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Particle shape effects on subvisible particle sizing measurements.

Richard E Cavicchi1, Michael J Carrier, Joshua B Cohen

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Summary

Particle analysis instruments like flow imaging (FI) and electrical sensing zone (ESZ) show discrepancies with non-spherical particles. A new microfluidic device and algorithm improve accuracy for rod-shaped particle analysis.

Keywords:
electrical sensing zoneflow imagingimage analysislight obscurationlight scattering (static)microscopyparticle sizingphysical characterization

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Area of Science:

  • Analytical Chemistry
  • Materials Science
  • Biotechnology

Background:

  • Subvisible particle analysis (<100 μm) using light obscuration, flow imaging (FI), and electrical sensing zone (ESZ) shows discrepancies, especially with non-spherical particles.
  • Photolithography was used to create rod and disk-shaped particles to investigate shape effects on instrument performance.

Purpose of the Study:

  • To elucidate the causes of discrepancies and peak broadening in particle analysis instruments when characterizing non-spherical particles.
  • To develop and validate an improved correction algorithm for flow imaging (FI) to enhance accuracy for rod-shaped particles.

Main Methods:

  • Fabrication of rod and disk-shaped particles using photolithography.
  • Development of a microfluidic device for simultaneous electrical sensing zone (ESZ) and flow imaging (FI) measurements.
  • Implementation of an improved correction algorithm for FI to account for diffraction and focus effects.

Main Results:

  • Instruments produced broadened peaks and differing mean size parameters for monodisperse rod-shaped particles.
  • Particle alignment with flow caused oversizing by FI and undersizing by ESZ.
  • Observed particle tumbling in the microfluidic device led to oversizing and broader size distributions for rods.

Conclusions:

  • Particle shape significantly impacts subvisible particle analysis, causing discrepancies between different instruments.
  • The developed microfluidic device and improved FI algorithm reduce measurement discrepancies for rod-shaped particles.
  • Understanding particle orientation and tumbling is crucial for accurate subvisible particle characterization.