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Here, we demonstrate nanoparticle\u2010based 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\u2010free DNA nanoparticles and EVs followed by on\u2010chip biomarker fluorescent staining for DNA and Glypican\u20101. Using a blinded cohort, these biomarkers differentiated pancreatic cancer from benign pancreatic diseases, including cysts, pancreatitis, and precancerous low\u2010grade 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\u2010guided 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\u2010stage pancreatic cancer and high\u2010grade in situ precancerous lesions. This DEP\u2010based technique shows that multiple types of cancer\u2010derived nanoparticles can be quickly and easily recovered from plasma making it promising for future clinical diagnostics.<\/jats:p>","DOI":"10.1002\/smll.202502532","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T07:37:43Z","timestamp":1775633863000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liquid Biopsy Differentiation of Pancreatic Cancer From Non\u2010Cancerous Pancreatic Disease Using Dielectrophoresis\u2010Recovered Nanoparticles Carrying Cell\u2010Free DNA and Protein Biomarkers"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-570X","authenticated-orcid":false,"given":"Anna","family":"Malakian","sequence":"first","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusta","family":"Modestino","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Bueno","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Machireddy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering School of Medicine Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5530-5843","authenticated-orcid":false,"given":"Jason","family":"Ware","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"},{"name":"Department of Biomedical Engineering School of Medicine Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6740-290X","authenticated-orcid":false,"given":"Sean","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"},{"name":"Department of Biomedical Engineering School of Medicine Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3159-2585","authenticated-orcid":false,"given":"Ella","family":"Stimson","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"},{"name":"Department of Biomedical Engineering School of Medicine Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3110-768X","authenticated-orcid":false,"given":"Sarah","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"},{"name":"Department of Biomedical Engineering School of Medicine Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-1615","authenticated-orcid":false,"given":"Joshua C.","family":"Saldivar","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"},{"name":"Division of Oncological Sciences Knight Cancer Institute Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4154-6002","authenticated-orcid":false,"given":"Ashley R.","family":"Woodfin","sequence":"additional","affiliation":[{"name":"RyboDyn Inc.  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