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Scanning Transmission Electron Microscopy Tomography in Virology: 3D Imaging of High-pressure Frozen, Freeze-substituted Samples
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Scanning Transmission Electron Microscopy Tomography in Virology: 3D Imaging of High-pressure Frozen, Freeze-substituted Samples

Published on: August 6, 2025

Optical coherence tomography-based freeze-drying microscopy.

Mircea Mujat1, Kristyn Greco, Kristin L Galbally-Kinney

  • 1Physical Sciences, Inc., 20 New England Business Center, Andover, MA 01810, USA. mujat@psicorp.com

Biomedical Optics Express
|January 19, 2012
PubMed
Summary
This summary is machine-generated.

A novel freeze-drying microscope using optical coherence tomography (OCT-FDM) enables real-time 3D imaging of pharmaceutical formulations. This technology accurately determines the critical collapse temperature during freeze-drying, crucial for process design.

Keywords:
(110.0180) Microscopy(110.4500) Optical coherence tomography(180.6900) Three-dimensional microscopy

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Area of Science:

  • Pharmaceutical Sciences
  • Biomedical Engineering
  • Materials Science

Background:

  • Freeze-drying (lyophilization) is a critical process for pharmaceutical product stability.
  • Monitoring structural changes and collapse temperature in situ is essential for optimizing lyophilization cycles.
  • Current methods for monitoring freeze-drying processes lack real-time, high-resolution imaging capabilities.

Purpose of the Study:

  • To introduce a new time-domain optical coherence tomography freeze-drying microscope (OCT-FDM).
  • To demonstrate the capability of OCT-FDM for real-time, in situ 3D imaging of pharmaceutical formulations during freeze-drying.
  • To correlate structural changes with temperature to determine the critical collapse temperature.

Main Methods:

  • Development of a novel freeze-drying microscope integrating time-domain optical coherence tomography.
  • Real-time, in situ 3D volumetric imaging of pharmaceutical formulations within vials.
  • Simultaneous measurement of product temperature during the freeze-drying cycle.

Main Results:

  • Achieved lateral resolution of <7 μm and axial resolution of <5 μm for 3D imaging.
  • Successfully correlated volumetric structural imaging with product temperature.
  • Identified the critical temperature at which the freeze-dried cake undergoes collapse.

Conclusions:

  • The OCT-FDM microscope provides unprecedented real-time, in situ 3D structural insights into pharmaceutical freeze-drying.
  • This technology enables accurate determination of the critical collapse temperature, a key parameter for process optimization.
  • OCT-FDM is a valuable tool for advancing the design and control of pharmaceutical freeze-drying processes.