Particle Counters: Single Optical Particle Sizing

The history of particle counting can be traced back to the 1950’s when Wallace Coulter, an American electrical engineer and inventor discovered a method to count microscopic particles suspended in a fluid.

Coulter found that individual particles moving through an electric field created a change in flux, proportional to the size of the particle. However, while this principle worked well for particles with a narrow size range, such as blood cells, it had a major shortcoming when applied to particles with larger distributions.

This problem occurred because larger particles were too big to pass through the narrow orifice of Coulter’s particle counter, which was used for smaller particle distributions. This led to the discovery, by Professor David Nicoli, that a single particle could be measured by using a finely tuned laser source and a high gain detector.

Single particle optical sizing (SPOS)

The advantages of this new particle counter were threefold:

  1. There was no restriction to the size of the particle that could be measured.
  2. The dispersion medium did not have to be a conducting saline solution, meaning particles could now be measured in an aqueous or organic phase.
  3. Cell cleanout could now be automated and controlled dilution could be performed.

Measuring particle sizes

Typical size distribution techniques such as laser diffraction, use ‘ensemble’ calculations, where an algorithm is used to model the distribution. However, this can create a bias towards the finer end of the distribution. SPOS on the other hand, results in an absolute measurement and can pick up subtle changes in particle size distributions.

This absolute measurement is particularly important for applications such as emulsion stabilities and pharmaceutical injectable solutions, i.e. intravenous infusions, for example.

For critical applications, such as the production of injectable solutions, the FDA (Federal Drug Agency) specifies in Standard USP788, that a SPOS technique must be used.

Plotting particle size distributions

Particle size distributions can be plotted as the number of particles vs size or the volume weighted number of particles vs size. These distributions can be very different because of the 4/3πr3 factor that is applied.  Below you will see two plots of the same distribution, using these 2 different plots.

It is also important to show the concentration of particles in a distribution: SPOS is able to do this, whereas ‘ensemble’ particle counting methods can only display relative distributions.

When considering normal particle distributions, the concentration of particles will be in the range of millions/cm3. This concentration requires dilution to ensure only one particle is measured at one time. Alternatively, the new range of high concentration Fx detectors can be used.

As a last note, with contamination monitoring (looking for foreign bodies or oversize particles), it is necessary to process large volumes of the sample through the particle counter. This is because large samples are needed to pick up these low concentration, types of outliers. This can be performed by using an automated syringe driver to load the sample into the sensor.