A new technique allows for an in-depth, high-resolution examination of human cells
The thrill of the unknown may be relied upon to keep us on our toes in movie theaters, living rooms, and even laboratories. However, scientists no longer have to speculate about the cells’ secret chemical landscape.
Researchers at the Beckman Institute for Advanced Science and Technology were motivated by this same excitement to create a novel technique that allows one to “see” the fine details and chemical make-up of a human cell with unparalleled clarity and precision. Their method, which was published in PNAS earlier this week, approaches signal identification in a unique and counterintuitive way.
The study’s principal investigator, Rohit Bhargava, a professor of bioengineering at the University of Illinois Urbana-Champaign, called biology one of the most intriguing disciplines of their time because there has always been a gap between what we can see and what we cannot.
Since they are the smallest functioning units in our bodies, cells have long captured the curiosity of scientists who want to know what they are comprised of and where each component is located. An all-encompassing cellular blueprint that can be utilized to research biology, chemistry, materials, and more is created when the “what” and the “where” are combined.
Prior to this investigation, getting a high-resolution copy of the blueprint was practically unheard of.
Now more than ever, the researchers can look within cells in a lot finer resolution and with tremendous chemical detail. This finding raises a variety of possibilities, including a fresh approach to look at the combination chemical and physical factors that control human growth and disease.
The researchers’ approach expands on earlier developments in chemical imaging.
Chemical imaging makes use of invisible infrared light to reveal a sample’s internal workings, as opposed to optical microscopy, which illuminates surface-level aspects like color and structure using visible light.
A cell’s temperature increases and it expands when it is exposed to IR light. The researchers can compare a poodle to a park seat to see that no two items absorb infrared wavelengths exactly the same way. Night vision goggles also show that warmer objects generate stronger IR signatures than cooler ones. The same is true inside a cell, where several types of molecules each release a particular chemical signature and absorb IR light at a little different wavelength. Researchers can identify each one’s location by spectroscopically analyzing the absorption patterns.
The researchers do not evaluate the absorption patterns as a color spectrum, in contrast to night vision goggles. Instead, scientists use a signal detector, which is a tiny beam attached to the microscope on one end and has a microscopic tip that scrapes the surface of the cell like a record player’s nanoscale needle, to interpret the IR waves.
Over the past ten years, advances in spectroscopy have concentrated on continuously boosting the intensity of the early IR wavelengths.
The researchers said that it is an intuitive strategy because their conditioning tells them that bigger signals are better. A cell will be easier to observe the stronger the IR signal, the hotter it will become, the more it will grow, and so on.
This method hides a significant drawback. The velocity of the signal detector increases as the cell enlarges and produces “noise” in the form of so-called static that makes precise chemical measurements more difficult.
Seth Kenkel, a postdoctoral researcher in Professor Bhargava’s lab and the study’s lead author, described the situation as being similar to turning up the knob on a staticky radio station: the music grows louder, and so does the static.
In other words, no matter how strong the IR signal got, chemical imaging couldn’t become any better.
The researchers needed a way to stop the noise from growing along with the signal.
By separating the IR signal from the detector’s movement, the researchers’ solution to noisy cellular imaging enables amplification without the introduction of more noise.
The researchers experimented with the weakest IR signal they could manage to ensure they could implement their solution before increasing the strength, as opposed to concentrating their efforts on the strongest IR signal feasible. Starting small allowed the researchers to pay tribute to a decade of spectroscopic research and establish the foundation for the field’s future, though it was counterintuitive.
Researchers liken the approach to a road trip gone wrong.
Consider spectroscopic researchers traveling to the Grand Canyon in a car. Everyone would naturally assume that the faster the car drives, the quicker they will arrive at their destination. However, the issue is that the vehicle is traveling east from Urbana.
The IR signal is equivalent to the speed increase of the imaginary car.
They stopped, consulted a map, and turned the car in the appropriate way. Now, the field can be efficiently advanced thanks to the enhanced speed and signal.
A scale 100,000 size smaller than a strand of hair, the researchers’ “map” permits high-resolution chemical and structural imaging of cells at the nanoscale. This method is notable for not using fluorescent tagging or coloring molecules to make them more visible under a microscope.
Even though Beckman’s Microscopy Suite’s equipment was essential for the study’s experimental phase, the concept itself wasn’t the result of cutting-edge technology; rather, it sprang from a culture that encouraged inquiry, innovative problem-solving, and a diversity of viewpoints.
The Beckman Institute is a fantastic location because of this. Spectroscopy, mechanical engineering, signal processing, and of course biology were all relevant fields for this study. Nowhere else can these fields be combined flawlessly like Beckman can. This research is a prime illustration of how Beckman successfully combines interdisciplinary science with cutting-edge science and technology.
Seth Kenkel et al. (2022). Chemical imaging of cellular ultrastructure by null-deflection infrared spectroscopic measurements, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2210516119
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