Density Measurements of Single Granules Using the Atomic Force Microscope

Abstract

The density of single spray‐dried granules has been determined with a new method based on atomic force microscopy (AFM). Spherical granules with a well‐defined diameter are attached to the AFM cantilever, which acts as a beam‐type spring, and the mass of a granule is estimated from the shift in the resonant frequency. The error of the measurements associated with the method was estimated to vary between 1% and 5%, depending on the size and shape of the granule. Density measurements of spray‐dried WC–Co granules are presented, and the effect of a polymeric binder and dispersant on the consolidation during drying is discussed.

Applications of the Atomic Force Microscope in the Development of Propellant-based Inhalation Formulations

“…A summary of the studies is given in Table 1. We also address other measurements that can be made with the AFM and that are of potential interest to pMDIs such as determination of particle density 81,82) and Hamaker constant 59,83) .…”

“…A novel method based on the CPM technique has been suggested to determine the density of particles 81,82) . A single spherical particle is initially glued onto the AFM cantilever as in a typical CPM experiment.…”

An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles

“…The method has been described in detail elsewhere. 6 In short, the method is based on the principles of an oscillating spring. An AFM cantilever is a beam type Hookean spring, the motion of which is described by the fundamental resonant frequency (n 0 ) the effective mass of the cantilever (m eff ) and the spring constant (k):…”

“…Care was taken to always place the particles in the same position on the cantilever, to minimize the measurement error. 6 The measurement to determine the weight of a particle was carried out once for each particle, and hence no error limits for the determination can be given. It has been carefully controlled that the addition of the ointment does not significantly influence the resonant frequency of the cantilever.…”

AFM-Porosimetry: Density and Pore Volume Measurements of Particulate Materials

“…The principle is to use AFM cantilevers as balances to measure the weight of single particles. AFM cantilevers have been used as mass sensors in a range of applications since the resonant frequency of the cantilever is sensitive to the attached mass. – Thermal vibrations make the cantilevers oscillate, and a resonant frequency of each cantilever can be measured by AFM. The mass is then obtained from the shift in resonant frequency of the cantilevers with and without particles attached.…”