Dynamic partial-wave spectroscopic (PWS) microscopy allows researchers to observe intracellular structures as small as 20 nanometers – smaller than those visible by optical microscopes – in three dimensions at a millisecond resolution, all without using disruptive labels or dyes. Development of this technique is made possible by supercomputers.
At the McCormick School of Engineering at Northwestern University, Allen Taflove (a professor of electrical and computer engineering) and his research team are furthering dynamic PWS using simulations run on the Mira supercomputer. Mira, which is housed at the Argonne Leadership Computing Facility (ALCF), is an 8.6 Linpack petaflop IBM system with BlueGene/Q Power 16C 1.6GHz processors. Deployed in 2012, Mira still stands as the 24th fastest publicly-ranked supercomputer as of the June Top500 list. Recently, Taflone and his team were awarded an additional five million node-hours on Mira thanks to the Department of Energy’s INCITE program.
The researchers first used Mira to validate dynamic PWS by evaluating uniform-size nanospheres in simulation, allowing them to test what the dynamic PWS “saw” against physics-based analytical theories. “The analytical theory was initially not quite in accord with the experimental data obtained from the nanosphere phantoms, whereas the Angora simulations on Mira were much closer and showed the correct trend,” Taflove said. “The Angora simulations performed on Mira for the nanosphere phantoms ultimately did get the analytical theory rounded into shape.”
Then, they set about a more ambitious task: putting the tool to work in a real-world use case. They bombarded cancer cells with ultraviolet (UV) radiation, tracking the cells with dynamic PWS throughout the process. They found that when the UV light was applied to the cells for 10 to 20 minutes, the macromolecules in the cancer cells (which are responsible, for instance, for assembling new proteins or repairing DNA) briefly spasmed… and then died. This phenomenon – which the researchers are calling a “cellular paroxysm” – represents an “as-yet-to-be-found” form of cell death, and it may have implications for future cancer treatments.
“Using the ALCF Mira resource, we validated the dynamic PWS microscopy technique and successfully applied it to study the time-domain response of cancer cells subjected to a lethal stimulus,” Taflove says. “Millisecond-resolution dynamic PWS is a proven tool for tracking macromolecular motion within living cells. Now, let’s apply it to investigate novel potential cancer therapies.”
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