Draft:Spatially Resolved Dynamic Light Scattering

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Spatially Resolved Dynamic Light Scattering (SR-DLS) is a particle size measurement technique that can be used to measure sub-micron particles dispersed in a liquid, including nanoparticles, colloids, polymers and emulsions. SR-DLS was first described in 2019 on European Journal of Pharmaceutical Sciences.[1] This technique is based on Dynamic Light Scattering (DLS) and Optical Coherence Tomography (OCT), which allows resolving the scattered light signal from a suspension in depth. This enables the measurement of highly turbid samples, as it is possible only to use signals from depths without multiple scattering.[2] Furthermore, SR-DLS also allows measuring particle size in flow, as the flow profile inside the tubing can be resolved and corrected.[1] Therefore, SR-DLS can be used as an inline particle sizing technique for sub-micron particles.

Setup[edit]

A broadband light source is split between a reference beam and a sampling beam. The sampling beam is then used to illuminate a sample volume, in which particles are diffusing by Brownian motion. The scattering signal is then collected at full backscattering (180°) and directed onto an interferometer. Fourier Domain Low-Coherence Interferometry (FDLCI)[3] is then employed to extract depth-resolved information from the interference pattern. This information is the intensity fluctuations of the scattered signal at each sample depth, which are then individually analyzed and treated as regular DLS data to obtain a particle size distribution at each depth.

SR-DLS vs DLS: Advantages[edit]

The ability to spatially resolve the scattering signal from a suspension allows for a number of applications:

Higher turbidity limits and multiple scattering filtering[edit]

SR-DLS allows particle size measurement in highly turbid samples (thousands of NTU).[2] This is a direct result of the ability to determine at which depth in the sample the contribution of multiple scattering into the scattering signal becomes relevant. A particle size distribution is calculated at each depth during an SR-DLS measurement, which will become distorted if the contribution of multiple scattered photons becomes relevant.[4] For very turbid samples, this particle size distribution becomes distorted the deeper the signal depth. By analyzing the particle size distribution at each depth it can be determined from which point the measurement is not reliable.

Particle size measurement of flowing dispersions[edit]

By resolving in depth and performing SR-DLS measurements, a correlation function is obtained at each depth.[1] As in standard DLS, the diffusion constant of the particles is calculated from the correlation function.[5] A dispersion under laminar flow will present increasing flow velocities farther from the tubing walls.[6] A standard DLS measuring a flowing dispersion faces the challenge of calculating particle size from a dispersion with Brownian motion and a concurrent complex flow profile, which is not readily achievable and severely limits its measurements. If flow correction is not applied, particles will display Brownian and additional flow velocities and the particle size will be underestimated. SR-DLS allows for the reconstruction of the flow profile velocities inside tubing by evaluating the change in particle velocity in depth. This flow profile is then used to correct depth-by-depth the DLS measurement, yielding a purely Brownian-motion based particle size measurement.

Technical limitations of SR-DLS[edit]

Flow rate limits[edit]

DLS-based systems quantify the diffusion constant of a dispersion, its particles have to diffuse a minimum distance with respect to the illuminating wavelength. In a flowing dispersion each particle is only be present in the illuminated volume for a time that depends on the speed of the flowrate.[1] Therefore, above certain flowrates it will not be possible to characterize the size of nanoparticles. Furthermore, larger particles have lower diffusion constants and slower flow rates will increasingly affect their measurement.

References[edit]

  1. ^ a b c d Besseling, R.; Damen, M.; Wijgergangs, J.; Hermes, M.; Wynia, G.; Gerich, A. (2019-05-15). "New unique PAT method and instrument for real-time inline size characterization of concentrated, flowing nanosuspensions". European Journal of Pharmaceutical Sciences. 133: 205–213. doi:10.1016/j.ejps.2019.03.024. ISSN 0928-0987. PMID 30928511.
  2. ^ a b "Continuous Size Monitoring of Turbid Titanium Dioxide Nanosuspensions with the Nanoflowsizer". AZoNano.com. 2021-08-31. Retrieved 2023-11-20.
  3. ^ Wax, Adam; Yang, Changhuei; Izatt, Joseph A. (2003-07-15). "Fourier-domain low-coherence interferometry for light-scattering spectroscopy". Optics Letters. 28 (14): 1230–1232. Bibcode:2003OptL...28.1230W. doi:10.1364/ol.28.001230. ISSN 0146-9592. PMID 12885030.
  4. ^ Ragheb, Ragy; Nobbmann, Ulf (2020-12-10). "Multiple scattering effects on intercept, size, polydispersity index, and intensity for parallel (VV) and perpendicular (VH) polarization detection in photon correlation spectroscopy". Scientific Reports. 10 (1): 21768. Bibcode:2020NatSR..1021768R. doi:10.1038/s41598-020-78872-4. ISSN 2045-2322. PMC 7729959. PMID 33303864.
  5. ^ Berne, Bruce J.; Pecora, Robert (2000-01-01). Dynamic Light Scattering: With Applications to Chemistry, Biology, and Physics. Courier Corporation. ISBN 978-0-486-41155-2.
  6. ^ Lagerstrom, P. A. (1996-06-02). Laminar Flow Theory. Princeton University Press. ISBN 978-0-691-02598-8.
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