Gold nanoparticles are one of the most popular and extensively researched type of nanoparticle. A Google Scholar search of the term “gold nanoparticles” results in over 500,000 hits. Applications range from the biological to the material, and include nanomedicine, drug delivery, cancer diagnostics, biological scaffolds, biosensors, contrast agents, catalysts, and CMP slurries for the manufacturing of microprocessors
This wide ranging application space is made possible by their versatile optical properties, compatibility with a variety of surface chemistries, and their well-studied synthesis and preparation.
Common characterization tools include transmission or scanning electron microscopy (TEM/SEM), dynamic light scattering (DLS), and Ultra Violet-Visible absorbance (UV-Vis). These tools provide a high degree of information. For example, UV-Vis can be used to measure shifts in the surface plasmon resonance absorbance to monitor surface conjugation and aggregation state, but provides little direct information about particle size. TEM and SEM can provide extremely high resolution images for size and shape determination, but requires extensive sample preparation and cannot analyze particles in suspension. DLS is a ubiquitous technique to rapidly measure particle size, but it cannot measure particle concentration and lacks the resolution to resolve multiple populations of similarly sized particles. These are important characterization tools, but ultimately are limited in that they cannot provide high resolution size distributions or particle concentrations of colloidal particles in solution.
Nanoparticle Tracking Analysis (NTA) utilizes the properties of both light scattering and Brownian motion in order to obtain the particle size distribution of samples in liquid suspension. A laser beam is passed through the sample chamber, and the particles in suspension in the path of this beam scatter light in such a manner that they can easily be visualized via a 20x magnification microscope onto which is mounted a camera. The camera, which operates at approximately 30 frames per second, captures a video file of the particles moving under Brownian motion within the field of view of approximately 100 µm x 80 µm x 10 µm.
The movement of the particles is captured on a frame-by-frame basis. The proprietary NTA software simultaneously identifies and tracks the center of each of the observed particles, and determines the average distance moved by each particle in the x and y planes. This value allows the particle diffusion coefficient to be determined from which, if the sample temperature and solvent viscosity are known, the sphere equivalent hydrodynamic diameter of the particles can be identified using the Stokes-Einstein equation.
In addition, the particles’ movement is measured within a fixed field of view (approximately 100 µm by 80 µm) illuminated by a beam approximately 10 µm in depth. These figures allow a scattering volume of the sample to be estimated; by measuring concentration of the particles within this field of view and extrapolating to a larger volume it is possible to achieve a concentration estimation in terms of particles per mL for any given size class or an overall total.
As a result, NTA can be used as a rapid and routine characterization tool that has the resolution to distinguish between multiple populations of similarly sized particles, the sensitivity to detect size differences before and after modifying surface chemistry, and directly counts particles to provide gold nanoparticle dosimetry in therapeutic applications.
Here we present examples of different types of gold nanoparticle samples characterized by NTA.