CrystalsFirst

Too Many Tiny Crystals — Nucleation Control

Sometimes you get showered with micro-crystals or heavy precipitate. This often means conditions are too supersaturated, causing excessive nucleation.

The goal is to generate as few nuclei as possible to grow larger crystals. To achieve this, you can decrease the protein or precipitant concentration, or use a larger drop  slowing down equilibration.

Another trick is microseeding into conditions which don’t nucleate spontaneously – leading to a focus on the growth phase instead of the nucleation phase.  Additionally, by using a  dilution series of the  seed stock, it is possible to precisely adjust the  number of introduced pre-formed nuclei (seeds) which directly affects the final number and size of the grown crystals. This can allow a few crystals to outgrow the rest. Additives or detergents might help by reducing non-specific nucleation as well.

In short, gentle tinkering to dial back nucleation can convert “too many tiny crystals” into a few sizable ones.

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