A high throughput blood-based assay for the early detection of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due in part to the cancer being diagnosed is at a late stage when effective treatment options are limited. Early detection of PDAC via liquid biopsy would revolutionize survival from the disease. To address the lack of effective non-invasive detection assays for PDAC, we developed a protease activity-based assay using a magnetic nanosensor (PAC-MANN). The PAC-MANN assay leverages protease activity in blood to amplify the signal of the target-probe based sensor. An initial screening revealed that the PAC-MANN assay could reliably differentiate patients with PDAC from healthy subjects and patients at high risk of PDAC. Finally, in two cohorts: training (n=145) and blinded validation (n=72), we demonstrated that the PAC-MANN assay had high specificity (86%) and sensitivity (78%) for detection of PDAC compared to healthy subjects. This performance was enhanced when combined with the current standard of care assay, CA19-9 (100% specificity, 84% sensitivity). Our results demonstrate a novel assay that is rapid, high-throughput, and requires low specimen volume, which may not only improve cancer detection but could be useful for monitoring of at-risk patients and could be deployed in low resource settings. ### Competing Interest Statement UD is a founder of and has an equity interest in: (i) DxNow Inc., a company that is developing microfluidic IVF tools and imaging technologies, (ii) Koek Biotech, a company that is developing microfluidic technologies for clinical solutions, (iii) Levitas Inc., a company focusing on developing microfluidic sorters using magnetic levitation, (iv) Hillel Inc., and Hillal Biotech, companies bringing microfluidic cell phone tools for spermograms to home settings, and (v) Mercury Biosciences, a company developing extracellular vesicle isolation technologies. UD's interests were viewed and managed in accordance with the conflict-of-interest policies. JLMM and JMF have a patent pending for the PAC-MANN assay. The other authors have no conflict of interest. ### Funding Statement This work was funded by CEDAR grant number Full7200120, ManscriptPrep2022-1639, Full2023-1733 (JMF) and by National Cancer Institute grant number P30CA069533 (MHW, JMF). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: We have applied with all ethical guidelines for human research participants. The Institutional Review Board at Oregon Health and Science University provided guidelines for study procedures and protocol was approved (IRB00005169). Informed consent was obtained from all study participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors