Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a relatively low incidence but a high mortality rate, primarily due to difficulties in early detection. Current state-of-the-art methods for diagnosing early-stage PDAC tend to be invasive, time-consuming, and unreliable, primarily due to the difficulties associated with the early detection of pancreatic cancers. Here we show a quick and sensitive method for the early diagnosis of PDAC using a signal-enhanced lateral flow immunoassay called SELFI. We develop SELFI, which generates a strong colorimetric signal through multiple hotspots formed by plasmonic gold nanoparticles (AuNPs) assembled on a silica nanoparticle. Our SELFI assay achieves a 10,123-fold increase in the limit of detection compared to conventional lateral flow immunoassays using 20 nm AuNPs, providing results within 15 min. We demonstrate that SELFI enables early diagnosis of PDAC, as indicated by a receiver operating characteristic curve and a larger area under the curve compared to the enzyme-linked immunosorbent assay. SELFI’s effective diagnostic features can enhance the timely identification of PDAC and may also serve in the early diagnosis of a range of other diseases.
Data availability
The processed quantitative data generated in this study, including assay readouts and data used for statistical and ROC analyses, are provided in the Supplementary Tables associated with this paper. Individual-level clinical data derived from human serum samples are not publicly available due to ethical and legal restrictions related to participant privacy and the terms of informed consent. These data are stored in controlled-access repositories at the Human Bioresource Center of Seoul National University Bundang Hospital. Access to the restricted clinical data may be granted to qualified researchers for non-commercial research purposes, subject to approval by the Human Bioresource Center and the relevant Institutional Review Board. Requests for access should be directed to the corresponding author (Jong-chan Lee; ljc0316@snubh.org), who will coordinate the application process. A response to access requests is typically provided within 2–4 weeks. Data will remain available for the duration permitted by institutional and ethical regulations. Source data for all figures are provided with this paper. Source data are provided with this paper.
Code availability
The code used in this study is available at GitHub (https://github.com/JKim-45/SELFI) and has been archived on Zenodo with a https://doi.org/10.5281/zenodo.17958691.
References
Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin. 73, 17–48 (2023).
Mizrahi, J. D., Surana, R., Valle, J. W. & Shroff, R. T. Pancreatic cancer. Lancet 395, 2008–2020 (2020).
Rawla, P., Sunkara, T. & Gaduputi, V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J. Oncol. 10, 10–27 (2019).
Rahib, L. et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913–2921 (2014).
Kleeff, J. et al. Pancreatic cancer. Nat. Rev. Dis. Primers 2, 16022 (2016).
Eissa, M. A. L. et al. Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood. Clin. Epigenetics 11, 59 (2019).
Kobi, M. et al. Imaging and management of pancreatic cancer. Semin. Ultrasound CT MR 41, 139–151 (2020).
Locker, G. Y. et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J. Clin. Oncol. 24, 5313–5327 (2006).
Ballehaninna, U. K. & Chamberlain, R. S. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J. Gastrointest. Oncol. 3, 105–119 (2012).
McGuigan, A. et al. Pancreatic cancer: a review of clinical diagnosis, epidemiology, treatment and outcomes. World J. Gastroenterol. 24, 4846–4861 (2018).
Blackford, A. L. et al. Pancreatic cancer surveillance and survival of high-risk individuals. JAMA Oncol. 10, 1087–1096 (2024).
Cohen, J. D. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359, 926–930 (2018).
Pereira, S. P. et al. Early detection of pancreatic cancer. Lancet Gastroenterol. Hepatol. 5, 698–710 (2020).
Su, C.-W., Tian, J.-H., Ye, J.-J., Chang, H.-W. & Tsai, Y.-C. Construction of a label-free electrochemical immunosensor based on Zn-Co-S/graphene nanocomposites for carbohydrate antigen 19-9 detection. Nanomaterials 11, 1475 (2021).
Wu, S. et al. Collard-like Bi2S3@ Au nanocomposites-based label free electrochemical immunosensor for quantitative detection of CA19-9. Talanta 285, 127299 (2025).
Zhao, T. & Jin, B. A label-free electrochemical biosensor based on a bimetallic organic framework for the detection of carbohydrate antigen 19-9. Anal. Methods 16, 6173–6182 (2024).
Han, X., Lin, S., Li, Y., Cheng, C. & Han, X. Near-infrared photothermal immunoassay for pancreatic cancer biomarker CA 19-9 on a digital thermometer. Anal. Chim. Acta 1098, 117–124 (2020).
Xia, J., Li, Y., Xin, Y., Kang, L. & Lu, D. Early detection for carbohydrate antigen-19-9 based on surface enhanced Raman spectroscopy aptamer sensor. Microchem. J. 207, 111750 (2024).
Hwang, I.-J. et al. Confined growth of Ag nanogap shells emitting stable Raman label signals for SERS liquid biopsy of pancreatic cancer. Biosens. Bioelectron. 248, 115948 (2024).
