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Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm

Nature Nanotechnology volume 11, pages 936–940 (2016)Cite this article

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Abstract

Deterministic lateral displacement (DLD) pillar arrays are an efficient technology to sort, separate and enrich micrometre-scale particles, which include parasites1, bacteria2, blood cells3 and circulating tumour cells in blood4. However, this technology has not been translated to the true nanoscale, where it could function on biocolloids, such as exosomes. Exosomes, a key target of ‘liquid biopsies’, are secreted by cells and contain nucleic acid and protein information about their originating tissue5. One challenge in the study of exosome biology is to sort exosomes by size and surface markers6,7. We use manufacturable silicon processes to produce nanoscale DLD (nano-DLD) arrays of uniform gap sizes ranging from 25 to 235 nm. We show that at low Péclet (Pe) numbers, at which diffusion and deterministic displacement compete, nano-DLD arrays separate particles between 20 to 110 nm based on size with sharp resolution. Further, we demonstrate the size-based displacement of exosomes, and so open up the potential for on-chip sorting and quantification of these important biocolloids.

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Figure 1: Nano-DLD nanoparticle sorting using pillar array chips with G ranging from 25 to 235 nm and θmax = 5.7°.
Figure 2: Separation of polystyrene beads using a hydrodynamically focused jet in a nano-DLD array.
Figure 3: Experimental demonstration of displacement and fractionation of exosomes in nano-DLD arrays.

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Acknowledgements

We thank M. Pereira for fabrication of the microfluidic cells that hold and interface with nanofluidic chips, S.-C. Kim for the custom Python script to help analyse displacement data, H. Hu for the SEM imaging of exosome samples and P. Meyer for helpful discussion in the preparation of this manuscript. We also thank D. Williams at the Electron Microscopy Resource Laboratory at the University of Pennsylvania for the cryo-EM imaging of exosomes, and the IBM Microelectronics Research Laboratory staff for their contributions to the fabrication of the nano-DLD arrays.

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Author notes

  1. Chao Wang & Yann Astier

    Present address: Present addresses: School of Electrical, Computer and Energy Engineering, and Biodesign Center for Molecular Design & Biomimetics, Arizona State University, Tempe, Arizona 82587, USA (C.W.); Roche Molecular Systems, Pleasanton, California 94588, USA (Y.A.),

  2. Benjamin H. Wunsch and Joshua T. Smith: These authors contributed equally to the paper

Authors and Affiliations

  1. IBM T.J. Watson Research Center, Yorktown Heights, New York 10598, USA

    Benjamin H. Wunsch, Joshua T. Smith, Stacey M. Gifford, Chao Wang, Markus Brink, Robert L. Bruce, Gustavo Stolovitzky & Yann Astier

  2. Department of Physics, Princeton University, Princeton, New Jersey 08540, USA

    Robert H. Austin

  3. Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA

    Gustavo Stolovitzky

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Contributions

Y.A. developed the nano-DLD concept for biocolloids, and led the experimental research. J.T.S. designed and led the chip technology development. M.B. and R.L.B. contributed to the microfabrication process development. B.H.W., J.T.S. and S.M.G. performed the experiments. B.H.W. and S.M.G. analysed the data. B.H.W., Y.A., S.M.G., C.W., R.H.A. and G.S. contributed to the theory and interpretation of the results. G.S. managed the research team. B.H.W. and J.T.S. co-wrote the paper. All the authors contributed to the review of the manuscript.

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Correspondence to Benjamin H. Wunsch, Joshua T. Smith or Gustavo Stolovitzky.

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Wunsch, B., Smith, J., Gifford, S. et al. Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm. Nature Nanotech 11, 936–940 (2016). https://doi.org/10.1038/nnano.2016.134

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