Dynamic Light Scattering for Cannabis Product Development

September 12, 2020
What is DLS?

Dynamic light scattering (DLS) is a rapid and non-invasive analytical technique for determining the size of particles and macromolecules in an emulsion or colloidal system. DLS enables measurement of particle size distributions ranging from less than a nanometer up to several microns in size. The DLS technique finds use in the cannabis industry to help improve and characterize product formulations. Read about how one leader uses DLS in his product development process here.

In DLS a laser is used to measure Brownian motion of particles in a dispersion. Brownian motion is the random movement of particles which results from their collision with solvent molecules such as water. Smaller particles diffuse, or move more quickly. Larger particles diffuse more slowly. The rate of Brownian motion is quantified as the translational diffusion coefficient, D.

A dispersion is a mixture containing a dispersed substance in a medium. As an example, chocolate milk is a dispersion of chocolate particles in milk.

Hydrodynamic particle size, as measured by DLS, is defined as the size of a sphere that diffuses at the same rate as the particle being measured. This sphere comprises of a core particle plus anything which is bound to its surface for example any ions or absorbed polymers.

Hydrodynamic particle size illustrations. Left: particle surrounded by ions forming a hydration layer. Right: particle with adsorbed polymer forming a hydration layer.

When the particles are subjected to a laser the particles scatter some of the light that hits them. This light scattering is received by a detector at an experimental angle, theta, from the laser. The detector outputs a light intensity vs time plot which is passed to a correlator.

DLS experimental setup. A laser irradiates the sample. Detector at angle theta receives the scattering signal. An Intensity vs Time plot is generated and passed to a correlator.

In a dispersion, diffusion causes the intensity of light scattered by the particles to fluctuate over time. The speed of these intensity fluctuations depends on the particle’s diffusion rate. Smaller particles will more quickly diffuse which translates to more rapid fluctuations in scattered light. Larger particles will more slowly diffuse which translates to less rapid fluctuations in scattered light. This is how Brownian motion affects particles of different sizes and how the scattered light will fluctuate over time. Particle size can be determined using this information.

Intensity vs Time plots for small particle (left) and large particle (right).

In a process called auto-correlation, rapid snapshots of the scattering signal are taken comparing back to the original signal measured. Between consecutive snapshots which are on the scale of nano or microseconds, the intensity signals are very similar or well correlated. When we look at snapshots which are further apart in time the similarity or correlation begins to decrease. Eventually the intensity signal changes completely and there is no longer any correlation with the original signal. This process is called autocorrelation. The larger the particles being measured the more slowly they diffuse and the longer it takes for complete loss of the correlation signal. Small particles which undergo rapid diffusion the correlation of the signal will decay rapidly.

Correlation coefficient vs Time graph for small particle (green) and large particle (orange).
How do we calculate particle size?

The auto-correlation function we’ve created enables us to extract the translational diffusion coefficient, D, which was mentioned earlier. These values are used in the Stokes-Einstein equation to obtain our size information. Variables such as viscosity and temperature need to be known as they will affect the diffusion rate.

Stokes-Einstein Equation. Hydrodynamic diameter can be calculated if Absolute temperature, viscosity and diffusion coefficient, D, are known.

Using DLS we can quickly measure the size of all the particles in a sample. Size distribution measured as shown in graph as an intensity distribution. This is the primary result and it shows the intensity of scattered light from each size population present in the sample. These results can also be converted into a volume or number number-size distribution if need be.

Intensity vs Size plot for an emulsion with two different particles (one small and one large).

Particle size and distributribution are important data points in understanding product stability, onset time and evenness of dosing. DLS is an important technique in the analytical toolkit that can help to characterize and understand the stability of cannabis nanoparticles in an emulsion.

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