Calibration-Less Sizing and Quantitation of Polymeric Nanoparticles and Viruses with Quartz Nanopipets

Abstract

The feasibility of using quartz nanopipets as simple and cost-effective Coulter counters for calibration-less quantitation and sizing of nanoparticles by resistive pulsing sensing (RPS) was investigated. A refined theory was implemented to calculate the size distribution of nanoparticles based on the amplitude of resistive pulses caused by their translocation through nanopipets of known geometry. The RPS provided diameters of monodisperse latex nanoparticles agreed within the experimental error with those measured by using scanning electron microscopy (SEM), dynamic light scattering (DLS), and nanoparticle tracking analysis (NTA). The nanopipet-based counter, by detecting individual nanoparticles, could resolve with similar resolution as SEM mixtures of monodisperse nanoparticles having partially overlapping size distributions, which could not be discriminated by DLS or NTA. Furthermore, by calculating the hydrodynamic resistance of the nanopipets and consequently the volume flow through the tip enabled for the first time the calibration-less determination of nanoparticle concentrations with nanopipets. The calibration-less methodology is applied to sizing and quantitation of inactivated poliovirus of ~26 nm diameter, which is the smallest size spherical shape virus ever measured by resistive pulse sensing.

Characterization of Nanopipettes

“…Method 1 assumes that the ratio between the outer and inner diameter of a nanopipette remains constant to that at the nanopipette opening, 13,41,52 and, as such, the inner nanopipette angle can be calculated by using the relationship:…”

“…Nanoelectrodes can also be fabricated by electrochemically plating nanopipettes with a variety of different metals. 12 Applications of nanopipettes include as tools for sizing, counting, [13][14][15][16][17] and sequencing of single particles or molecules. [18][19][20] These applications use the changes in ionic current through the end of the nanopipette (with an applied bias), as a single entity passes through the end of the probe, to provide diagnostic information.…”

Resistive-pulse and rectification sensing with glass and carbon nanopipettes

“…The Gyurcsányi group [75] used resistive-pulse sensing with quartz nanopipettes for sizing and quantitation of polymeric NPs and polioviruses. This approach was validated using the suspensions of monodisperse latex nanoparticles as well as mixtures of closely sized NP dispersions.…”

Nanoparticle displacement assay with electrochemical nanopore-based sensors

“…This sensing concept with single species detection capability has been studied for the determination of a wide variety of targets ranging from small ions [6] up to nanoparticles [6][7][8][9][10][11][12].…”