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Related Concept Videos

Microorganisms in Medicine and Therapeutics01:29

Microorganisms in Medicine and Therapeutics

Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
Vaccine Production01:23

Vaccine Production

Vaccine production involves a sequence of upstream and downstream processes to generate a safe and effective immunological product. It begins with cultivating microorganisms, such as viruses or bacteria, to obtain antigenic material. For viral vaccines, mammalian host cells are grown in bioreactors and subsequently infected with the target virus. The virus replicates within the host cells, which are lysed to release viral particles. This lysate is then clarified through filtration or...

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Related Experiment Video

Updated: May 7, 2026

A Technique to Simultaneously Visualize Virus-Specific CD8+ T Cells and Virus-Infected Cells In situ
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In Situ Microscopy for Real-Time Visualization of Microcarrier Cell Cultures for Live Virus Vaccine Process

Justin P Lomont1, Tracy N Love1, James M Wagner1

  • 1Process Research & Development, MRL, Merck & Co. Inc., West Point, Pennsylvania, USA.

Biotechnology and Bioengineering
|January 5, 2026
PubMed
Summary
This summary is machine-generated.

In situ microscopy offers real-time insights into microcarrier cell culture for live virus vaccine production. This novel Process Analytical Technology (PAT) reveals critical phenomena like microcarrier aggregation, often missed by traditional methods.

Keywords:
Process analytical technologybioreactor cell culturein situ microscopylive virus vaccinereal time imagingupstream process developmentvaccines

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Area of Science:

  • Biotechnology and Bioprocessing
  • Vaccine Manufacturing
  • Process Analytical Technology (PAT)

Background:

  • Microcarrier (MC) cell culture is crucial for live virus vaccine (LVV) production.
  • Characterizing critical process phenomena (e.g., cell lysis, MC aggregation) in real-time is challenging.
  • Traditional offline methods may not accurately represent dynamic cell culture conditions.

Purpose of the Study:

  • To introduce in situ microscopy as a novel Process Analytical Technology (PAT) for upstream LVV cell culture.
  • To enable real-time visualization and characterization of cell and microcarrier behavior.
  • To overcome limitations of traditional offline analysis in bioprocess monitoring.

Main Methods:

  • Utilized two commercially available probe-based in situ microscopy technologies.
  • Applied in situ microscopy directly within the bioreactor for real-time data acquisition.
  • Compared in situ microscopy findings with traditional offline microscopy methods.

Main Results:

  • Successfully visualized and characterized key phenomena including cell growth, death, detachment, debris accumulation, and MC aggregation in real-time.
  • Observed significant microcarrier aggregation, particularly during viral replication, which was not detected by offline analysis.
  • Highlighted potential disruption of MC-aggregate structures during manual sampling in offline methods.

Conclusions:

  • In situ microscopy is a powerful PAT tool for accurate, real-time characterization of upstream LVV processes.
  • Microcarrier aggregation is a prevalent, previously underestimated phenomenon in MC-based LVV cultures.
  • This technology advances process understanding beyond traditional offline characterization methods.