Matrix-insensitive protein assays push the limits of biosensors in medicine


Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse clinical samples (for example, serum, urine, cell lysates or saliva) with high sensitivity and large linear dynamic range. A major limitation confounding other technologies is signal distortion that occurs in various matrices due to heterogeneity in ionic strength, pH, temperature and autofluorescence. Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our magnetic nanosensor technology can be directly applied to a variety of settings such as molecular biology, clinical diagnostics and biodefense.

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Figure 1: Sensor architecture and assay.
Figure 2: Sensitivity and linear dynamic range (on a log-log plot) of magneto-nanosensors and ELISA.
Figure 3: Magnetonanosensors exhibit matrix-insensitive detection.
Figure 4: Multiplex protein detection in a diversity of media.
Figure 5: Femtomolar-level multiplex tumor marker profiling in xenograft mice.


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This work was supported in part by US National Cancer Institute grants 1U54CA119367 and N44CM–2009-00011, US National Science Foundation grant ECCS-0801385-000, US Defense Threat Reduction Agency grant HDTRA1-07-1-0030-P00005, the US Defense Advanced Research Projects Agency/Navy Grant N00014–02-1–0807, NCI ICMIC P50 CA114747, the US Department of Veterans Affairs Merit Review B4872, the Canary Foundation and The National Semiconductor Corporation. R.S.G. acknowledges financial support from Stanford Medical School Medical Scientist Training Program and a National Science Foundation graduate research fellowship. C.H.N. acknowledges financial support from the Denmark-American Foundation and the Lundbeck Foundation.

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R.S.G., D.A.H., S.S.G. and S.X.W designed research; R.S.G., D.A.H., C.H.N. and K.E.M. performed research; R.S.G., D.A.H., C.H.N., S.J.O., H.Y., K.E.M., R.J.W., B.M., J.C.L., S.S.G. and S.X.W contributed new reagents and/or analytical tools; R.S.G., D.A.H. and S.X.W analyzed data; S.J.O. and S.X.W. designed the magnetic sensors; R.S.G. and H.Y. developed the biochemistry; and R.S.G., S.S.G. and S.X.W. wrote the paper.

Corresponding authors

Correspondence to Sanjiv S Gambhir or Shan X Wang.

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Competing interests

Stanford University has licensed part of the magnetic bioassay chip technology contained in this publication to MagArray Inc., an early-stage startup company in Silicon Valley, California. S.X.W., S.S.G., H.Y. and S.J.O. hold financial interests in MagArray in the form of stock options.

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Gaster, R., Hall, D., Nielsen, C. et al. Matrix-insensitive protein assays push the limits of biosensors in medicine. Nat Med 15, 1327–1332 (2009).

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