May 10, 2024
Research Highlight

Deciphering How Crystals Form in Non-Classical Ways

Creating a comprehensive picture of non-classical nucleation of soft and organic materials from two decades of research

Graphic illustration of crystal formation

Over the past two decades, advancements have provided a clearer picture of the mechanisms of crystal assembly. This review highlights key breakthroughs in crystallization pathways of both soft and organic materials and emphasizes future research directions. The article is featured on the cover of the April issue of Nature Reviews Materials.

(Image by Cortland Johnson | Pacific Northwest National Laboratory)

The Science

Crystalline soft and organic materials have a wide range of applications, from pharmaceuticals to flexible electronics. Understanding exactly how they crystallize and form has historically been challenging due to the difficulty of observing these materials during assembly. Over two decades of research, significant advances have been made in theory and experiments to develop a more accurate picture of crystal assembly. This review identifies key breakthroughs in understanding the crystallization pathways of soft and organic materials, as well as highlighting important future directions for the field. In particular, the necessity of in situ measurements is emphasized.

The Impact

Soft and organic crystals are a diverse group of materials with connections to biological, environmental, and industrial processes. Understanding the details of their crystallization pathways is essential to developing the ability to controllably synthesize new materials and structures with targeted properties. This article offers a broad perspective on assembly of a range of materials, filling a need for a comprehensive review of the field.


While classical theories of how crystals form and grow have been long established for a range of materials, they provide an incomplete picture of crystallization. Many soft and organic materials form via non-classical pathways that lead to substantially different final crystal structures. Recent experimental advancements have enabled more accurate and in-depth analysis of these materials during and after formation. A new review article examines two decades of research on the non-classical formation pathways of soft and organic crystalline materials. It details the current theoretical understanding of how these materials form through non-classical pathways, including distinguishing the processes of nucleation and growth across models. Advances in experimental methods, including in-line scattering/spectroscopy detection, cryo microscopy, and in situ liquid-phase characterization, and their application to studying soft and organic crystalline materials are also discussed. These experimental techniques have provided strong evidence for non-classical crystallization pathways, leading to key breakthroughs in understanding these processes. However, the sole presence of a specific final product or intermediate does not prove that a material formed via a specific pathway. Thus, in situ techniques and kinetics measurements are essential to developing the detailed knowledge necessary to understand how these materials form.


James De Yoreo
Pacific Northwest National Laboratory


Review of biomacromolecules was supported by the Department of Energy (DOE) Office of Science (SC) Basic Energy Sciences (BES) program as part of the Energy Frontier Research Centers program: The Center for the Science of Synthesis Across Scales under Award DE-SC0019288 (FWP 72448 at Pacific Northwest National Laboratory). Review of reticular framework materials and small organic molecules was supported by the DOE SC BES Division of Materials Science and Engineering (MSE) Synthesis and Processing Sciences program under Award FWP 67554 at PNNL. Review of colloids and techniques was supported by the DOE SC BES MSE Biomolecular Materials program under Award FWP 65357 at PNNL. J.S.D. acknowledges a Washington Research Foundation Postdoctoral Fellowship.

Published: May 10, 2024

Du J. S., Y. Bae, J. J. De Yoreo. 2024. “Non-classical crystallization in soft and organic materials.” Nature Reviews Materials 9, 229-248 [DOI: 10.1038/s41578-023-00637-y]