Monday, July 13, 2026
New probe could help trace Alzheimer's-linked lipids one cell at a time - Chemistry - Biochemistry - Analytical Chemistry
Cells
sitting side by side in the same tissues are not identical. Each cell carries
its own subtly different chemical signature—a hidden individuality that can
reveal how diseases take root and spread. Now, researchers from the University
of Osaka have developed a technique sensitive enough to capture this
cell-by-cell diversity within tissues with unprecedented precision and
stability. Their study is published in the journal Analytical
Chemistry.
Changes in the chemical makeup of cells
can indicate the onset and progression of disorders such as neurodegenerative
diseases, making it important to examine such changes in detail while focusing
on the smallest possible areas. In the past, ambient sampling and ionization
methods using electrospray ionization (ESI) for mass spectrometry imaging (MSI)
have been developed.
ESI-based MSI uses a small probe to
deliver solvent (a liquid that dissolves and releases chemical components) to a
cell, detaching molecules that become charged and are then separated and
counted in a mass spectrometer. Because mammalian cells can be as small as 10
micrometers, this imaging technique must be able to produce pixel sizes smaller
than that.
"One issue with mass spectrometry
imaging is that, as we focus on smaller and smaller regions within the cell, we
require increasingly high sensitivity and stability," says lead author
Takao Yasuda.
To
address this issue, the researchers looked at ways to improve the performance
of an ESI-based MSI system named tapping-mode scanning probe ESI (t-SPESI),
which was originally invented by corresponding author Yoichi Otsuka. In the
t-SPESI process, an extremely fine fused silica probe "taps" the cell
repeatedly, alternately delivering a solvent and extracting components for
analysis. This tapping motion enables the use of an extremely small amount of
solvent to examine smaller areas but requires high sensitivity and good
stability.
"Two factors currently limit the
performance of this technique," senior author Otsuka says. "These are
the long pathway between the probe and the mass spectrometer, and the tendency
for cell components to adhere to the probe surface over time."
On this basis, the research team
achieved higher sensitivity by miniaturizing the complex analytical apparatus,
reducing device mass by 45% and ion pathway length by 56%. Shortening the tube
more than doubled the signal intensity. To ensure long-term stability by
reducing the adhesion of sample to the probe, the silica probe surface was
coated with a fluorine-containing chemical, similar to a nonstick coating on a
kitchen implement.
As
a test of this new system, mouse brain tissue samples were analyzed, and the
team successfully visualized lipid distributions, including lipid classes
previously implicated in Alzheimer's and Parkinson's disease, with a pixel size
of 5 micrometers, corresponding to fine tissue structures, and with good
stability.
The team expects that examining cells within tissues using this technology will provide new insights for disease research and treatment. With further optimization, such as of probe size, even better performance could be achieved, helping future studies uncover the mechanisms behind many disorders and advancing understanding of them.
Provided by University of Osaka
Source: New probe could help trace Alzheimer's-linked lipids one cell at a time
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