Macro mass photometry

Qualitatively characterize large viral vectors for use in cell and gene therapy and vaccine development.

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How can I learn more about macro mass photometry?

To read more about the science behind this innovative analytical technology, download the white paper. 

To read more about Refeyn’s macro mass photometry instrument, visit the KaritroMP product page.  

Reducing delays in viral vector characterization

Conventional viral vector characterization techniques create a significant bottleneck in cell and gene therapy and vaccine development workflows. Cell-based assays take days to perform and nanoparticle tracking assays (NTA), while faster, only provide limited data.

Macro mass photometry is a fast, accurate and easy way to characterize large viral vectors, like adenoviruses (AdV) and virus-like particles (VLPs), providing information to inform and optimize process development, including:

• Full/empty capsid ratios

• Particle morphology (size distribution)

• Sample purity

• Vector stability/degradation

Efficient bioanalysis of large viral vectors

Speed

Get results within minutes for rapid decision-making

 

Label free

Eliminate dyes and extensive sample prep

Versatility

Assess sample suitability at any step for downstream processing

Cost-efficiency

Detect quality issues early, saving time and money

Comprehensive analysis

 Measure vector purity and subpopulations within a sample

Innovative technology driving therapeutic development

Macro mass photometry is the technology that powers Refeyn’s KaritroMP instrument, creating a next-generation tool for the analysis of large viral vectors and virus-like particles.  

Developed by Refeyn, macro mass photometry builds on the strong foundation of mass photometry – Refeyn’s game-changing single-particle mass measurement technology. Like mass photometry, macro mass photometry combines sophisticated optics and precise image processing to deliver an illuminating yet user-friendly analysis experience. It performs single-particle, multiparametric analysis in minutes, in solution, with no need for labelling or other time-consuming sample preparation steps.  

By measuring particle size and relative mass, macro mass photometry reveals particle subpopulations and distributions in a sample. It gives valuable insights into sample purity, stability and composition – going beyond what can typically be obtained using other methods while using less time and sample.  

Comparing macro mass photometry to mass photometry

Both technologies

  • Operate in solution
  • Operate without the need for labels
  • Provide data at the level of single molecules or particles
  • Are based on principles of interference reflection microscopy and interferometric scattering microscopy

Mass photometry vs.
macro mass photometry

  • In mass photometry, contrast is coverted directly to mass; in macro mass photometry, it is a proxy for mass
  • While both techniques measure contrast, only macro mass photometry measures particle size
  • Mass photometry is suitable for measuring smaller particles (proteins, nucleic acids, AAVs); macro mass photometry measures larger particles (AdVs, VLPs)
Mass photometry Macro mass photometry

Particle type

Biomolecules (proteins, nucleic acids, etc.), AAVs
Large viral vectors (AdVs, VLPs)

Particle range

30 kDa – 6 MDa mass, << λ of light (Rayleigh regime)
40 – 150 nm diameter, ≈ λ of light (towards Mie regime)

Parameters measured

Mass (directly proportional to contrast)
Contrast, Diameter

What is visualized

Particles landing (ratiometric approach)
Immobilized particles (non-ratiometric approach)

Data outputs

Mass histogram
Contrast histogram, Size histogram, Size-contrast scatter plot

Streamline viral vector characterization

Adenoviral vector characterization

Detect sample impurities with confidence

Macro mass photometry analysis detects full adenovirus versus helper adenovirus, an important impurity that must be removed as part of downstream processing to reduce immunogenicity in cell and gene therapies.

See the data in our white paper.

Accelerating vector analysis

The KaritroMP macro mass photometer is a powerful benchtop instrument that can be used to characterize large viral vectors (like adeno, lenti and VLPs) in minutes.

Visually resolve distinct vector populations and reveal changes over time during R&D and process development to optimize vector production.

Advances in Cell and Gene Therapy: Characterizing Large Viral Vectors Using Macro Mass Photometry

Learn how macro mass photometry facilitates rapid qualitative analysis of single viral particles, useful for comparing production and purification methods and detecting batch variations in cell and gene therapy development and manufacturing.

Speeding up gene therapy analytics

Macro mass photometry for rapid viral vector characterization

Discover how macro mass photometry addresses the bottleneck of vector characterization, helping to accelerate cell and gene therapy and vaccine development and manufacturing workflows.

Frequently asked questions

What is ‘contrast’ in macro mass photometry?

Particle scattering contrast (‘contrast’ for short) is a proxy for particle mass. The contrast provides a way to differentiate particles that would not be resolvable based on size alone.

What does macro mass photometry measure?

Macro mass photometry analyzes individual particles, providing data on two parameters simultaneously: Particle scattering contrast (a proxy for mass) and size (diameter).

How does macro mass photometry compare to mass photometry?

Macro mass photometry builds on the physical principles used in mass photometry and introduces an additional measurement parameter: Size. In contrast to mass photometry, macro mass photometry is optimized for characterizing larger particles, such as adenoviruses (AdV), lentiviruses and virus-like particles (VLPs). 

References

[1] G. Young et al., ‘Quantitative mass imaging of single biological macromolecules’, Science, vol. 360, no. 6387, pp. 423–427, Apr. 2018, doi: 10.1126/science.aar5839

[2] D. Cole, G. Young, A. Weigel, A. Sebesta, and P. Kukura, ‘Label-Free Single-Molecule Imaging with Numerical-Aperture-Shaped Interferometric Scattering Microscopy’, ACS Photonics, vol. 4, no. 2, pp. 211–216, Feb. 2017, doi: 10.1021/acsphotonics.6b00912

[3] H. Verschueren, ‘Interference reflection microscopy in cell biology: methodology and applications’, Journal of Cell Science, vol. 75, pp. 279–301, Apr. 1985, doi: 10.1242/jcs.75.1.279

[4] J. Ortega-Arroyo and P. Kukura, ‘Interferometric scattering microscopy (iSCAT): new frontiers in ultrafast and ultrasensitive optical microscopy’, Physical Chemistry Chemical Physics, vol. 14, no. 45, pp. 15625–15636, 2012, doi: 10.1039/c2cp41013c

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