What Is MicroED?
MicroED (Micro-crystal Electron Diffraction) is a technique that uses the electron beam of a cryo-EM to collect diffraction data from microcrystals. Because electrons interact much more strongly with matter than X-rays, crystals that are too small for X-ray diffraction (even <1μm) can produce high-quality MicroED data.
MicroED vs X-ray Crystallography
| Feature | MicroED | X-ray Crystallography |
|---|---|---|
| Crystal size | 0.1-10 μm | 50-500 μm |
| Resolution | 0.6-1.5Å | 0.8-2.0Å |
| Sample needed | Micrograms | Milligrams |
| Time | Hours to days | Days to weeks |
| Polymorphs | Can distinguish | May miss |
Applications in Drug Discovery
1. Drug Compound Structures
Determine the 3D structure of API (active pharmaceutical ingredients) for regulatory filings.
2. Polymorph Identification
Different crystal forms of the same drug can have vastly different bioavailability. MicroED can identify and characterize polymorphs from tiny crystals.
3. Natural Product Structure Elucidation
Many natural products form only microcrystals. MicroED can solve structures that resist X-ray analysis.
4. Co-crystal and Salt Screening
Quickly characterize co-crystals and salts for formulation development.
How It Works at Shuimu
- Sample delivery: Send microcrystals in mother liquor or dried
- Grid preparation: Crystals are dispersed on cryo-EM grids
- Data collection: Continuous rotation electron diffraction on 300kV microscope
- Structure solution: Direct methods or molecular replacement
- Delivery: Atomic model, validation report, and CIF file
Shuimu has solved MicroED structures at resolutions as high as 0.65Å, including drug compounds, natural products, and proteinase K.
Learn more about our MicroED service or contact us to discuss your small molecule project.