Back to BPS: Celebrating four years of mass photometry

Four years ago, at the Biophysical Society’s Annual Meeting 2018 in San Francisco, an early mass photometer made its first public appearance, when a University of Oxford team led by Philipp Kukura and Daniel Cole brought a prototype to demonstrate live in the BPS exhibition hall.


Image source : Twitter

The prototype, built in just four months, showed what mass photometry was capable of. However, the team had not yet published their landmark paper that would show it is possible to weigh molecules using light scattering. They knew the technology could fundamentally alter biomolecular analysis, but only if other scientists were willing to give it a try.


Interest in the new technology at the 2018 BPS meeting was tremendous. Building on that momentum, the team launched the spin-off company first known as Arago Biosciences in June 2018. The first mass photometry instruments were shipped to customers shortly after, and in February 2019, the company was renamed Refeyn.


Mass photometry has come a long way since then. To explore this, we analysed the mass photometry papers that have been published in peer-reviewed journals. Here’s what we found.



There are more peer-reviewed publications using mass photometry coming out every year – there’s now at least one per week (and yes, we read them all!).


And there are now over 100 papers featuring mass photometry! A publication century in just four years – we are very proud that mass photometry has been making such an impact.


Number of scientific publications featuring mass photometry, based on data collected by Refeyn between 2018 – 2021.

Image : Number of scientific publications featuring mass photometry, based on data collected by Refeyn between 2018 – 2021.


 

The researchers using mass photometry are publishing in top scientific journals.


Here, we show the journals with the most mass photometry publications. Together, this set accounts for close to 40% of the total mass photometry publications.



Image: Analysis of scientific journals in which mass photometry publications appeared most frequently, based on data collected by Refeyn between 2018 – 2021.


 

Clearly, quite a few researchers are realising how useful mass photometry is, but what are they using it for?


Researchers are using mass photometry for a wide variety of applications, but the most frequent so far are: analysis of complex formation and stoichiometry, sample heterogeneity, and oligomeric state.



Image: Primary application areas for mass photometry publications, based on data collected and categorised by Refeyn between 2018 – 2022.


 

Good science gets noticed – and cited.


Mass photometry publications are attracting lots of citations. Here are the top 10 most widely cited publications featuring mass photometry.



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.

This paper introduced mass photometry, showing that interferometric scattering microscopy could be used to measure the mass of single biomolecules with high accuracy, resolution and precision.



A. D. Malay et al., ‘An ultra-stable gold-coordinated protein cage displaying reversible assembly’, Nature, vol. 569, no. 7756, pp. 438–442, May 2019, doi: 10.1038/s41586-019-1185-4.

Mass photometry enabled kinetic tracking of the formation of a cage-like protein structure arranged in a way that had not been previously seen in molecular systems.


A. Sonn-Segev et al., Quantifying the heterogeneity of macromolecular machines by mass photometry’, Nat Commun, vol. 11, no. 1, p. 1772, Apr. 2020, doi: 10.1038/s41467-020-15642-w.

This paper showed that mass photometry provides an ideal way to characterise sample purity prior to further analyses, proving rapid results with minimal sample.


F. Soltermann et al., ‘Quantifying Protein–Protein Interactions by Molecular Counting with Mass Photometry’, Angewandte Chemie International Edition, vol. 59, no. 27, pp. 10774–10779, 2020, doi: 10.1002/anie.202001578.

A demonstration that mass photometry offers a way to measure the interaction kinetics and binding affinities of unlabelled biomolecules.



R. F. Garmann, A. M. Goldfain, and V. N. Manoharan, ‘Measurements of the self-assembly kinetics of individual viral capsids around their RNA genome’, PNAS, vol. 116, no. 45, pp. 22485–22490, Nov. 2019, doi: 10.1073/pnas.1909223116.

Mass photometry was used to measure the assembly kinetics of bacteriophage capsids, helping resolve the decades-old question of how individual capsids self-assemble.


K. Häußermann et al, ‘Dissecting FOXP2 Oligomerization and DNA Binding’, Angew Chem Int Ed Engl. 2019 Jun 3;58(23):7662-7667. doi: 10.1002/anie.201901734.

Mass photometry was used to quantify the interactions of human FOXP2 with itself, and to determine the different oligomeric states present in its different variants



D. Wu, G. Piszczek, ‘Measuring the affinity of protein-protein interactions on a single-molecule level by mass photometry’, Anal Biochem. 2020 Mar 1;592:113575. doi: 10.1016/j.ab.2020.113575.

A study in which mass photometry was used to determine the affinities of mono- and multivalent protein-protein interactions.


S. Tamara, V. Franc, A. J. R. Heck, ‘A wealth of genotype-specific proteoforms fine-tunes hemoglobin scavenging by haptoglobin’, Proceedings of the National Academy of Sciences Jul 2020, 117 (27) 15554-15564; DOI: 10.1073/pnas.2002483117.

In this publication, mass photometry was used to investigate the differences in binding stoichiometry among the Hp-Hb complexes formed, and to investigate the minor variations in binding affinities between Hp and Hb between Hp genotypes.


J. Brun et al, ‘Assessing Antigen Structural Integrity through Glycosylation Analysis of the SARS-CoV-2 Viral Spike’, ACS Central Science 2021 7 (4), 586-593, doi: 10.1021/acscentsci.1c00058.

Mass photometry was used to show how site-specific glycosylation differs between virus-derived, wild-type, non-stabilised spikes and commonly used recombinant, engineered spikes.


Y. Li, W.B. Struwe, P. Kukura, ‘Single molecule mass photometry of nucleic acids’, Nucleic Acids Research, Volume 48, Issue 17, 25 September 2020, Page e97, https://doi.org/10.1093/nar/gkaa632

In this publication, mass photometry used to measure the molecular weight of nucleic acids.


 

But, peer-reviewed journals are not the only medium where people talk about mass photometry!


Although the below mentions are not from our publication analysis, we love hearing about (and seeing!) how mass photometry instruments are being used. Keep those tweets coming…



 


Further Resources


To learn more about the use of mass photometry in SARS-CoV-2 research, we recommend:


Blog: How does mass photometry work?

This blog post outlines both the science behind mass photometry and why it is such a useful technology.


Webinar: Measuring Molecules with Light

Refeyn co-founder, Prof. Philipp Kukura, explains how mass photometry can transform biomolecular analysis, and discusses its strengths and limitations.


Live remote demo

If you are exploring mass photometry and would like to see the instrument or ask some questions, register for our live remote demos. During these demos, one of our mass photometry experts will show how to use the mass photometer on some samples and will be happy to answer any questions about the technology.

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