NativeSynapt – Native Electrospray made easy

Overcoming the limitations of standard MS instrumentation in the analysis of large protein structures has been the focus of our efforts over the past decade. By working together closely with leading academic groups, we learnt how to get the best out of the mass spectrometer. The result is an instrument which allows researchers to unleash the full capacity of the Synapt in the analysis of intact proteins and complexes by native electrospray mass spectrometry:

Antibody analysis
Antigen-Antibody interaction studies, stoichiometry, affinity studies
Antibody PTM analysis
Protein Complexes, protein-protein interactions
Virus capsids composition analysis

Turning the Synapt into a Native Electrospray MS platform

The interest in MS of large biomolecules and biomolecular complexes has significantly increased in the past years as more and more pharmaceuticals are either new biological entities (NBE) or biosimilars/biobetters.

The characterization of their behaviour is critical to understand their activity. Complex formation can lead to inactivity or even toxic effects.

For vaccine development, the analysis of AAV’s/VLP’s became a huge field of application in recent years. The characterization of the virus or virus-like capsids is critical to assess effects in immunization as well as adverse effects.

Making it work better

By careful consideration of the conditions that exist in the consecutive sections of the instrument, the performance of the Synapt for large ions can be improved considerably by changing the characteristics of the ion optical elements.

In particular

we optimized the ion generation and transfer by developing a new nanospray ion source with significantly reduced fringe fields compared to the original Waters ion source

we optimized the vacuum system, vacuum pressures and gas flow inside the system to improve desolvation and ion transfer

With a detection mass range up to 100.000 m/z and the Synapts ion mobility capability it is the ideal system for the characterization of very large complexes (e.g. virus particles or AAV’s) and complexes which change their conformation upon formation of ligand binding. The lower resolution of TOF systems in comparison to Orbitraps is not a restriction for these applications as commonly only average mass data is acquired anyway and an instrument resolution of only 10.000 would be more than enough for this.

For older generation QTOF systems (e.g. Ultima) we lowered the potential on the backend to increase the collision voltage range for more efficient fragmentation of very large ions such as e.g. GroEL (800 kDa) or virus capsids (2-10 MDa)

No compromise

All functionality of the original instrument is available on the NativeSynapt. Simply choose between modes and analyze your samples. Soft conditions for preservation of complexes, high energy dissociation, ion Mobility – it’s all possible!

Another beauty of MS Vision’s NativeSynapt upgrade is that it still is a Synapt HRMS system from the control perspective. With all the software you had before. No changes in data format or data processing. Whatever you used before, you can still use after the upgrade. Whether you use BiopharmaLynx, Protein Metrics’ Byosphere or other software, you can still use this as before without compromise.

At MS Vision we also recommend, in particular for academic users, the popular free UniDec software suite for mass deconvolution and ion mobility analysis.

Peer-reviewed publications using NativeSynapt

P. Lill et al., “Towards the molecular architecture of the peroxisomal receptor docking complex”, Proc. Natl. Acad. Sci. USA (2020), DOI: 10.1073/pnas.2009502117
F. Drepper et al., “A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications”, J. Biol. Chem. (2020), DOI: 10.1074/jbc.RA120.015882
M. Saluri et al., “A “grappling hook” interaction connects self-assembly and chaperone activity of Nucleophosmin 1”, PNAS Nexus (2023), 2, 1-9; https://doi.org/10.1093/pnasnexus/pgac303; Supplemental information
C. Sahin et al., “Mass Spectrometry of RNA-Binding Proteins during Liquid−Liquid Phase Separation Reveals Distinct Assembly Mechanisms and Droplet Architectures”, J. Am. Chem. Soc. 2023, 145, 10659−10668; https://doi.org/10.1021/jacs.3c00932; Supplemental information
D. Lama et al., “A druggable conformational switch in the c-MYC transactivation domain”, Nature Communications ( 2024) 15:1865; https://doi.org/10.1038/s41467-024-45826-7
L.J. Persson et al., “High-Performance Molecular Dynamics Simulations for Native Mass Spectrometry of Large Protein Complexes with the Fast Multipole Method”, Analytical Chemistry ( 2024) 96, 15023-15030; https://doi.org/10.1038/s41467-024-45826-7
F.M. Dijkema et al., “A suicidal and extensively disordered luciferase with a bright luminescence”, Protein Science ( 2024); https://doi.org/10.1038/s41467-024-45826-7
S. Nishio et al., “ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat”, Cell (2024), 187, 1440-1459; https://doi.org/10.1038/s41467-024-45826-7
A. Haase, C. Arlt, A. Sinz, R.G. Sawer, “Evidence the Isc iron–sulfur cluster biogenesis machinery is the source of iron for [NiFe]‑cofactor biosynthesis in Escherichia coli”, Nature Scientific Reports (2024) 14:3026; https://doi.org/10.1038/s41598-024-53745-2

Upgrade or full instrument?

Whether you want to have your own Synapt upgraded or need a complete instrument, MS Vision has the solution. We offer full support by our highly skilled engineers so you can concentrate on running your samples.

Native Mass Spectrometry is in demand and the Waters Q-Tof type instruments and Synapt type instruments can all be upgraded by MS Vision for Native MS applications. MS Vision have a stock of complete instruments ready for the upgrade of your choice.

It’s up to you to decide for a 8 or 32 kDa quad upgrade! Do you require all the vacuum modifications and gas control additions as descripted in our article being controlled by Mass Flow controllers or for budget reasons choose the manual gas controllers? Based upon your request and budget we can build your system as you wish.

The system will be completely refurbished and is better than new!

A new PC to drive the entire system and to help you with your analysis using the complete suite of MassLynx software Waters will be supplied with the instrument. The system will be installed in your laboratory and will meet specifications before it will be transferred to you. After this we will give a first training followed by a advanced training course a few months later are standard.

The guarantee is 12 months on the entire system, not only on the upgrade parts! Following the guarantee service contracts from a Bronze type, PM only to full cover Platinum type are available.We guarantee that all parts required to keep your system running are available for at least 7 years following installation and acceptance.