Researchers at the Beckman Institute for Advanced Science and Technology have developed a new way to “see” the fine structure and chemical composition of the human cell with unparalleled clarity and resolution.
That’s why Jaws swam out of sight for more than an hour and hints at the magic of gift wrapping. In movie theaters, living rooms, and even laboratories, the thrill of the unseen can be counted on to keep us guessing. But when it comes to the hidden chemical world of cells, scientists no longer need to wonder.
Inspired by this same thrill, researchers at the Beckman Institute for Advanced Science and Technology have developed an innovative method to “see” the fine structure and chemical composition of the human cell with unparalleled clarity and precision. Their style appeared in PNAS Earlier this week, he took a creative — and counterintuitive — approach to detecting cues.
said Rohit Bhargava, a professor of bioengineering at the University of Illinois, Urbana-Champaign who led the study.
As the smallest functional units in our bodies, cells have long intrigued researchers interested in identifying what they are made of and where each component resides. Together, the “what” and “where” make up an all-purpose cell chart that can be used to study biology, chemistry, materials, and more.
Prior to this study, obtaining a high-resolution copy of that chart was among the impossible.
“Now, we can see inside cells with much finer resolution and in important chemical details more easily than ever before,” Bhargava said. “This work opens up a host of possibilities, including a new way to examine the combined chemical and physical aspects that govern human development and disease.”
The researchers’ work builds on earlier steps in the field of chemoimaging.
While light microscopy uses visible light to illuminate surface-level features such as color and structure, chemical imaging uses invisible infrared light to reveal the inner workings of a sample.
When a cell is exposed to infrared light, it heats up and expands. We know from night vision goggles that no two objects absorb infrared wavelengths in exactly the same way; Comparing a poodle to a park bench is proof enough that warmer objects emit stronger infrared signals than cooler ones. The same is true inside a cell, where each type of molecule absorbs infrared light of a subtly different wavelength and emits a unique chemical signature. Examining the absorption patterns — a method called spectroscopy — allows researchers to pinpoint where each is.
Unlike night vision goggles, the researchers do not analyze absorption patterns as a color spectrum. Instead, they interpret the infrared waves with a signal detector: a microbeam fixed to the microscope at one end, with the tiny tip scratching the surface of the cell like the nano-needle of a record player.
Innovations in spectroscopy over the past decade have focused on steadily increasing the power of the initial infrared wavelengths.
“It’s an intuitive approach because we’re conditioned to think of bigger signals as better. We think, ‘The stronger the infrared signal, the hotter the cell, the more it expands, and the easier it is to see,'” Bhargava said.
This approach conceals a major setback. As the cell expands, the motion of the signal detector becomes exaggerated and generates ‘noise’: a so-called constant that impedes accurate chemical measurements.
“It’s like turning on the dial on a static radio station – the music gets louder, and so does the static,” said Seth Kinkel, a postdoctoral researcher in Professor Bhargava’s lab and lead author of the study.
In other words, no matter how strong the infrared signal is, the quality of chemoimaging cannot age.
“We needed a solution to stop the noise from increasing along with the signal,” Kinkel said.
The researchers’ treatment of noisy cell imaging works by separating the infrared signal from detector motion, allowing for amplification without additional noise.
Instead of focusing their energies on the strongest possible infrared signal, the researchers started by experimenting with the smallest signal they could manage, to ensure they could implement their solution effectively before increasing the strength. Although “counter-intuitive,” according to Kinkel, starting small allowed the researchers to honor a decade of research in spectroscopy and laid a critical foundation for the field’s future.
Bhargava is like approaching a road trip derailed.
“Imagine that the spectroscopy researchers were in a car heading to the Grand Canyon. Of course, everyone thinks that the faster the car is moving, the faster they will get to the destination. But the problem is, the car is going east from Urbana,” he said.
Increasing the speed of the virtual car is the same as boosting the infrared signal.
“We stopped, looked at the map, and pointed the car in the right direction. Now, the increased speed—the increased signal—can effectively move the field forward.”
The researchers’ ‘map’ enables high-resolution chemical and ultrastructural imaging of cells at the nanoscale – a scale 100,000 times smaller than a strand of hair. It is worth noting that this technique is free of fluorescent markers or dye particles to increase its clarity under the microscope.
While the facilities in Beckman’s Microscopy Suite were crucial to the pilot phase of the study, the idea itself arose not from cutting-edge technology, but from a culture that supports curiosity, unconventional problem-solving, and diverse perspectives.
“This is why the Beckman Institute is such an amazing place,” Bhargava said. “This project needed ideas from spectroscopy, from mechanical engineering, from signal processing, and of course biology. You couldn’t bring these fields together so seamlessly anywhere else than at Beckmann. This study is a classic example of Beckmann’s blend of interdisciplinary science at the cutting edge of science and technology.” advanced.”
The research reported in this news release was supported in part by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award numbers T32EB019944 and R01EB009745, as well as by the National Science Foundation under award number 2153032. This content is the sole responsibility of the authors and does not necessarily represent endorsements. Official view of the National Institutes of Health.