[3dem] MicroED on small molecule

[Takanori Nakane]

Hi,

I am glad to see a MicroED question on this mailing list.

To answer your question, I need to know the size of your crystals,
the type of aggregation (e.g. layered plates, aggregates
of small blocks etc) and the particle density on a grid.
Can you show me a low-magnification image (e.g. x2600) of
your crystals on a grid?

I also want to know your beam size (or the effective
data collection area if you use an SA aperture).

In general, it is acceptable to have a few crystals
in the beam. Modern data processing programs have no problems
indexing diffraction images containing multiple lattices.
The unit cell of small molecule crystals is small and we
don't have many overlapping spots.

With automated data collection, I routinely collect
100 - 300 crystals per grid and select best
(high resolution, less overlaps, highly isomorphic) crystals
post-hoc.

You can make the effective data collection area smaller
with a SA aperture but crystals often go out of the area
at high tilt unless the eucentric height is very accurate and the
goniometer is stable. So I use beam with a diameter of ~ 1.6 um
without a SA aperture.

If *really* necessary, several tricks to de-clump crystals are:

- suspend in a poor solvent and apply ultrasonic for a few seconds
   (you can also remove large aggregates by weak centrifugation)
- grind between two glass slides
- grid with a mortar and pestle

However, such physical interventions often degrade the crystal quality
and require optimization for each sample.
Thus, I avoid these as much as possible.

Best regards,

Takanori Nakane

On 2026/01/16 3:37, Yu, Xiaodi [JRDUS] via 3dem wrote:
> Hi everyone,
> 
> I’d like to consult MicroED experts about a small‑molecule sample: the 
> powder contains diffracting microcrystals, but they stick together and 
> make data collection difficult. Does anyone have recommended approaches 
> or tips to prevent clumping and improve data collection?
> 
> Thanks in advance,
> Xiaodi
> 
> 
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