News Release

Visualizing diffusive dynamics beyond tracking limit with standard optical microscope

Evaluating the spatio-temporal distribution of diffusion coefficients for high-concentration Brownian particles without fluorescent labeling nor tracking them from microscopy movie data analysis based on the statistical physics

Peer-Reviewed Publication

Tokyo University of Agriculture and Technology

Graphical Abstract of This Research

image: Visualization of crystallization before it is actually visible by live imaging view more 

Credit: FIGURE ADAPTED FROM The Journal of Physical Chemistry Letters, 2019 10 (23), 7452-7457. COPYRIGHT © 2019 American Chemical Society.

The collaborative team including an expert of statistical physics from mechanical engineering science (Prof. Hanasaki) and physical chemists (Prof. Sugiyama and Prof. Yoshikawa) developed a new approach that can detect a sign of crystallization in solution before crystals were actually formed. These scientists used the optical trapping to induce crystals in solution at a location where laser was focused. Then a process of crystallization was live recorded through optical microscopy. Whereas the visual inspection tells nothing before crystal nucleation, the analysis reveals the collective motion of molecular clusters from the same movie data from long before the nucleation event.

Their findings were published in The Journal of Physical Chemistry Letters on Nov 21st, 2019.

In general, microscopic observation of materials is carried out by scanning or transmission electron microscopy (SEM or TEM) or scanning probe microscopy (SPM). These microscopes require dry samples and only surface of these samples can be viewed. In contrast, wet materials such as biological cells can be observed by optical microscopy with lower resolution compared to that of SEM, TEM, and SPM. It is, however, difficult to visualize dynamics of highly concentrated molecular clusters in solution by these microscopes.

At the beginning of crystallization, it is known that molecules in solution form clusters with sizes far below the diffraction limit before the crystal nucleation. The cluster means a precursor of crystal, followed by the crystal nucleation, which takes place where sufficient concentration of molecular crystal precursors is reached.

"In 2018, we demonstrated a new methodology based on the algorithm that I had developed and coined the name 'particle image diffusometry' (PID), which allows us to see diffusion coefficient 'field' from the movie data obtained from the standard inverted optical microscope with white light source," said Hanasaki, the first author of the paper and an associate professor in the Institute of Engineering, Tokyo University of Agriculture and Technology (TUAT), Japan. "This research was the first 'field' application of the PID, and we non-invasively observed the dynamics of crystal precursors in solution."

"The PID revealed the spatio-temporal dynamics of molecular crystal precursors before the nucleation event, based on the principle of statistical mechanics, although the visual inspection of the microscopy movie tells us nothing before nucleation," adds Hanasaki. Their results indicate that the precursors have the viscosities similar to that of honey, indicating that the material state just before the crystallization is indeed between the typical liquid and solid. "We expect that this research, the first visualization without fluorescence labelling nor tracking during crystallization, opens a new avenue for soft material handling in general. In addition, understanding of the crystal nucleation is important not only for the fundamental physics in terms of phase transition, but also for the pharmaceutical developments, where the control of crystallization protocol is required, coping with the molecular diversity," explains Hanasaki.


This work was partly supported by JSPS KAKENHI Grant Numbers 17H05463 and JP16H06507 in Scientific Research on Innovative Areas "Nano-Material Optical-Manipulation"; Nos. 19KK0128 and 19H02613, Ministry of Science and Technology (MOST) in Taiwan (107-2113-M-009-002-); and Center for Emergent Functional Matter Science of National Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.

For more information about the Hanasaki laboratory, please visit

Original publication: Spatiotemporal Dynamics of Laser-Induced Molecular Crystal Precursors Visualized by Particle Image Diffusometry Itsuo Hanasaki, Kazuki Okano, Hiroshi Y. Yoshikawa, and Teruki Sugiyama The Journal of Physical Chemistry Letters, 2019 10 (23), 7452-7457 DOI: 10.1021/acs.jpclett.9b02571

About Tokyo University of Agriculture and Technology (TUAT): TUAT is a distinguished university in Japan dedicated to science and technology. TUAT focuses on agriculture and engineering that form the foundation of industry, and promotes education and research fields that incorporate them. Boasting a history of over 140 years since our founding in 1874, TUAT continues to boldly take on new challenges and steadily promote fields. With high ethics, TUAT fulfills social responsibility in the capacity of transmitting science and technology information towards the construction of a sustainable society where both human beings and nature can thrive in a symbiotic relationship. For more information, please visit

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