A platform for retaining native morphology at sub-second time scales in cryogenic transmission electron microscopy

Area of Science:

• Materials Science
• Biophysics
• Analytical Chemistry

Background:

• Cryogenic transmission electron microscopy (cryo-TEM) is crucial for analyzing complex fluid morphology.
• Current sample preparation methods introduce artifacts due to high shear rates and limited time resolution.
• Non-specific adsorption further alters sample concentration, hindering accurate analysis.

Purpose of the Study:

• To develop a novel sample preparation device for cryo-TEM.
• To overcome limitations of existing methods, including shear-induced artifacts and poor temporal resolution.
• To enable the study of complex fluids in their native, solution state.

Main Methods:

• A new device utilizing capillary action for sample preparation was developed.
• A removal capillary parallel to the grid reduces shear and minimizes particulate adsorption.
• A deposition capillary perpendicular to the grid allows for precise, sub-second time-resolved deposition.

Main Results:

• The new device successfully minimized shear rates and non-specific adsorption.
• Sub-second time resolution was achieved for capturing dynamic processes.
• Model samples prepared with the device showed improved native morphology compared to current methods.
• The device demonstrated enhanced capabilities for sample preparation in cryo-TEM.

Conclusions:

• The developed capillary-action device significantly improves sample preparation for cryo-TEM.
• It overcomes critical limitations of existing methods, enabling artifact-free imaging.
• This innovation provides new possibilities for studying complex fluids and dynamic processes at high resolution.