Di Nardo, F., Chiarello, M., Cavalera, S., Baggiani, C. & Anfossi, L. Ten years of lateral flow immunoassay technique applications: trends, challenges and future perspectives. Sensors 21, 5185 (2021).
Wang, Z. et al. An overview for the nanoparticles-based quantitative lateral flow assay. Small Methods 6, 2101143 (2022).
Wang, J. et al. Hollow Au-Ag nanoparticles labeled immunochromatography strip for highly sensitive detection of clenbuterol. Sci. Rep. 7, 41419 (2017).
Wei, Z., Xi, Z., Vlasov, S., Ayala, J. & Xia, X. Nanocrystals of platinum-group metals as peroxidase mimics for in vitro diagnostics. Chem. Commun. 56, 14962–14975 (2020).
Wei, Z., Luciano, K. & Xia, X. Catalytic gold-iridium nanoparticles as labels for sensitive colorimetric lateral flow assay. ACS Nano 16, 21609–21617 (2022).
Kim, H.-M. et al. Au–Ag assembled on silica nanoprobes for visual semiquantitative detection of prostate-specific antigen. J. Nanobiotechnol. 19, 73 (2021).
Hong, D., Jo, E.-J., Jung, C. & Kim, M.-G. Absorption-modulated SiO2@Au core–satellite nanoparticles for highly sensitive detection of SARS-CoV-2 nucleocapsid protein in lateral flow immunosensors. ACS Appl. Mater. Interfaces 14, 45189–45200 (2022).
Kim, H.-M. et al. Multi-quantum dots-embedded silica-encapsulated nanoparticle-based lateral flow assay for highly sensitive exosome detection. Nanomaterials 11, 768 (2021).
Bock, S. et al. Lateral flow immunoassay with quantum-dot-embedded silica nanoparticles for prostate-specific antigen detection. Nanomaterials 12, 33 (2022).
Khelifa, L., Hu, Y., Jiang, N. & Yetisen, A. K. Lateral flow assays for hormone detection. Lab Chip 22, 2451–2475 (2022).
Mahmoudi, T., Shirdel, B., Mansoori, B. & Baradaran, B. Dual sensitivity enhancement in gold nanoparticle-based lateral flow immunoassay for visual detection of carcinoembryonic antigen. Anal. Sci. Adv. 1, 161–172 (2020).
Zhu, J. et al. One-pot synthesized Au@Pt nanostars-based lateral flow immunoassay for colorimetric and photothermal dual-mode detection of SARS-CoV-2 nucleocapsid antibody. Anal. Chim. Acta 1292, 342241 (2024).
Huang, Y. et al. Lateral flow assay for carbohydrate antigen 19–9 in whole blood by using magnetized carbon nanotubes. Microchim. Acta 184, 4287–4294 (2017).
Jiao, X. et al. Lateral flow immunoassay based on time-resolved fluorescence microspheres for rapid and quantitative screening CA199 in human serum. Int. J. Mol. Sci. 23, 9991 (2022).
Shin, M. et al. Highly sensitive multiplexed colorimetric lateral flow immunoassay by plasmon-controlled metal–silica isoform nanocomposites: PINs. Nano Converg. 11, 42 (2024).
Jain, P. K. & El-Sayed, M. A. Plasmonic coupling in noble metal nanostructures. Chem. Phys. Lett. 487, 153–164 (2010).
Zuo, Z. et al. Multiple plasmon couplings in 3D hybrid Au-nanoparticles-decorated Ag nanocone arrays boosting highly sensitive surface enhanced Raman scattering. Nano Res. 15, 317–325 (2022).
Su, D. et al. Ordered gold nanocluster-based plasmonic hotspot arrays for SERS detection of single molecules. ACS Appl. Nano Mater. 5, 17067–17077 (2022).
Li, H., Merkl, P., Sommertune, J., Thersleff, T. & Sotiriou, G. A. SERS hotspot engineering by aerosol self-assembly of plasmonic Ag nanoaggregates with tunable interparticle distance. Adv. Sci. 9, 2201133 (2022).
Li, X. et al. Au Multimer@MoS2 hybrid structures for efficient photocatalytical hydrogen production via strongly plasmonic coupling effect. Nano Energy 30, 549–558 (2016).
Yu, G. et al. Collective excitation of plasmon-coupled Au-nanochain boosts photocatalytic hydrogen evolution of semiconductor. Nat. Commun. 10, 4912 (2019).
Ma, L. et al. Multi-interfacial plasmon coupling in multigap (Au/AgAu)@ CdS core–shell hybrids for efficient photocatalytic hydrogen generation. Nanoscale 12, 4383–4392 (2020).
Choi, I. et al. Colorimetric tracking of protein structural evolution based on the distance-dependent light scattering of embedded gold nanoparticles. Chem. Commun. 48, 2286–2288 (2012).
An, H. J. et al. High-spatial and colourimetric imaging of histone modifications in single senescent cells using plasmonic nanoprobes. Nat. Commun. 12, 5899 (2021).
