When a nanoparticle enters a microcavity it interacts with the light present by introducing a local change to the refractive index relative to the surrounding fluid. This change has two effects on the light in the cavity.
Firstly it modifies the optical path length per round trip of the cavity so that the wavelength of the stored light shifts.
Secondly it results in the scattering of light from the cavity, increasing the optical loss rate, which results in attenuation and spectral broadening of the light stored by the microcavity.
Both of these phenomena can be measured by scanning the cavity through resonance with a laser.
The magnitude of these effects is determined by the degree to which the nanoparticle is electrically polarised by the optical field in the cavity. The polarisability of the nanoparticle depends on its size and the ratio of its refractive index to that of the surrounding fluid. For small particles it is advantageous to measure the wavelength shift rather than attenuation. This is the key parameter used by Oxford HighQ nanoparticle analysers.
The magnitude of the shift depends on the position of the particle within the microcavity, such that the maximum value only occurs when the particle is at the location where the optical field is most intense. The position of a particle will change over time as the nanoparticles undergoes random Brownian motion in the fluid. The Oxford HighQ nanoparticle analyser measures the wavelength shift several thousand times per second to capture the changing position of the particle.
The speed of the Brownian motion is determined by the viscous drag of the fluid acting on the particle, which in turn depends on the size of the particle. The measured dynamics therefore provide information about the size of the nanoparticle. Accurate quantitative measurements are facilitated by trapping individual particles in the microcavity using the optical tweezers effect.
One of the key applications for nanoparticle characterisation is that we can demonstrate drug unloading measurements of active pharmaceutical ingredients (APIs) on a particle-by-particle basis. We have successfully demonstrated our ability to accurately measure the drug offloading profile of cetylpyridinium chloride (CPC) from mesoporous silica nanoparticles (see Figure 2) and further details are available on our nanomedicine page or by downloading our application note.
Figure 3. Measurement principle for characterisation of nanoparticles for nanomedicine
Figure 1. Prototype Nanoparticle Analyser
Figure 2. Line graph showing decrease in drug loading (in μg/mg) over time, with a steady decrease from time 0 until 40 minutes. Shadowed regions represent 15th to 85th percentile