Cryo-HIM-SIMS on the npSCOPE: Correlative Topographic, Transmitted and SIMS Imaging at Cryogenic Temperatures

Area of Science:

• Materials Science
• Microscopy
• Analytical Chemistry

Background:

• Multimodal helium ion microscopy (HIM) and secondary ion mass spectrometry (SIMS) offer nanoscale spatial imaging and chemical analysis.
• Cryogenic temperatures are crucial for analyzing beam-sensitive samples, preventing artifacts from sample preparation and beam damage.
• Existing methods struggle with preserving the native state of frozen-hydrated and beam-sensitive specimens.

Purpose of the Study:

• To develop and validate a cryogenically operated multimodal HIM system for nanoscale imaging and chemical analysis.
• To enable correlative topographic, volumetric, and chemical imaging under cryogenic conditions.
• To demonstrate the system's capability for analyzing beam-sensitive and frozen-hydrated samples with reduced artifacts.

Main Methods:

• Retrofitting a gas field ion source HIM (npSCOPE) with a liquid nitrogen-cooled chamber and cryo-sample stage.
• Implementing a cryo-sample transfer system and humidity-controlled cryo-glovebox for handling frozen-hydrated samples.
• Utilizing three detection modalities: secondary electron (SE) imaging, secondary ion mass spectrometry (SIMS), and scanning transmission ion microscopy (STIM).

Main Results:

• The cryo-setup maintained stable conditions (< -139 °C) for over 36 hours without significant ice buildup or edge effects.
• Cryo-SE imaging showed reduced beam-induced modification in silica-coated gold nanoparticles.
• Cryo-STIM imaging on gold foil demonstrated a 34% average improvement in ion transmission signal intensity compared to room temperature.
• Successful correlative cryo-analysis was achieved on cryo-lamellae of plunge-frozen cells prepared by cryo-focused ion beam milling.

Conclusions:

• Correlative cryo-ion-beam imaging and analysis provides a powerful nanoscale solution for multimodal investigations.
• The developed system effectively minimizes artifacts and beam damage in beam-sensitive materials.
• This approach is promising for studying close-to-native biological specimens and other sensitive materials at the nanoscale.