Liquid Biopsy Differentiation of Pancreatic Cancer From Non‐Cancerous Pancreatic Disease Using Dielectrophoresis‐Recovered Nanoparticles Carrying Cell‐Free DNA and Protein Biomarkers

ABSTRACT Cancer‐derived extracellular vesicle (EV) nanoparticles carry important biomarkers but are difficult to recover from plasma, making EV‐based diagnostics a challenge for clinical settings. Here, we demonstrate nanoparticle‐based detection of pancreatic cancer using dielectrophoresis (DEP) nanoparticle recovery technology, which purifies nanoparticles from undiluted plasma and quantifies associated biomarkers. We combined both nanoparticle recovery and biomarker quantification on a single device by simultaneously collecting cell‐free DNA nanoparticles and EVs followed by on‐chip biomarker fluorescent staining for DNA and Glypican‐1. Using a blinded cohort, these biomarkers differentiated pancreatic cancer from benign pancreatic diseases, including cysts, pancreatitis, and precancerous low‐grade intraductal papillary mucinous neoplasm (IPMN) lesions, with a sensitivity of 0.92, a specificity of 0.83, and an AUC of 0.93. The AUC increased to 0.97 for patients over 50 years old. This is higher than the standard invasive endoscopic ultrasound‐guided fine needle aspiration tissue biopsy procedure (AUC 0.79). This study is among the first demonstrating a combined threshold of DNA and protein levels that can distinguish pancreatic cancer from its precursor IPMN lesions. We also demonstrated the detection of early‐stage pancreatic cancer and high‐grade in situ precancerous lesions. This DEP‐based technique shows that multiple types of cancer‐derived nanoparticles can be quickly and easily recovered from plasma making it promising for future clinical diagnostics.