Label-free biomarker detection from whole blood

Abstract

Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive1,2,3,4,5,6,7,8,9,10,11,12,13. However, detecting these biomarkers in physiological fluid samples is difficult because of problems such as biofouling and non-specific binding, and the resulting need to use purified buffers greatly reduces the clinical relevance of these sensors. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. A microfluidic purification chip simultaneously captures multiple biomarkers from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 µl sample of whole blood in less than 20 min. This study marks the first use of label-free nanosensors with physiological solutions, positioning this technology for rapid translation to clinical settings.

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Figure 1: Schematic of MPC operation.
Figure 2: MPC operation.
Figure 3: Nanosensor electrical characteristics.
Figure 4: Label-free sensing.

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Acknowledgements

The authors would like to thank J. Straight for many helpful discussions, M. Look and J. Bertram for blood samples, M. Power for device processing assistance, M. Saltzman for departmental support, and D. Stern and K. Milnamow for critical reading of the manuscript. The work was supported in part by the National Institute of Health (NIH) through grant no. R01EB008260 (M.A.R. and T.M.F.), Canadian Institute for Advanced Research (CIfAR), and Army Research Office (ARO) (W911NF-08-1-0365). This work was performed in part at the Cornell Nanoscale Science and Technology Facility, a member of the National Nanotechnology Infrastructure Network that is supported by the National Science Foundation (NSF), and at the Yale Institute for Nanoscience and Quantum Engineering. This paper is dedicated to the memory of Alan R. Stern.

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Contributions

E.S. designed the MPC and performed all MPC experiments. E.S. and B.R.I. designed the MPC fabrication and performed MPC processing. E.S., A.V. and M.A.R. designed the nanosensor fabrication process and E.S., A.V. and B.R.I. performed nanosensor processing. D.J.M. assisted with MPC and nanosensor experimental design, and data analysis. E.S., A.V., N.K.R. and J.M.C. performed the sensing measurements. E.S., J.M.C. and J.P. prepared and analysed the protein samples. E.S., M.A.R. and T.M.F. wrote the manuscript and edited it, with contributions from all authors.

Corresponding authors

Correspondence to Mark A. Reed or Tarek M. Fahmy.

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Stern, E., Vacic, A., Rajan, N. et al. Label-free biomarker detection from whole blood. Nature Nanotech 5, 138–142 (2010). https://doi.org/10.1038/nnano.2009.353

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