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Sample Requirements for Cryo-EM Epitope Mapping

Understand what is needed to initiate a cryo-EM study, and how quickly your sample can translate into decision-ready structural insights.
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What you need to get started

Most cryo-EM projects at ATEM can begin with standard purified biologics samples. Requirements are designed to minimize preparation effort while ensuring reliable structural analysis.

Antigen Requirements
  • Purified antigen or defined antigen identity. Alternative: antigen sequence can be provided — ATEM supports protein sourcing
  • Stable and homogeneous sample preferred
  • Contributes to total complex size (typical complex ≥ 65 kDa)
  • Compatible with antibody/binder complex formation
Antibody / Binder Requirements
  • Supported formats: IgG, Fab, scFv, VHH/nanobodies, peptides, aptamers
  • Typical amount: ≥ 0.5–1 mg per component
  • Typical concentration: ≥ 2 mg/mL
Tags and Modifications
  • Typically compatible: small affinity tags (e.g. His-tag, FLAG-tag)
  • Conditionally compatible: larger tags depending on target size and complex stability
  • Tags should not interfere with binding interface or structural integrity

Experimental conditions

Cryo-EM is compatible with a wide range of biologics formats and conditions, reducing the need for extensive sample manipulation.

Key Considerations

  • Buffer compatibility:
    Most standard biochemical buffers are suitable for vitrification (optimization available if required)
  • Complex formation:
    A stable antigen–binder interaction is required
  • Molecular behaviour:
    Samples should remain stable and well-dispersed during preparation
  • Complex size (typical):
    ≥ 65 kDa for reliable structural reconstruction

What you don't need

Cryo-EM removes many constraints associated with traditional structural methods.

  • Immobilization, Linkers or Conjugation
  • Deglycosylation or Mutation
  • Crystallization
  • Isotope Labelling
  • Digestion or Denaturing

What happens next

Every project starts with a short feasibility phase to confirm that your sample can generate meaningful structural data.

Pilot phase (~2 weeks):
  • Sample quality and stability assessment
  • Initial cryo-EM screening
  • Feasibility validation

You receive a clear recommendation on how to proceed toward structural analysis and decision-making.

1. Antibody Development
View antibody development workflow
2. LNP Development
EXPLORE LNP development workflow
3. Gene Therapy & AAV Vector Analysis
sEE GENE THERAPY & AAV ANALYSIS WORKFLOW

Not sure if your sample is suitable?

Most samples can be assessed quickly based on basic information.
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