Making time-resolved cryo-EM available for the community of structural biologists: validate, improve, derisk

Información del proyecto

trEM4all

Identificador del acuerdo de subvención: 101123392

DOI

10.3030/101123392

Proyecto cerrado

Fecha de la firma de la CE 8 Diciembre 2023

Fecha de inicio 1 Febrero 2024

Fecha de finalización 31 Julio 2025

Financiado con arreglo a

• European Research Council (ERC)

Coste total

Sin datos

Aportación de la UE

€ 150 000,00

Coordinado por

VIB VZW
Belgium

Periodic Reporting for period 1 - trEM4all (Making time-resolved cryo-EM available for the community of structural biologists: validate, improve, derisk)

Período documentado: 2024-02-01 hasta 2025-07-31

Resumen del contexto y de los objetivos generales del proyecto

Experimental determination of protein structures is central to molecular biology and drug development. Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology by enabling rapid structure determination of proteins vitrified in solution. However, current cryo-EM sample preparation methods limit the observation of dynamic processes and the use of low-yield or native samples.

To address these limitations, we developed two complementary microfluidics-based technologies:
- Time-resolved cryo-EM (trEM): enabling structural snapshots of proteins in action.
- Microfluidics-based Isolation for Sample Optimization (MISO): facilitating cryo-EM sample preparation from low-yield or native sources.

Both technologies were at TRL2 at project start and lacked commercial equivalents. The trEM4all project aimed to validate, improve, and derisk these innovations, exploring their broader dissemination and commercialization potential.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

- trEM Technology: Validated on two new protein classes, including membrane proteins. A new chip design was developed to prevent dye-induced protein damage, enabling high-resolution reconstructions of fragile complexes. A patent was filed for this improved design.
- MISO Technology: Originally developed under an ERC-CoG grant, MISO was integrated into trEM4all for business analysis and scalability studies. It reached TRL4 and attracted strong interest from pharmaceutical companies for its potential to streamline cryo-EM workflows.
- Scalability: Transitioned microfluidic chips from PDMS to thermoplastics using hot embossing, demonstrating feasibility for industrial production of both trEM and MISO chips.
- Commercial Interest: Engaged with cryo-EM manufacturers and pharma companies. While trEM was seen as promising but early-stage, MISO received strong interest for near-term applications. A roadmap for MISO MVP development was created, and additional funding secured to support its transition.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

- trEM: Achieved TRL3 with validated applications, improved chip design, and dedicated cryo-EM grid concepts (cGrids).
- MISO: Advanced to TRL4 with validated use cases and strong market traction. A spin-off roadmap and MVP development plan were created.
- Technology Transfer Needs: Further chip refinement, external lab testing, and demo device development are planned. Industrial partnerships and public funding are being pursued to reach TRL6.

Graphical abstract of the PoC project