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Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering

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Abstract

Rapid progress in identifying disease biomarkers has increased the importance of creating high-performance detection technologies. Over the last decade, the design of many detection platforms has focused on either the nano or micro length scale. Here, we review recent strategies that combine nano- and microscale materials and devices to produce large improvements in detection sensitivity, speed and accuracy, allowing previously undetectable biomarkers to be identified in clinical samples. Microsensors that incorporate nanoscale features can now rapidly detect disease-related nucleic acids expressed in patient samples. New microdevices that separate large clinical samples into nanocompartments allow precise quantitation of analytes, and microfluidic systems that utilize nanoscale binding events can detect rare cancer cells in the bloodstream more accurately than before. These advances will lead to faster and more reliable clinical diagnostic devices.

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Figure 1: Length scales of interest for biomolecular detection.
Figure 2: The bio-barcode assay combines micro- and nanoparticles for biomolecular detection.
Figure 3: Advances in rapid nucleic acid detection based on micro-to-nanoscale engineering of electrode properties.
Figure 4: Dividing samples into nano- to femtolitre volumes allows highly accurate quantitation of clinically relevant targets.
Figure 5: Microwells separate analytes into femtolitre compartments for quantitative protein detection.
Figure 6: Advanced microdevices for circulating tumour cell isolation.

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Acknowledgements

S.O.K. and E.H.S. acknowledge Genome Canada, the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council, and the Ontario Research Fund for support of their work. M.T. acknowledges the National Institute of Health (NIH) P41 Resource Center, NIH National Institute of Biomedical Imaging and Bioengineering Quantum Grant. R.F.I acknowledges NIH grant R01EB012946 and the Defense Advanced Research Projects Agency (DARPA) Cooperative Agreement HR0011-11-2-0006 for support. D.R.W. acknowledges generous support from DARPA (HR0011-12-2,0001: SUB #5-55065) and a Department of Defense Innovator Award BC100510(W81XWH-11-1-0814). C.A.M. acknowledges support from the Center for Cancer Nanotechnology Excellence (CCNE) initiative of the National Institutes of Health (NIH), the Nanoscale Science and Engineering Centers (NSEC) initiative of the National Science Foundation, the Prostate Cancer Foundation, National Institute of Arthritis and Musculosketal and Skin Diseases/NIH, and DARPA.

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Correspondence to Shana O. Kelley.

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R.F.I. is a scientific founder, a Director, and has equity in SlipChip. D.R.W. is a scientific founder, a Director, and has equity in Quanterix. S.O.K. is a founder, a Director, and has equity in Xagenic. E.H.S. holds equity in Xagenic.

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Kelley, S., Mirkin, C., Walt, D. et al. Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering. Nature Nanotech 9, 969–980 (2014). https://doi.org/10.1038/nnano.2014.261

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