A novel study by the Indian Institute of Technology (IIT) Hyderabad, the University of Hyderabad, Forschungszentrum Jülich GmbH, Jülich, Germany, and others has developed a method to produce clear microscopic images of liquids in real-time. The method addresses an important challenge in imaging liquids using Liquid Cell Transmission Electron Microscopy (LCTEM).
Liquid Cell Transmission Electron Microscopy (LCTEM) is a type of microscope that lets scientists see how materials behave in liquid form. LCTEM uses special tools called liquid cells, which are like tiny, transparent sandwiches that hold the study liquids steady between their layers and allow electron beams to pass through. These electron beams help create detailed images of what’s happening between the liquid cells at the atomic level.
LCTEM is especially significant for studying processes that involve rapid changes where timing and precision are crucial, such as crystallization, which occurs when atoms or molecules arrange themselves in a structured pattern. Real-time imaging inside the liquid cells while mixing two or more solutions required for crystallization has been a challenge as the process of mixing often obscures the liquid, leading to cloudy images.
In this groundbreaking study, researchers have successfully demonstrated an innovative method for observing the crystallization process of delicate molecules in real time using Liquid Cell Transmission Electron Microscopy (LCTEM). The research focused on a technique that allows the mixing of two different solvents inside a controlled microscopic environment without compromising imaging quality.
The researchers were particularly interested in observing how a molecule called R-BINOL-CN forms crystals when dissolved in liquid chloroform. When another liquid, methanol, is introduced into the chloroform solution, it acts as an antisolvent. This means it doesn’t dissolve the R-BINOL-CN, instead encouraging it to form crystals quickly.
In the experiment, researchers dissolved R-BINOL-CN in chloroform and prepared to mix it with methanol to watch the crystallization process. Using their new technique, researchers could introduce and switch between these liquids while maintaining clear images of what's happening on the LCTEM. This setup allowed them to see real-time transformations on a tiny scale. When methanol was absent, the molecules tended to form large clusters of particles. However, chain-like structures developed with methanol, which led to the formation of crystals.
The research opens doors to a better understanding of the crystallization process and better utilization of the LCTEM technology. This is particularly helpful in the pharmaceutical industry. The ability to control and visualize the crystallization process is invaluable in producing medications. Medicines often require precise crystal forms to ensure effective and stable drug delivery. With insights gained from this research and using the clear images from an LCTEM, pharmaceutical companies can better manipulate molecular structures to create optimized drugs with consistent quality.
Looking ahead, researchers are interested in refining the LCTEM technique to make it more widely applicable and accessible. This includes developing liquid cells with enhanced control over the mixing process that might integrate automated systems or involve more sophisticated on-chip flow channels. These advancements could enable scientists to conduct even more precise experiments and expand the range of materials studied.
This research news was partly generated using artificial intelligence and edited by an editor at Research Matters