Cryo-EM, or cryogenic electron microscopy, is an analyses method which is used in the field of bio-research to analyze cells, bacteria and proteins. These samples are frozen to extreme low temperatures (-196 °C) to fixate the sample which makes it than compatible with electron microscope analyses.
The recent surge in interest in cryo TEM (Transmission Electron Microscopy) has given rise to new approaches in sample preparation. Complicated samples such as cells, bacteria and tissues must be thinned down, using a focused ion beam (FIB), before they can yield results in the cryo TEM. The need for such thin cryo specimen has given rise to a cryo correlative microscopy workflow to create cryo lamella. In this workflow, a fluorescence microscope (FM) is used to pinpoint a region of interest based on a fluorescent label present in the sample. The sample is subsequently brought to the FIB/SEM to be thinned, before being transferred to the TEM for the final imaging step.
This workflow has the potential to give great insight into protein structures within their natural environment. However, the workflow is currently highly complex with a low yield of good cryo lamella. Obtaining good results on such lamella is currently a slow, uncertain and laborious process.
Currently Demcon kryoz is developing a micro cryogenic cold stage which is optimized for the usage with FM/SEM/FIB analyses where it cryocools the bio-sample. One of the key requirements is that the cooling method should not add any significant drift or vibration to the setup. Demcon kryoz has developed various methods to suppress the thermal drift and vibration of the cryogenic microcooler.
The task within this project is to further analyze, design and optimize a setup to measure these vibration (<1 nm p2p @ 200 Hz @ 108 K) and drift levels (<5 nm min-1 @ 108 K). The setup should be able to measure these ranges of drift and vibration on the microcooler tip itself while it is at cryogenic temperatures.
Activities can include (depending on the time-frame):
- system analyses (modelling of thermal drift, vibration, mechanical stability, referencing, measuring methods, measurement apparatus capability, etc)
- measurement system optimization (requirement analyses, current design upgrade)
- upgrade measurement system realization: build the new setup and test
- validation and verification: check requirements of setup and verify cold-stage drift and vibration levels
Company profile DEMCON advanced mechatronics
Demcon kryoz offers both products and services in the field of cryogenics and thermal systems. We are a sub-division of the Demcon Group (over 600 employees), that delivers cryocoolers (mainly for cooling small non-dissipative devices or samples), develops (semi)customized cryocooling solutions (using our own microcooling technology or other cryocoolers including Stirling, Pulse-tube and cryostats) and provide services and advice to customers which require input on cryogenics or other thermal systems.
Additionally, we are active in the field of mechatronics, software, electronics and (high-tech) apparatus production and sales which all are part of Demcon’s core-competences. One of our market focus areas is life-sciences. More specific Cryo-EM applications.
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