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Short answer: mass photometry is a label-free method that measures the mass of individual biomolecules in solution by detecting the light each one scatters when it lands on a glass surface. Because the scattering signal is proportional to a molecule’s mass, a sample’s mixture of species (monomers, dimers, larger assemblies) appears as separate peaks in a mass histogram built from single-molecule counts.
Definition and scope
Refeyn, the instrument manufacturer, describes mass photometry as a technique that measures the light scattered by individual particles. Light scattered by a molecule that has landed on the measurement surface interferes with light reflected from that surface, and the strength of that interference signal scales with the molecule’s mass. Each landing event is one data point, so the result is a count-based distribution of masses rather than a single averaged value.
The same source states that measurements are made on molecules in their native state, in solution and without labels, and that the approach is compatible with membrane proteins. Analytes it lists include proteins, glycoproteins, nucleic acids, antibodies, adeno-associated viruses (AAVs), virus-like particles and membrane proteins. The applications it names are sample purity and homogeneity, oligomerization, biomolecular interactions and complex assembly.
Where the name comes from
The underlying approach was described in a 2018 paper in Science (Young et al., 360(6387):423-427, DOI 10.1126/science.aar5839, PMID 29700264) under the name interferometric scattering mass spectrometry (iSCAMS). Its abstract reports that the authors used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution and 1-kilodalton precision, resolved oligomeric distributions, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. Manufacturer material and trade press now call the technique mass photometry.
How it works in practice
A Lab Manager trade article gives the practical profile of a measurement:
- Sample: 5 to 20 µL of sample at low nanomolar concentrations.
- Time: measurements within two to five minutes.
- Size range: suited to large molecules above 40 kDa.
- Concentration: a microfluidic dilution add-on is described as raising the upper concentration limit from the nanomolar to the micromolar range.
- Minor species: the article states that species making up less than one percent of the molecules in a sample can be detected, with contaminants detectable down to picomolar concentrations.
The same article describes a related macro mass photometry format for larger particles such as adenovirus and lentivirus.
How it compares with related techniques
Lab Manager frames mass photometry against methods labs already use.
| Question | Technique named in the article | Stated difference |
|---|---|---|
| Oligomeric state (monomer, dimer, tetramer) | Analytical ultracentrifugation | Analytical ultracentrifugation needs more sample and more time. |
| Antibody aggregation and fragmentation | SEC-MALS | SEC-MALS is population-averaged; mass photometry counts single molecules. |
| Binding stoichiometry and KD | Mass photometry, at equilibrium | Species counts at equilibrium give stoichiometry and an equilibrium dissociation constant. |
| AAV empty, full and partial capsids | Mass photometry | Capsid populations separate by mass. |
For other approaches to mass and binding measurements, see CASRAI’s guides on what a mass spectrometer is, resolving power and mass accuracy in high-resolution mass spectrometry and calculating KD from surface plasmon resonance binding kinetics.
Where it matters for labs
The sourced uses cluster around characterising a protein or capsid preparation before or during downstream work:
- Purity and homogeneity checks. Single-molecule counting shows sub-populations that an averaged readout would blur, which is useful after a purification step such as those covered in the protein purification guide.
- Oligomerization and complex assembly. Peaks at distinct masses indicate which assemblies are present and in what proportion.
- Antibody and AAV quality questions. Aggregates, fragments and empty versus full capsids are among the examples the trade article describes. For containment questions around AAV work, see the AAV biosafety level guide.
A checklist for reading a mass histogram
- Identify each peak and the mass it corresponds to; each peak is a species present in the sample.
- Compare peak masses with the masses expected for monomer, oligomers or complex partners.
- Check for small populations: the method is described as detecting species below one percent of molecules.
- Note whether any species of interest falls under about 40 kDa, the lower end of the range the trade article describes as suited.
- Record the working concentration, since the article describes low nanomolar sample concentrations as the standard range.
Common misunderstandings
- “It needs labels or tags.” It does not. Refeyn describes it as label-free and in solution.
- “The name means it only measures by mass spectrometry.” The 2018 paper named its approach interferometric scattering mass spectrometry, but the readout it describes is interferometric scattering microscopy of single molecules in solution.
- “It gives an average mass.” It reports counts per mass, so each species in a mixture has its own peak.
- “It works for any molecule.” The trade article describes it as suited to large molecules above 40 kDa.
FAQ
Does mass photometry need labels?
No. It measures unlabelled molecules in their native state in solution.
How much sample does it need?
Lab Manager describes 5 to 20 µL of sample at low nanomolar concentrations.
How fast is a measurement?
The same article describes measurements within two to five minutes.
What size of molecule can it measure?
It is described as suited to large molecules above 40 kDa, with a macro format for larger particles such as adenovirus and lentivirus.
What can it tell me about a protein sample?
Purity and homogeneity, oligomeric state, complex assembly and biomolecular interactions, as listed by Refeyn.
Sources
- Refeyn, “About mass photometry”, https://refeyn.com/about-mass-photometry, checked 2026-10-29.
- Lab Manager, “Harnessing the Power of Mass Photometry for Protein Characterization”, https://www.labmanager.com/harnessing-the-power-of-mass-photometry-for-protein-characterization-32363, checked 2026-10-29.
- Young G, et al. “Quantitative mass imaging of single biological macromolecules”, Science 360(6387):423-427, 2018, DOI https://doi.org/10.1126/science.aar5839, PMID 29700264, abstract checked 2026-10-29.
