Amorphous aggregates with a very wide size distribution play a central role in crystal nucleation

There is mounting evidence that crystal nucleation from supersaturated solution involves the formation and reor-ganisation of pre-nucleation clusters contradicting classical nucleation theory. Here, a wide range of amino acids and peptides is investigated using light scattering, mass spectrometry, and in-situ terahertz Raman spectroscopy to demonstrate that the presence of amorphous aggregates with a wide range of sizes is a general phenomenon in supersaturated solutions. Additionally, these amorphous aggregates act as intermediates for laser-induced crystal nucleation. These observations are inconsistent not only with classical nucleation theory, but also non-classical theories involving liquid-liquid phase separation, requiring a new approach.