MS SPIDOC · Project

Faster Protein Structure Imaging Without Crystals for Drug Discovery

healthPrototypeTRL 4Thin data (2/5)

Figuring out the 3D shape of a protein is like trying to photograph a tiny invisible object — and until now, you often had to grow it into a crystal first, which many proteins just refuse to do. This project built a system that shoots proteins one at a time into an ultra-powerful X-ray beam, already sorted by size and shape, and lined up so the camera gets a clean shot. Think of it like sorting M&Ms by color before photographing them, instead of dumping the whole bag and trying to figure it out later. The result: you need far less data to reconstruct the protein's shape, which means faster answers for anyone designing drugs or studying diseases.

By the numbers

EUR 3,730,000

EU funding for development of the X-MS-I system

consortium partners across 6 countries

industry partners including 2 SMEs involved in commercialization

total project deliverables completed

The business problem

What needed solving

Determining the 3D structure of proteins is essential for drug design, but many important protein targets refuse to form crystals — the standard requirement for X-ray structure determination. Even when imaging works, the enormous datasets needed for reconstruction create processing bottlenecks that slow down research timelines. Companies working on complex drug targets or therapeutic proteins waste months waiting for structural data that may never come.

The solution

What was built

The project built and installed a prototype X-MS-I system — a native mass spectrometry-based sample delivery device — at the European XFEL's SPB/SFX instrument. This system delivers mass-sorted, conformation-selected, and dipole-oriented protein complexes for single particle imaging, enabling structure determination without crystallization and from smaller datasets. A total of 13 deliverables were completed.

Audience

Who needs this

Pharmaceutical companies with crystallization-resistant drug targetsScientific instrument manufacturers expanding into structural biologyBiotech firms engineering therapeutic proteins or antibody complexesXFEL and synchrotron facilities upgrading their sample delivery capabilitiesContract research organizations offering protein structure determination services

Business applications

Who can put this to work

Pharmaceutical R&D

enterprise

Target: Drug discovery companies struggling with protein targets that resist crystallization

If you are a pharma company dealing with 'undruggable' protein targets that cannot be crystallized for traditional X-ray analysis — this project developed a mass spectrometry-based sample delivery system (X-MS-I) that images individual protein complexes without crystallization. It also captures transient conformational states, meaning you can see proteins mid-action, not just frozen in one pose. The consortium of 9 partners across 6 countries validated the prototype at the European XFEL facility.

Scientific Instrumentation

mid-size

Target: Manufacturers of mass spectrometry or X-ray imaging equipment

If you are an instrument manufacturer looking to expand into structural biology markets — this project created new mass spectrometry components and methods specifically designed for single particle imaging at X-ray free-electron laser facilities. The project explicitly aims to open new components and methods to the market. With 2 industry partners already in the 9-member consortium, commercialization pathways were built into the project from the start.

Biotech & Protein Engineering

any

Target: Biotech companies engineering therapeutic proteins or antibodies

If you are a biotech company that needs to verify how your engineered proteins fold and behave in real conditions — this project built a system that can image protein complex unfolding in real time. Instead of waiting weeks for crystallization and analysis, the X-MS-I system sorts proteins by mass and conformation before imaging, dramatically speeding up structure determination. The EUR 3,730,000 project delivered a working prototype installed at a world-class XFEL facility.

Frequently asked

Quick answers

What would it cost to access this technology?

The prototype is installed at the European XFEL facility, which operates as a user facility with beam-time allocation. Access costs depend on the facility's pricing model for industrial users. The project itself received EUR 3,730,000 in EU funding across 9 partners, so the underlying R&D investment was substantial.

Can this work at industrial scale for high-throughput screening?

The system was designed to speed up structural analysis by requiring much smaller datasets for reconstruction. However, it currently operates at a specialized XFEL facility, not in a standard lab. Scaling would require either more XFEL beam time or adaptation of the sample delivery system to other X-ray sources.

What is the IP situation and can we license this?

The project states that new components and methods will be opened to the market to strengthen European industry. With 2 industry partners and 2 SMEs in the consortium, commercial licensing pathways likely exist. Contact the coordinator at Leibniz-Institut für Virologie (Germany) for licensing terms.

How much faster is this compared to current methods?

The project objective states that orienting proteins along their dipole axis enables structural reconstruction from much smaller datasets, speeding up the analysis time tremendously. Exact speed-up factors are not specified in the available project data, but the reduction in required data volume is the key advantage.

Does this replace existing cryo-electron microscopy workflows?

It complements rather than replaces cryo-EM. The project notes that the data challenge is currently also a problem in electron microscopy. The X-MS-I approach offers advantages for proteins that resist crystallization and for capturing transient conformational states — areas where cryo-EM also faces limitations.

What was actually delivered and demonstrated?

The project delivered a working prototype: an X-MS-I experimental chamber installed at the SPB/SFX instrument at European XFEL. This is confirmed by the demo deliverable listing. A total of 13 deliverables were completed across the project.

Consortium

Who built it

The 9-partner consortium spans 6 countries (Germany, Greece, France, Netherlands, Sweden, UK) with a balanced mix: 4 universities, 2 research institutes, 2 industry partners, and 1 other organization. The 22% industry ratio and presence of 2 SMEs indicate some commercial orientation, though the consortium is predominantly academic. The coordinator is Leibniz-Institut für Virologie in Germany, a public research institute — meaning technology transfer would need to go through institutional licensing channels. The multi-country spread suggests broad European expertise but also means IP arrangements across 6 jurisdictions may add complexity for a commercial partner.

LEIBNIZ-INSTITUT FUR VIROLOGIECoordinator · DE
UNIVERSITE LYON 1 CLAUDE BERNARDparticipant · FR
THE UNIVERSITY OF MANCHESTERparticipant · UK
SPECTROMETRY VISION BVparticipant · NL
UPPSALA UNIVERSITETparticipant · SE
FASMATECH EPISTIMONIKI KAI TECHNOLOGIKI ANONYMI ETAIREIAparticipant · EL
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRSthirdparty · FR
UNIVERSITAET GREIFSWALDparticipant · DE
EUROPEAN X-RAY FREE-ELECTRON LASERFACILITY GMBHparticipant · DE

How to reach the team

Leibniz-Institut für Virologie, Germany — reach out to the structural biology or instrumentation group lead

Order a report on this consortium See LEIBNIZ-INSTITUT FUR VIROLOGIE profile →

Next steps

Talk to the team behind this work.

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