Nanoscale lateral displacement arrays for the separation of exosomes

Deterministic lateral displacement (DLD) pillar arrays are an efficient technology to sort, separate and enrich micrometre-scale particles, which include parasites, bacteria, blood cells and circulating tumour cells in blood. 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 tissue. One challenge in the study of exosome biology is to sort exosomes by size and surface markers.

Researchers at IBM’s T.J. Watson Research Center use manufacturable silicon processes to produce nanoscale DLD (nano-DLD) arrays of uniform gap sizes ranging from 25 to 235 nm. They 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, the researchers demonstrate the size-based displacement of exosomes, and so open up the potential for on-chip sorting and quantification of these important biocolloids.

Nano-DLD nanoparticle sorting using pillar array chips
with G ranging from 25 to 235 nm and θmax = 5.7°


a, Schematic representation of a pillar array that illustrates the array parameters of maximum angle, θmax, pillar gap size, G, pillar pitch, λ, and row-to-row shift, δ. Trajectories for particles with diameter DP, below the nominal critical diameter, DC, follow a laminar flow in a zigzag mode (red), whereas larger colloids with DP ≥ DC follow θmax in a bumping mode (blue). b, Scanning electron microscope image of a sorting array with λ = 400 nm and G = 25 nm. c, Optical microscope image (left column) of a typical full-width injection nano-DLD device that shows the overall configuration of the array. The blue triangle shows the area that should fluoresce if all the fluorescent particles traversed the array in the bumping mode. Scale bar, 20 µm. The second column shows SEM images of the inlet and outlet regions that border the nano-DLD array. Scale bar, 10 µm. The three fluorescence microscopy images of dyed polystyrene beads that flow into the inlet region (top row) and exit the array outlet region (bottom row) correspond to those shown in the SEM images. The lateral displacement modes for zigzag, partial and bumping are shown for DP = 20 nm/G = 214 nm, DP = 50 nm/G = 134 nm and DP = 110 nm/G = 235 nm, respectively. The migration angle, θ, indicates the lateral displacement of the particle flux in the array.

Wunsch BH, Smith JT, Gifford SM, Wang C, Brink M, Bruce RL, Austin RH, Stolovitzky G, Astier Y. (2016) Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm. Nat Nanotechnol [Epub ahead of print]. [abstract]

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