Real-time modulated nanoparticle separation with an ultra-large dynamic range

Abstract

Nanoparticles exhibit size-dependent properties which make size-selective purification of proteins, DNA or synthetic nanoparticles essential for bio-analytics, clinical medicine, nano-plasmonics and nano-material sciences. Current purification methods of centrifugation, column chromatography and continuous-flow techniques suffer from particle aggregation, multi-stage process, complex setups and necessary nanofabrication. These increase process costs and time, reduce efficiency and limit dynamic range. Here, we achieve an unprecedented real-time nanoparticle separation (51-1500 nm) using a large-pore (2 μm) deterministic lateral displacement (DLD) device. No external force fields or nanofabrication are required. Instead, we investigated innate long-range electrostatic influences on nanoparticles within a fluid medium at different NaCl ionic concentrations. In this study we account for the electrostatic forces beyond Debye length and showed that they cannot be assumed as negligible especially for precise nanoparticle separation methods such as DLD. Our findings have enabled us to develop a model to simultaneously quantify and modulate the electrostatic force interactions between nanoparticle and micropore. By simply controlling buffer solutions, we achieve dynamic nanoparticle size separation on a single device with a rapid response time (<20 s) and an enlarged dynamic range (>1200%), outperforming standard benchtop centrifuge systems. This novel method and model combines device simplicity, isolation precision and dynamic flexibility, opening opportunities for high-throughput applications in nano-separation for industrial and biological applications.

Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

“…Recently, by considering the modulation of nanoparticle-pillar electrostatic interactions by the ionic strength of the buffer solution, separation of 51 nm and 190 nm particles with a gap of 2 μm between pillars was achieved, although no demonstration of biocolloid sorting at the nanoscale was made. 103 Wunsch et al . reported the first nano-DLD platform for separation of colloids and exosomes as small as 20 nm, made possible by fabrication of pillar arrays with gap sizes from 25 to 235 nm (Figure 3D).…”

A Review on Deterministic Lateral Displacement for Particle Separation and Detection

“…9c. Using the ultra-pure deionized water as the buffer, the nanoparticle separation of 50 nm from 190 nm in 2-µm-gap DLD has been demonstrated [66]. A force equation model (Eq.…”

Decorrelation correction for nanoparticle tracking analysis of dilute polydisperse suspensions in bulk flow

“…For example, the study of small molecule inhibitors that suppress microvesicle production are greatly benefited by accurate size measurements of dilute, polydisperse suspensions [33]. Similarly, microdevices using size-based separation methods to nanoparticle populations for downstream assaying must use accurate cutoff diameters in the design process [49][50][51]. Malvern Inc. recently developed the ability to perform simultaneous nanoparticle size, zeta potential and scattering intensity characterization [52].…”