Liu, D. et al. Ultrasensitive and stable Au dimer-based colorimetric sensors using the dynamically tunable gap-dependent plasmonic coupling optical properties. Adv. Funct. Mater. 28, 1707392 (2018).
Materón, E. M. et al. Colorimetric detection of SARS-CoV-2 using plasmonic biosensors and smartphones. ACS Appl. Mater. Interfaces 14, 54527–54538 (2022).
Kang, H. et al. Near-infrared SERS nanoprobes with plasmonic Au/Ag hollow-shell assemblies for in vivo multiplex detection. Adv. Funct. Mater. 23, 3719–3727 (2013).
Choe, A. et al. Stretchable and wearable colorimetric patches based on thermoresponsive plasmonic microgels embedded in a hydrogel film. NPG Asia Mater. 10, 912–922 (2018).
Sun, Z., Du, J., Duan, F., He, K. & Jing, C. Simulation and synthesis of Fe3O4–Au satellite nanostructures for optimised surface-enhanced Raman scattering. J. Mater. Chem. C 6, 2252–2257 (2018).
De Silva Indrasekara, A. S. et al. Tailoring the core–satellite nanoassembly architectures by tuning internanoparticle electrostatic interactions. Langmuir 34, 14617–14623 (2018).
Song, D. & Jing, D. Insight into the localized surface plasmon resonance property of core-satellite nanostructures: theoretical prediction and experimental validation. J. Colloid Interface Sci. 505, 373–382 (2017).
Wang, Y. et al. Establishment of time-resolved fluorescence immunochromatographic assay for detection of carbohydrate antigen 19-9. Sheng Wu Gong Cheng Xue Bao 34, 1012–1018 (2018).
Stöber, W., Fink, A. & Bohn, E. Controlled growth of monodisperse silica spheres in the micron size range. J. Colloid Interface Sci. 26, 62–69 (1968).
Zhang, J. H., Zhan, P., Wang, Z. L., Zhang, W. Y. & Ming, N. B. Preparation of monodisperse silica particles with controllable size and shape. J. Mater. Res. 18, 649–653 (2003).
Li, H. et al. Functionalized silica nanoparticles: classification, synthetic approaches and recent advances in adsorption applications. Nanoscale 13, 15998–16016 (2021).
Ruan, Q., Shao, L., Shu, Y., Wang, J. & Wu, H. Growth of monodisperse gold nanospheres with diameters from 20 nm to 220 nm and their core/satellite nanostructures. Adv. Opt. Mater. 2, 65–73 (2014).
Tempero, M. A. et al. Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer. Cancer Res. 47, 5501–5503 (1987).
Robin, X. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform. 12, 77 (2011).
Werner, W. S. M., Glantschnig, K. & Ambrosch-Draxl, C. Optical constants and inelastic electrons scattering data for 17 elemental metals. J. Phys. Chem. Ref. Data 38, 1013–1092 (2009).
Martin, M. N., Basham, J. I., Chando, P. & Eah, S.-K. Charged gold nanoparticles in non-polar solvents: 10-min synthesis and 2D self-assembly. Langmuir 26, 7410–7417 (2010).
Parolo, C. et al. Tutorial: design and fabrication of nanoparticle-based lateral-flow immunoassays. Nat. Protoc. 15, 3788–3816 (2020).
Torchiano, M. effsize: Efficient Effect Size Computation (R package version 0.8.1). CRAN, https://CRAN.R-project.org/package=effsize (2020).
Champely, S., Ekstrom, C., Dalgaard, P., Gill, J., Weibelzahl, S. & Anandkumar, A. pwr: Basic Functions for Power Analysis. R package version 1.3-0. https://CRAN.R-project.org/package=pwr (2018).
Acknowledgements
This study was funded by the Ministry of Science and ICT (NRF-2022R1A2C2012883; B.-H.J.), the Bio and Medical Technology Development Program (2021M3C1C3097211; B.-H.J.), the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (RS-2023-00222910; J.-C.L. and B.-H.J., RS-2025-00558156; J.S.), and the National Institutes of Health (NIH) (R01DK133864; L.P.L.).
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S.J., M.S., J.K., and B.-H.J. conceived and designed the experiments. S.J., M.S., J.H., H.-J.B., Y.Y., H.-S.C., K.Y., J.-S.C., J.A., G.A., and J.K. conducted experiments and analyses. J.K. developed custom R scripts for statistical analysis. S.J., M.S., J.H., Y.Y., J.K., J.-C.L., and B.-H.J. wrote the manuscript. S.J., M.S., J.H., H.C., J.-H.H., J.K., J.S., J.-C.L., L.P.L., and B.-H.J. revised the manuscript. L.P.L. and B.-H.J. supervised the overall process. All authors approved the final version of the manuscript. S.J., M.S., and J.H. contributed equally.
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Jang, S., Shin, M., Han, J. et al. Early diagnosis of pancreatic ductal adenocarcinoma by signal-enhanced lateral flow immunoassay: SELFI. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69204-7
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DOI: https://doi.org/10.1038/s41467-026-69204-7