It has been a great year for movies with Superman, the last part of The Conjuring, the Demon Slayer Infinity Castle movie, and many others. Even the finale of Wicked is out, which is super exciting. 

And so, in the spirit of movies, here is a recommendation from the science section — molecular movies: an endeavour in trying to catch the motion of molecules over time. Molecular movies are a particular research focus and tool at Dwayne Miller’s lab in the Departments of Physics and Chemistry at U of T. Alex Wainwright — a PhD candidate from the lab — spoke on the topic in an interview with The Varsity. 

Behind the scenes

According to Wainwrite, the name ‘molecular movies’ is a “bit of a misnomer.” You can’t really take a camera, record, and then watch molecules moving like actors on a screen. 

A regular video recording is a sequence of images taken quickly and stitched together as the actor moves. However, molecules move far too fast for us to be able to do that with them. By the time one picture is taken — even with one of our fastest cameras — the molecule has already moved on or been damaged. 

To combat this, researchers repeat the same chemical process over and over again, and then take ‘pictures’ of that process at different times instead. As Wainwright puts it, “instead of watching someone walk from start to finish… [for] 10 seconds of walking, we would take a photo at, let’s say, every microsecond, and every time we take the photo, the person would have to go back to the start, and we try to take photos again until we got the entire movie.” 

The actual ‘camera’ in a molecular movie — at the Miller lab — is ultra-fast electron diffraction (UED), which uses a pump-probe technique. 

According to Wainwright, “everybody’s done a pump probe, whether or not they realize it.” Think about poking someone so that they make a funny face and then taking a picture of them — you’ve just done a pump-probe. 

In molecular movies, the ‘poke’ — or probe — that causes a reaction of interest is a very short pulse of light. After the reaction starts, a beam of electrons — small negatively-charged particles that act as the ‘camera’ — hits the sample. The data collected from the electron’s diffraction pattern — the way the electron particles bend around the molecules — can be analyzed and processed into a movie. 

Why use UED? 

Regular camera pictures are constructed from a somewhat similar principle by capturing visible light bouncing off objects. However, because of their small size, molecules need very short wavelengths to be viewed — the smaller the wavelength, the higher the resolution. 

Alternatively, molecular movies can be made using X-ray diffraction, which uses very short wavelengths of light, instead of electrons. According to Wainwright, UED remains “a relatively niche way of doing things” because of the specialized, technical expertise required to run and understand the data. 

Additionally, because electrons are so small and reactive, UED needs to be conducted in a vacuum to avoid interactions with air particles. So, “there’s this other expertise and skill set you have to have of putting things under vacuum and having a sample that’s stable under vacuum.” X-rays can easily travel through the air, though, so they are much more suited to experiments that must be done under atmospheric conditions or in normal air. 

However, Wainwright emphasized that while “they each have their own advantages and disadvantages, the real advantage of electrons… is that it allows for you to get higher resolution because the wavelength of an electron is so much shorter than the wavelength of the light that you use in an X-ray diffraction.” 

And action!

We can record molecular reactions fairly well using UED, but what is the data useful for? As it turns out, the applications are numerous. 

Let’s go back a couple of decades. In 2003, Bradley J. Siwick — at the time a member of the Miller lab and now an Associate Professor at McGill — and his team released a notable paper in the acclaimed academic journal, Science. He recorded the first atomically-resolved movie, which is detailed enough that some of the smallest levels of matter interactions are viewable. The movie showed a transition reaction — the melting of aluminum — using UED. 

The paper showed that “if you can excite a solid fast enough, it will melt inside out instead of outside in,” as Wainwright explained. This process is known as homogenous nucleation. 

Notably, in the aluminum, the nucleation didn’t spread to the surrounding area and was confined to around 10 atoms per nucleation site. Interestingly, this can also be applied to water molecules, so that you can “actually boil water without heating up the material around the water.” 

Considering that we’re mostly made up of water, this has some interesting applications in medicine and biology. In fact, a major problem with many laser surgery techniques is the surrounding tissue damage that happens as a result of explosive heterogeneous nucleation — the typical melting from the outside in process once the surrounding tissue is heated by a laser. 

However, cross-applying the method from the 2003 paper, surgeons can instead use fast, short laser pulses to obtain very precise and clean tissue removal. As Wainwright explained, by cutting “a tissue with this laser beam… only the spot that was irradiated by the laser is boiled, and it is boiled so fast that information cannot be transmitted away,” meaning there is no surrounding damage. 

According to Wainwright, “this is looking to be one of the first techniques towards scarless surgery.” The Picosecond InfraRed Laser (PIRL) scalpel was created by researchers to use these insights, but it is still in the process of being widely adopted and advanced further. 

According to Wainwright, “[the Miller group] is now exploring how to use these lasers to remove material very selectively.” They are also collaborating with Light Matter Interaction — a company developing and commercially selling these lasers. So, even though the research for this technology has existed for 20 years, the medical device development and distribution are still underway today.

Of course, having the ability to visualize molecules to the degree that UED affords has numerous applications in understanding how various processes work. For example, Wainwright highlighted that recent and ongoing research in the lab covers a wide variety of topics — visualizing a biomolecular reaction is a recent example. Biomolecules refer to molecules found in living organisms; some big examples include DNA and proteins.

Molecular movies created using UED promise to be a useful tool in understanding the motion of molecules and how various reactions proceed to a great level of resolution. Like how understanding the phase transition in aluminum led to a new level of surgical precision, a greater level of understanding of molecular processes is key to further innovations. While this marks a wrap on this article, it’s far from a wrap for UED, a molecular visualization field that is constantly growing and has an exciting place in future research.