Nanofluidic chips for reproducible cryo-EM sample preparation with picoliter sample volumes
Developing a nanofluidic chip for cryo-EM to enhance sample preparation, reduce consumption, and enable time-resolved imaging for drug design applications.
Projectdetails
Introduction
Cryogenic transmission electron microscopy (cryo-EM) is a technique for high-resolution imaging of radiation-sensitive biological macromolecules under near-native conditions.
Sample Preparation Techniques
Cryo-EM sample preparation techniques rely on rapid cooling of an aqueous suspension of biological macromolecules to obtain a thin layer of amorphous ice containing the solute.
Challenges in Current Implementations
Problems associated with current implementations are considered a major bottleneck to realizing the full potential of cryo-EM:
- Excessive sample consumption
- Difficulty in reproducibly obtaining ice conditions suitable for high-resolution imaging
- Extensive contact of solute molecules with a large air-water interface
These issues result in only a small fraction of the imaged molecules contributing useful information for the final 3D reconstruction.
Time Resolution Limitations
Poor time resolution of these methods furthermore precludes the visualization of dynamic structural changes that provide critical biological insight.
Proposed Solution
In our laboratory, we have developed technology to design nanofluidic MEMS devices suitable for cryo-EM imaging. We propose to explore product development of a nanofluidic chip for reproducible sample preparation with picoliter volumes.
Nanofluidic Chip Design
The sample is contained in nanochannels formed between membranes of an electron-transparent material, thereby controlling ice thickness and avoiding the formation of an air-water interface.
Advantages of the New Method
This method has all features to push cryo-EM to new frontiers:
- Requires minute amounts of sample
- Robustly provides uniform and customizable thickness gradients across the sampling area
- Time resolution that is limited only by the vitrification process itself
Future Opportunities
Our CryoChip will provide entirely new opportunities for time-resolved cryo-EM imaging and high-throughput applications in structure-based drug design for the pharmaceutical industry.
Collaboration with Industry
We will liaise with an industrial partner experienced in MEMS probe fabrication to explore process optimization and the viability of larger-scale production.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 150.000 |
Totale projectbegroting | € 150.000 |
Tijdlijn
Startdatum | 1-5-2022 |
Einddatum | 31-10-2023 |
Subsidiejaar | 2022 |
Partners & Locaties
Projectpartners
- TECHNISCHE UNIVERSITEIT DELFTpenvoerder
Land(en)
Geen landeninformatie beschikbaar
Vergelijkbare projecten binnen European Research Council
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
Making time-resolved cryo-EM available for the community of structural biologists: validate, improve, deriskThis project aims to develop and commercialize a novel time-resolved cryo-EM sample preparation method to enhance protein structure analysis and accessibility for users. | ERC Proof of... | € 150.000 | 2024 | Details |
4D scanning transmission electron microscopy for structural biologyThis project aims to develop advanced 4D-BioSTEM methodologies for cryo-EM to enhance contrast and resolution, enabling structure determination of small proteins and complex biological samples. | ERC Synergy ... | € 7.489.397 | 2024 | Details |
Streamlining structural biology: Developing a high-throughput cloud-based cryo-electron tomography platformDevelop a cloud-based workflow for automated high-throughput cryo-electron tomography data analysis to democratize access and reduce processing time, enhancing molecular research. | ERC Proof of... | € 150.000 | 2023 | Details |
Phase Contrast STEM for Cryo-EMThis project aims to enhance cryo-electron tomography in biology using high-resolution scanning transmission EM, improving imaging quality and enabling new insights into cellular structures. | ERC Advanced... | € 2.499.987 | 2022 | Details |
Dosimetry of Ultra-High Dose-Rate Electron Beams at Solid-Water Interfaces in Electron Microscopy: A Key Advance in Hydrated Samples ResearchThis project aims to develop novel instrumentation to study radiolytic chemistry in electron microscopy, enhancing understanding of water-solid interfaces and mitigating electron-beam effects. | ERC Consolid... | € 2.130.686 | 2024 | Details |
Making time-resolved cryo-EM available for the community of structural biologists: validate, improve, derisk
This project aims to develop and commercialize a novel time-resolved cryo-EM sample preparation method to enhance protein structure analysis and accessibility for users.
