ViroTEM

TEM-based analysis system

ViroTEM is an automated and versatile system for analysis and characterization of nanoparticles, viral-based biotherapeutics and other applications in biotherapeutic development and production.

ViroTEM delivers:

  • Rapid and efficient specimen searching (full grid overview) and high-resolution image acquisition enabled by a dual-camera system.
  • High-sample throughput via a “one touch” three specimen holder.
  • Broad range of applications made possible by the wide accelerating voltage range (20-120 kV).

Sytem overview

The ViroTEM analysis system comprises:

1. A 120 kV transmission electron microscope (TEM) with multiple lens configurations, including a standard lens for unsurpassed high contrast and a class-leading HR lens for high resolution. This innovative design allows for a wide variety of specialized applications.

2. Vironova Imaging and Analysis Software (VIAS) which provides semi-automatic image acquisition as well as subsequent analysis and data presentation. Pattern recognition and machine learning capabilities enable VIAS to perform advanced particle characterization, classification and measurements.

The combination of the advanced TEM-system together with VIAS software enables automated 2-level screening which allows the system to determine which grid squares are suitable for imaging and then acquires a series of high-resolution images at a pre-determined number of locations on the grid.

ViroTEM_HITACHI

Figure 1 - The ViroTEM system is compact TEM-based analysis tool designed for simple operation but with powerful functionality.

Main applications

The performance and versatility of the ViroTEM analysis system enables a large range of applications.

  • Determine particle size distributions of viral vectors and sample components.
  • Verify sample purity to verify downstream process capabilities and/or batch-to-batch variation.
  • Assess particle integrity when making changes in process conditions, including formulation buffers.
  • Visualize sample morphology to extract structural information about the sample.
  • Identify sample contaminants such as viruses (e.g. in cell bank characterization) or bacteriophage (e.g. in investigations of fermenter contaminations).

Semi-automated multilevel screening

The semi-automated, multilevel screening functionality of the ViroTEM involves four main steps:

HT7800-Figure_2_Step_1

Step 1

Acquire grid-square images at large field-of-view.
The system automatically adjusts to grid orientation.

HT7800-Figure_2_Step_2

Step 2

The system compares each image to reference image(s) to assess suitability for imaging.

HT7800-Figure_2_Step_3

Step 3

High-resolution images are obtained from grid squares that have been given a high suitability rating.

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Step 4

Images are analyzed to identify (i.e. segment) and classify particles.

Figure 2 - The ViroTEM multilevel screening methodology.

Reliable data analysis

The ViroTEM system translates TEM image data into quantitative analytics which can be used to make informed decisions in process development and manufacturing. Figure 3 shows an example of an analysis performed on adeno-associated viruses (AAVs).

HT7800-Figure_3-Example_analysis

Figure 3 - Analysis of internally-stained versus non-stained AAVs. Internally-stained vectors can be correlated to a loss of vector-integrity.

Secure data storage

The ViroTEM analysis systems stores data in a secure SQL database structure. The database can be located locally on the control PC, or can be installed in a network environment.

Summary

The ViroTEM analysis system is a powerful tool for biotherapeutic applications, especially those involving viral structures, including:

  • Gene therapy
  • Cell therapy
  • Viral-based vaccines
  • Virus and bacteriophage contaminations