Exosomes are nanometer-sized lipid vesicles present in liquid biopsies and used as biomarkers for several diseases including cancer, Alzheimer’s, and central nervous system diseases. Purification and subsequent size and surface characterization are essential to exosome-based diagnostics. Sample purification is, however, time consuming and potentially damaging, and no current method gives the size and zeta potential from a single measurement.
Here, researchers at the Technical University of Denmark concentrate exosomes from a dilute solution and measure their size and zeta potential in a one-step measurement with a salt gradient in a capillary channel. The salt gradient causes oppositely directed particle and fluid transport that trap particles. Within minutes, the particle concentration increases more than two orders of magnitude. A fit to the spatial distribution of a single or an ensemble of exosomes returns both their size and surface charge. This method is applicable for other types of nanoparticles. The capillary is fabricated in a low-cost polymer device.
Trapping of nanoparticles in a salinity gradient
a Schematic of the nanofluidic device with 16 funnel-shaped, parallel nanochannels connecting two microchannels. Pressure differences ΔP between the in- and outlets continuously drive buffers through the microchannels. Different salt concentrations CN and CW in the two microchannels at the narrow and wide ends of the nanochannels, respectively, establish a salt gradient across the nanochannels. Nanoparticles (red dots) are loaded in the microchannel with low salinity and some get trapped in the nanochannels. b, c Schematic top and side view of the funnel-shaped nanochannels, respectively. d Schematic of nanoparticle trapping in a funnel-shaped nanochannel by diffusioosmosis and diffusiophoresis. The gradient induces a diffusioosmotic fluid flow velocity νos and a diffusiophoretic particle velocity νph. Nanoparticles (red dots) get trapped around the position x0 where the fluid and particle velocities balance each other. The concentration of nanoparticles in the nanochannel is denoted Cp(x). e Composite fluorescence microscope image of trapped exosomes in the same nanochannel (outlined with yellow) for three different salinity gradients, that is, different ln(CN/CW) values. Images were averaged over 10 s. f Fluorescence intensity along the nanochannels for the data shown in e (blue points). Full, red lines are independent fits to Cp(x) in Eq. (7). Fit parameters are the diameter d and the zeta potential ζ. g Exosome diameters and zeta potentials from fits shown in f. Red, dotted lines are the weighted averages. Error bars are the standard errors on the means for measurements in three different nanochannels (n = 3).