Electron microscopy services
Specialized for biopharmaceuticals

Electron microscopy services

Vironova is a service provider specialized in transmission electron microscopy (TEM) analysis of vaccines, gene therapy and drug delivery particles such as viruses and liposomes. Vironova offers a complete GMP-compliant TEM analysis package that includes both negative stain (nsTEM) analysis and cryogenic (cryoTEM) analysis, each providing powerful image datasets, quantitative data, and conclusions from the analysis.

TEM – unmatched technology

Sample purity, particle size, shape and overall morphology are often directly correlated to the efficacy and safety of the end drug product. TEM is an unmatched technology for visualizing and understanding particle characteristics and seeing what actually happens when conditions are changed in upstream and downstream processes or product formulations.

Detect Debris
Detect aggregates
Reveal particle integrity status

Vironova Analyzer software – designated for TEM image analysis

Our service team uses the in-house developed Vironova Analyzer software (VAS) for the analysis of TEM images of nanoparticles. The software automates the extraction of morphological data and measurements from the TEM images for graphical presentation. The automation that VAS provides allows Vironova EM services to deliver high-quality images and accurate quantitative data timely and cost-effectively.

Learn more about VAS


VAS Screen


Validated AAV percentage full capsid analysis

Virus particle packaging analysis with cryoTEM in combination with VAS is a patented method and the first validated method in the world for AAV percentage-full-capsid analysis. This method is recommended for batch release testing and QC of AAV based gene therapy products.



Simply send your sample to the TEM experts

Our experts will tailor the analysis to address your specific questions.

The report will contain:

  • Representative EM-images
  • Quantitative analysis
  • Concluding summary with comments from the expert team

Gene therapy & Viral based Vaccines

Size distribution analysis
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MiniTEM automates imaging, AAV particle detection and measurements to present accurate size distribution data

MiniTEM™ can reveal contaminants in AAV samples, for example proteosomes in the figure below.


In the above graph an overlay of the results from MiniTEM and DLS analysis of the same sample is shown. DLS was in this case not able to distinguish between AAV particles and the proteasomes.

Size distribution study with MiniTEM can also reveal small size debris and aggregates

Level and size of aggregates

The size distribution graph shows the number of particles of expected size as well as smaller size debris and aggregates – the data is easily correlated to what is revealed in the acquired images.

Purity analysis
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Automated size distribution analysis can be used to detect level of debris and compare the purity of different AAV samples

Level of debris

The box-plot shows purity measurement of the two samples calculated as the ratio of the total area of debris to Adenovirus particles.

Virus integrity status
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MiniTEM can be used to automatically quantify disrupted empty AAV particles

Virus particle morphology

TEM analysis of negatively stained AAV samples (nsTEM) is a reproducible method for revealing particles with disrupted capsid structure. Disrupted particles take in stain and can therefore be identified by their darker centres. 


Comparing particle integrity of two AAV samples in MiniTEM:

Integrity graphs

Integrity states


Comparing particle integrity of Adenovirus samples in MiniTEM:

Integrity ratio


Below is an analysis of MuLV (murine leukemia virus). The numbers of circular intact particles with preserved morphology, of non-circular particles morphologically affected by the processing, and of debris, are compared.

MuLV debris

Detailed virus morphology
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Examples of details in virus morphology revealed with nsTEM


Virus integrity before Virus integrity after
Rotavirus Influenza


Influenza spike proteins

Influenza virus protein


Percentage full AAV capsids
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The VAS software in combination with cryoTEM accurately distinguishes between full and empty AAV particles

Cryo EM Cryo EM graph

The output of VAS analysis is a report with quantitative data.


Cryo EM table



Drug delivery

Particle size distribution
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Size distribution of liposomes detected with VAS

Morphology including circularity
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Shape (circularity) distribution analysis of liposomes detected by VAS

Packaging efficiency (full/empty ratio)
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VAS software allows objective determination of drug content of liposomes

The VAS software measures whether the liposomes contain the drug or not. The program then presents a bar chart. The output of VAS analysis is a report with quantitative data.

Liposomal lamellarity
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VAS is employed to quantify lamillarity classes

Thickness of liposomal bilayer
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High magnification cryoTEM of liposomes supports measurements of bilayer thickness

The graph shows the thickness distribution in nm.


Particle size distribution of recombinant proteins
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MiniTEM is employed for size distribution analysis of recombinant proteins to detect deviations in size

The size distribution graph shows the number of particles of expected size as well as smaller size debris and aggregates – the data is easily correlated to the content of the acquired images.

Aggregate & particle detection
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TEM imaging of different samples of monoclonal antibodies (mAbs)

Single mAbs in a monolayer can be observed as well as stress induced aggregates.

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