4D scanning transmission electron microscopy for structural biology
This project aims to develop advanced 4D-BioSTEM methodologies for cryo-EM to enhance contrast and resolution, enabling structure determination of small proteins and complex biological samples.
Streamlining structural biology: Developing a high-throughput cloud-based cryo-electron tomography platform
Develop a cloud-based workflow for automated high-throughput cryo-electron tomography data analysis to democratize access and reduce processing time, enhancing molecular research.
Phase Contrast STEM for Cryo-EM
This project aims to enhance cryo-electron tomography in biology using high-resolution scanning transmission EM, improving imaging quality and enabling new insights into cellular structures.
Dosimetry of Ultra-High Dose-Rate Electron Beams at Solid-Water Interfaces in Electron Microscopy: A Key Advance in Hydrated Samples Research
This project aims to develop novel instrumentation to study radiolytic chemistry in electron microscopy, enhancing understanding of water-solid interfaces and mitigating electron-beam effects.
Vergelijkbare projecten uit andere regelingen
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
CryoGridDENSsolutions en CryoSol-World ontwikkelen een innovatieve sample carrier voor Cryo-EM om de 3D-structuur van eiwitten beter te visualiseren en de toepassing in de farmaceutische industrie te versnellen. | Mkb-innovati... | € 332.080 | 2023 | Details |
Cryogene nanopositionerHet project onderzoekt de haalbaarheid en marktpotentieel van een innovatieve nanopositioner voor nanotechnologie en quantumtechnologie bij lage temperaturen. | Mkb-innovati... | € 20.000 | 2021 | Details |
AdDitive mAnufacturing Microfluidica – ADAMPimBio B.V. ontwikkelt kosteneffectieve, klantspecifieke microfluïdische chips voor biotechnologie en gezondheidszorg om onderzoek te versnellen. | Mkb-innovati... | € 20.000 | 2020 | Details |
Een polymere microgestructureerde nanowellchip voor de analyse van individuele cellen op basis van microfabricage met behulp van 3D-printtechnologieHet project ontwikkelt betaalbare, op maat gemaakte micro-3D-geprinte chips voor single-cell analyses ter verbetering van kankerdiagnostiek en gepersonaliseerde therapieën. | Mkb-innovati... | € 167.760 | 2023 | Details |
NanoElectroMechanical Infrared Light for Industrial and Environmental SensingDeveloping the NEMILIE uncooled IR sensor to achieve market readiness, offering high sensitivity at room temperature for diverse applications without the need for cryogenic cooling. | EIC Transition | € 2.223.128 | 2022 | Details |
CryoGrid
DENSsolutions en CryoSol-World ontwikkelen een innovatieve sample carrier voor Cryo-EM om de 3D-structuur van eiwitten beter te visualiseren en de toepassing in de farmaceutische industrie te versnellen.
Cryogene nanopositioner
Het project onderzoekt de haalbaarheid en marktpotentieel van een innovatieve nanopositioner voor nanotechnologie en quantumtechnologie bij lage temperaturen.
AdDitive mAnufacturing Microfluidica – ADAM
PimBio B.V. ontwikkelt kosteneffectieve, klantspecifieke microfluïdische chips voor biotechnologie en gezondheidszorg om onderzoek te versnellen.
Een polymere microgestructureerde nanowellchip voor de analyse van individuele cellen op basis van microfabricage met behulp van 3D-printtechnologie
Het project ontwikkelt betaalbare, op maat gemaakte micro-3D-geprinte chips voor single-cell analyses ter verbetering van kankerdiagnostiek en gepersonaliseerde therapieën.
NanoElectroMechanical Infrared Light for Industrial and Environmental Sensing
Developing the NEMILIE uncooled IR sensor to achieve market readiness, offering high sensitivity at room temperature for diverse applications without the need for cryogenic cooling.