A simple but extraordinarily difficult question has challenged scientists for decades: how can free radicals be observed directly inside living cells without damaging the cells themselves? drg. Aryan Morita, M.Sc., Ph.D., a researcher from the Department of Dental Biomedical Sciences at Universitas Gadjah Mada who is also affiliated with a research team at University Medical Center Groningen in the Netherlands, together with his collaborators, has helped answer that question. In 2022, the team published a breakthrough in the prestigious journal Nano Today: using nanoscale diamond particles as quantum sensors to detect free radicals inside living yeast cells in real time, with previously unattainable resolution.
What Are Free Radicals, and Why Are They So Difficult to Measure?
Free radicals are highly reactive, short-lived molecules. The body continuously produces them as part of normal metabolism, but when their levels become excessive, they can damage DNA, proteins, and cell membranes. This process underlies many serious diseases, ranging from cancer and heart disease to aging itself.
The problem is that free radicals occur at extremely low concentrations, typically in the nanomolar-to-micromolar range, and can disappear within nanoseconds. Existing techniques have serious limitations. Organic fluorescent dyes commonly used to detect free radicals in laboratories can undergo photobleaching, lack specificity, and may even become toxic at high concentrations. Conventional MRI, meanwhile, requires enormous numbers of atoms to generate a detectable signal and therefore cannot observe individual cells.
As a result, studying free radicals at the single-cell level has been like searching for something in complete darkness.
Diamonds That Can Sense Magnetic Signals
The team, led by Romana Schirhagl and Mayeul Chipaux, used an entirely different approach: diamond magnetometry. Nanoscale diamond particles measuring 70 nanometers—far smaller than a cell—were introduced into yeast cells (Saccharomyces cerevisiae). Inside the diamond particles are crystal defects known as nitrogen vacancy (NV) centers.
The technique relies on quantum principles. NV centers are highly sensitive to the magnetic “noise” in their surroundings. Because free radicals contain unpaired electrons, they generate weak but detectable magnetic signals. When the nanodiamond is illuminated with a laser, the time required for the NV center to return to its ground state—known as the T1 relaxation time—changes depending on the amount of free radicals in its vicinity. The shorter the T1, the higher the concentration of free radicals.
The T1 signal is analogous to the T1 signal used in conventional MRI, but here it originates from a volume at the nanometer scale inside a single cell.
“This technique gives us the ability to follow free-radical production in real time in living cells, something that was previously impossible.” — drg. Aryan Morita, M.Sc., Ph.D., lead researcher, as reported in the Nano Today publication (2023)
From Young Cells to Old Cells: What Did the Researchers Find?
The team tested four different yeast strains: a wild-type strain and three mutants, sod1Δ, tor1Δ, and pex19Δ. The sod1Δ strain lacks the superoxide dismutase (SOD1) enzyme responsible for neutralizing free radicals. As predicted, these cells had the highest free-radical burden.
The findings for tor1Δ and pex19Δ were even more interesting. Both mutants are known to have longer lifespans than normal, but the mechanism behind this phenomenon has remained unclear. Using diamond magnetometry, the researchers found that these two mutants actually had lower free-radical burdens, even in aged cells. This provides a possible explanation for their longevity: their longer lifespans may be directly related to their ability to maintain lower free-radical levels.
The study also demonstrated that antioxidants work at the cellular level. Adding L-ascorbic acid (vitamin C) increased the T1 value, indicating a reduction in free-radical levels. Glutathione (GSH), meanwhile, was effective only in the wild-type strain and not in the mutant lacking SOD1.
Another notable advantage is that the diamonds do not undergo photobleaching, are non-toxic, and the same sensor can be used repeatedly in the same cell for hours or even days. This is not possible with conventional organic dyes.
A Bridge from Yeast to Humans
Yeast was chosen for a reason. Many aging mechanisms in yeast appear to be universal, meaning that they resemble processes occurring in human cells. Chronological aging in yeast, in which cells stop dividing and essentially “wait” while continuing to age, is a relevant model for various types of non-dividing human cells, such as neurons.
The researchers state that, in principle, the same method could be applied to mammalian cells. The current limitation is the need for optical access, meaning that samples must be sufficiently transparent. In the future, however, this technique could provide new ways to test drug effects, study disease mechanisms, and even evaluate genetic mutations associated with aging.
This finding is more than an achievement in bringing quantum physics into biology. It represents a new window into one of the most fundamental processes of life: how cells age, how they survive stress, and why some live longer than others. The answer, it turns out, is stored in magnetic fluctuations that can be detected by a diamond particle measuring only a fraction of the width of a human hair.
Authors: Achmad Zam Zam Aghasy, DDS, M.Kes.; Hazra Alifia Muharam
Photo: Freepik
Source DOI: https://doi.org/10.1016/j.nantod.2022.101704