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

Abstract

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. 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.

Broken flow symmetry explains the dynamics of small particles in deterministic lateral displacement arrays

“…These experiments used full-width injection, in which particles are introduced across the entire width of the array inlet, and the migration angle is measured based on how much the particle flux is deflected (11). Beads were run at velocities > 5 mm/s (toward the maximum obtainable with our experimental setup) to reduce the influence of diffusion (Pe ∼200).…”

“…In other words, particles in DLD arrays would exhibit two types of trajectories: zigzag or bumping mode. However, several DLD experiments (2,11,15) have shown trajectories that deviate from the original theory in that particles migrated laterally in the array with angles that were neither zero (zigzag mode) nor θp (bumping mode).…”

“…Since their introduction (2), DLD pillar arrays have been used in applications from cell sorting (3) to biosensors (4) and can efficiently sort, separate, and enrich a broad range of particles, including parasites (5), bacteria (6), blood cells (7)(8)(9), circulating tumor cells (10), and exosomes (11). The original theory (12) predicts that particle trajectories fall into one of two modes, bumping or zigzag, as determined by the critical diameter Dc defined by the array geometry (2,12).…”

Microfluidics‐based on‐a‐chip systems for isolating and analysing extracellular vesicles

“…As a result, 51–1500 nm particles were successfully separated by a large-pore DLD device (with 2 μ m gaps between pillars) [94]. The true nano-DLD system was first constructed by Wunsch et al to separate colloids and EVs using a pillar-constituent array with gap sizes ranging from 25 to 235 nm [95]. …”

Engineering solutions for cancer

“…Other areas where there is obvious potential for engineering input include: novel biosensors and pointof-care diagnostics for early detection of disease via the capture and detection of circulating biomarkers (liquid biopsies) [24][25][26][27]; the use of smart wearable or implantable electrochemical sensors to characterise tumour response to chemotherapy in situ or to monitor disease progression and/or signs of relapse [28,29]; artificial intelligence (AI), such as machine learning to help physicians make better diagnoses and guide treatment decisions while minimising costs [30]; metabolic and proteomic profiling of body fluids for the identification of tumoural areas in situ [31][32][33]; and disease-detecting or disease-fighting nanotechnologies (e.g. DNA nanobots [34], quantum dots [35]) for reporting disease status and selectively delivering drugs to tumour cells whilst minimising systemic side effects [36].…”