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A plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disease, whereas type 2 diabetes (T2D) results from insulin resistance and beta cell dysfunction. Previously, the onset of these two separate diseases was easily distinguished, with children being most at risk for T1D and T2D occurring in overweight adults. However, the dramatic rise in obesity, coupled with the notable increase in T1D, has created a large overlap in these previously discrete patient populations. Delayed diagnosis of T1D can result in severe illness or death, and rapid diagnosis of T1D is critical for the efficacy of emerging therapies. However, attempts to apply next-generation platforms have been unsuccessful for detecting diabetes biomarkers. Here we describe the development of a plasmonic gold chip for near-infrared fluorescence–enhanced (NIR-FE) detection of islet cell–targeting autoantibodies. We demonstrate that this platform has high sensitivity and specificity for the diagnosis of T1D and can be used to discover previously unknown biomarkers of T1D.

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Figure 1: Greater signal detection on plasmonic gold surface compared with standard surfaces.
Figure 2: The plasmonic chip readily differentiates T1D and T2D in ultralow serum or blood samples.
Figure 3: Scatter plot for diabetes autoantibodies.
Figure 4: The plasmonic chip permits differentiation of immunoglobulin isotypes from a single ultralow volume sample.

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Acknowledgements

We thank the patient volunteers. We thank P.J. Utz and D. Wilson for helpful discussions. We thank M. Gong, J. Wu and L. Zhang for help with experiments; we thank C. Yan for help with the scatter plot for diabetes autoantibodies. This work was supported by grants from the Stanford C-IDEA program (US National Institutes of Health grant 1 RC4 TW008781-01), the US National Institutes of Health DP2OD006740 (to B.J.F.) and the Juvenile Diabetes Research Foundation 17-2013-528 (to B.J.F.) and the National Cancer Institute of the US National Institutes of Health (5R01CA135109-02) and the Stanford SPARK program (to H.D.). B.Z. acknowledges support from the Stanford Bio-X SIGF fellowship. R.B.K. received unrestricted fellowship support from Genentech and the Child Health Research Institute at Stanford. B.J.F. is a Bechtel Endowed Faculty Scholar.

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Authors

Contributions

B.J.F. conceived of the study. B.Z., R.B.K., H.D. and B.J.F. designed the experiments, analyzed the data and wrote the manuscript. B.Z. and R.B.K. conducted the experiments.

Corresponding authors

Correspondence to Hongjie Dai or Brian J Feldman.

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Competing interests

Stanford University and the authors have filed patents for both the technology and the use of the technology to detect islet cell–targeting autoantibodies with the US Patent and Trademark Office and via the Patent Cooperation Treaty.

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Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Tables 1–3, and Supplementary Methods (PDF 1222 kb)

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Zhang, B., Kumar, R., Dai, H. et al. A plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes. Nat Med 20, 948–953 (2014). https://doi.org/10.1038/nm.3619

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