Techniques for Nanoparticle Size Characterization – CD Bioparticles

Particle size, a crucial parameter for nano-pharmaceutical preparations, plays a significant role in determining their efficacy. To ensure the quality and effectiveness of these preparations, it is essential to measure and analyze their particle size and distribution accurately. This article explores various techniques for nanoparticle size characterization, including electron microscope technology, dynamic laser scattering, small-angle X-ray scattering, specific surface area method, and atomic force microscopy.

Electron Microscope Technology

One of the most versatile methods for observing and measuring particle size is electron microscope technology. Utilizing transmission electron microscopy (TEM) and scanning electron microscopy (SEM), this technique provides intuitive and reliable results. By using an electron microscope, one can observe the size and shape of nanometer drug delivery systems, estimate particle thickness based on image contrast, and analyze particle size distribution through image analysis. It is also possible to analyze the microstructure inside particles by embedding and slicing them into thin samples.

However, there are a few important considerations when performing electron microscope measurements. Firstly, the measured particle size may reflect the size of aggregates, so it is crucial to fully disperse the nanoparticle sample before preparing it for SEM. Secondly, the measurement results are not statistically representative due to the small amount of sample used in electron microscopy. Thirdly, it is important to note that electron microscopy provides particle size rather than grain size.

Dynamic Laser Scattering

Dynamic laser scattering, also known as photon correlation spectroscopy (PCS), is the most widely used method for analyzing the particle size of nanoparticles. This technique measures the diffusion coefficient of nanoparticles in a liquid to obtain particle size information. When nanoparticles are dispersed in a solvent, their Brownian motion causes them to diffuse in the solvent. The velocity of this Brownian motion is related to the particle size, as described by the Stokes-Einstein equation. By measuring the diffusion coefficient, one can calculate the particle size.

Laser diffraction particle size analyzers are more accurate for samples with a particle size larger than 5 μm, while dynamic light scattering particle size analyzers are suitable for nano and sub-micron particle samples with a size smaller than 5 μm. It is important to note that the shape and distribution characteristics of particles significantly impact the particle size analysis results. The more irregular the particle shape and the wider the particle size distribution, the larger the error in the analysis results. Laser particle size analysis offers advantages such as small sample consumption, automation, speed, repeatability, and online analysis. However, it is limited in analyzing high concentration systems due to interparticle interference.

Small-Angle X-ray Scattering Method

Small-angle X-ray scattering (SAXS) technology is a powerful technique for studying particles ranging from several nanometers to hundreds of nanometers. By analyzing the scattering pattern of X-rays at low angles, it is possible to obtain information about the long-period structure, shape, scale, or mass of submicron particles or pores. This technique is particularly useful for analyzing the spatial correlation of diffuse objects, such as polymer chains and macromolecules in solution.

Specific Surface Area Method

The specific surface area (Sw) of a nanopowder can be used to calculate the particle diameter, assuming the particles are spherical. The BET multilayer gas adsorption method is commonly used to measure the specific surface area. Nitrogen is typically used as the adsorbent, and the specific surface area ranges from 0.1 to 1000m2/g. This method provides information about the specific surface area of the nanopowder but does not reveal the particle size distribution.

Atomic Force Microscopy

Atomic force microscopy (AFM) offers a three-dimensional and high-resolution surface imaging of samples. By scanning the surface with a tiny probe, it converts the interaction between the probe and the sample into a topographical image. AFM not only measures particle size but also provides information about the shape of the sample. However, it has some limitations, including a small observation time and being time-consuming. Similar techniques include scanning transmission microscopy (STEM) and scanning transmission x-ray microscopy (STXM).

Selection of Particle Size Measurement Techniques

Nano drug delivery systems consist of particles of various sizes. Depending on the purpose of the measurement, the particle size distribution can be expressed in terms of number or volume diameter. The particle size distribution is influenced not only by the average particle diameter but also by the method used to evaluate it. Additionally, the shape of particles has a significant impact on the particle size distribution. It is recommended to select an appropriate measurement method based on the particle size range of interest, and multiple methods can be used to validate and cross-verify the results.

In conclusion, accurate nanoparticle size characterization is critical for evaluating the quality and effectiveness of nano-pharmaceutical preparations. By employing the appropriate techniques discussed in this article, researchers and scientists can gain valuable insights into the size and distribution of nanoparticles, ultimately contributing to the development of more efficient drug delivery systems.


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