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Detection and Sizing of Submicron Particles in Biologics With Interferometric Scattering Microscopy.

Authors
  • Wong, Nathan A1
  • Uchida, Nina V1
  • Dissanayake, Thilini U1
  • Patel, Mehulkumar2
  • Iqbal, Maira1
  • Woehl, Taylor J3
  • 1 Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, College Park, Maryland 20742.
  • 2 Division of Biology, Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
  • 3 Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, College Park, Maryland 20742. Electronic address: [email protected]
Type
Published Article
Journal
Journal of Pharmaceutical Sciences
Publisher
Elsevier
Publication Date
Jan 01, 2020
Volume
109
Issue
1
Pages
881–890
Identifiers
DOI: 10.1016/j.xphs.2019.05.003
PMID: 31160046
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

We demonstrate the application of interferometric scattering microscopy (IFS) for characterizing submicron particles in stir-stressed monoclonal antibody. IFS uses a layered silicon sensor and modified optical microscope to rapidly visualize and determine the particle size distribution (PSD) of submicron particles based on their scattering intensity, which is directly proportional to particle mass. Limits for particle size and optimal solution concentration were established for IFS characterization of submicron particles. We critically compare IFS data with dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and find IFS is superior to NTA and DLS for determining the realistic shape of the number-based PSD, whereas NTA and DLS provide superior information about absolute particle size. Together, IFS, NTA, and DLS provide complementary information on submicron particles and enable quantitative characterization of the PSD of submicron aggregates. Finally, we explore quantifying particle size with IFS by developing a calibration curve for particle scattering intensity based on correlative scanning electron microscopy imaging. We found that only a subset of isotropic-shaped particles followed the expected proportionality between IFS intensity and particle mass. Overall, this study demonstrates IFS is a simple approach for detecting and quantifying submicron aggregate PSD in protein-based therapeutics. Copyright © 2020 American Pharmacists Association®. All rights reserved.

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