Y. U., and T. K. are inventors of a patent describing the design strategies of fluorogenic probes for proteases/peptidases.