Nav: Home

Novel electron microscopy offers nanoscale, damage-free isotope tracking in amino acids

January 31, 2019

OAK RIDGE, Tenn., Jan. 31, 2019--A new electron microscopy technique that detects the subtle changes in the weight of proteins at the nanoscale--while keeping the sample intact--could open a new pathway for deeper, more comprehensive studies of the basic building blocks of life.

Scientists at the Department of Energy's Oak Ridge National Laboratory described in the journal Science the first use of an electron microscope to directly identify isotopes in amino acids at the nanoscale without damaging the samples.

Isotopes are commonly used to label molecules and proteins. By measuring the variations in the vibrational signatures of the molecule, the electron microscope can track isotopes with unprecedented spectral precision and spatial resolution.

The technique does not destroy the amino acids, allowing for real-space observation of dynamic chemistry and creating a foundation for a host of scientific discoveries from simple to complex biological structures across the life sciences.

"The way we understand the progression of diseases, human metabolism and other complicated biological phenomena is based on interactions between proteins," said Jordan Hachtel, ORNL postdoctoral fellow and lead author. "We study these interactions by labeling specific proteins with an isotope and then tracking it through a chemical reaction to see where it went and what it did."

"Now, we can track isotopic labels directly with the electron microscope, meaning we can do it with a spatial resolution comparable to the actual size of the proteins," Hachtel added.

Their novel experiment, which took place at ORNL's Center for Nanophase Materials Sciences, used monochromated electron energy-loss spectroscopy, or EELS, in a scanning transmission electron microscope, or STEM. The technique the scientists used is sensitive enough to distinguish between molecules that differ by a single neutron on a single atom. EELS was used to capture the minute vibrations in the molecular structure of an amino acid.

"Isotopic labels are typically seen on the macroscopic level using mass spectrometry, a scientific tool that reveals a sample's atomic weight and isotopic composition," said Juan Carlos Idrobo, ORNL staff scientist and corresponding author. "Mass spectrometry has incredible mass resolution, but it typically doesn't have nanometer spatial resolution. It's a destructive technique."

A mass spectrometer uses an electron beam to break a molecule apart into charged fragments that are then characterized by their mass-to-charge ratio. Observing the sample at the macroscale, scientists can only infer statistically what chemical bonds were likely to have existed in the sample. The sample gets destroyed during the experiment, leaving valuable information undiscovered.

The new electron microscopy technique, as applied by the ORNL team, offers a gentler approach. By positioning the electron beam extremely close to the sample, but without directly touching it, the electrons can excite and detect the vibrations without destroying the sample, allowing observations of biological samples at room temperature over longer periods of time.

Their result constitutes a breakthrough for electron microscopy, since the negatively charged electron beam is typically sensitive only to the protons, and not the neutrons. "However, the frequency of the molecular vibrations is dependent on the atomic weight, and the accurate measurement of these vibrational frequencies opens the first direct channel to measure isotopes in the electron microscope," said Idrobo.

The ORNL-led research team expects their potentially game-changing technology would not replace but rather complement mass spectrometry and other conventional optical and neutron-based techniques currently used to detect isotopic labels.

"Our technique is the perfect complement to a macroscale mass spectrometry experiment," Hachtel said. "With the pre-knowledge of the mass spectrometry, we can go in and spatially resolve where the isotopic labels are ending up in a real-space sample."

Beyond the life sciences the technique could be applied to other soft matter such as polymers, and potentially in quantum materials where isotopic substitution can play a key role in controlling superconductivity.
Co-authors of the study titled, "Identification of Site-Specific Isotopic Labels by Vibrational Spectroscopy in the Electron Microscope," included Jordan A. Hachtel, Jingsong Huang, Ilja Popovs, Santa Jansone-Popova, Jong K. Keum, Jacek Jakowski and Juan Carlos Idrobo all of ORNL, and Tracy C. Lovejoy, Niklas Dellby and Ondrej L. Krivanek of Nion Co., the designers and manufacturers of the electron microscope and spectrometer used in the experiments.

The research was supported by DOE's Office of Science and used a monochromated, aberration-corrected scanning transmission electron microscope, or MAC-STEM, and other resources at ORNL's Center for Nanophase Materials Sciences, a DOE User Facility.

UT-Battelle manages ORNL for DOE's Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit

DOE/Oak Ridge National Laboratory

Related Amino Acids Articles:

Alzheimer's: Can an amino acid help to restore memories?
Scientists at the Laboratoire des Maladies Neurodégénératives (CNRS/CEA/Université Paris-Saclay) and the Neurocentre Magendie (INSERM/Université de Bordeaux) have just shown that a metabolic pathway plays a determining role in Alzheimer's disease's memory problems.
New study indicates amino acid may be useful in treating ALS
A naturally occurring amino acid is gaining attention as a possible treatment for ALS following a new study published in the Journal of Neuropathology & Experimental Neurology.
Breaking up amino acids with radiation
A new experimental and theoretical study published in EPJ D has shown how the ions formed when electrons collide with one amino acid, glutamine, differ according to the energy of the colliding electrons.
To make amino acids, just add electricity
By finding the right combination of abundantly available starting materials and catalyst, Kyushu University researchers were able to synthesize amino acids with high efficiency through a reaction driven by electricity.
Nanopores can identify the amino acids in proteins, the first step to sequencing
While DNA sequencing is a useful tool for determining what's going on in a cell or a person's body, it only tells part of the story.
Differentiating amino acids
Researchers develop the foundation for direct sequencing of individual proteins.
Simulating amino acid starvation may improve dengue vaccines
In a new paper in Science Signaling, researchers at the University of Hyderabad in India and the Cornell University College of Veterinary Medicine show that a plant-based compound called halofuginone improves the immune response to a potential vaccine against dengue virus.
CoP-electrocatalytic reduction of nitroarenes: a controllable way to azoxy-, azo- and amino-aromatic
The development of a green, efficient and highly controllable manner to azoxy-, azo- and amino-aromatics from nitro-reduction is extremely desirable both from academic and industrial points of view.
Origin of life insight: peptides can form without amino acids
Peptides, one of the fundamental building blocks of life, can be formed from the primitive precursors of amino acids under conditions similar to those expected on the primordial Earth, finds a new UCL study published in Nature.
Researchers develop fast, efficient way to build amino acid chains
Researchers report that they have developed a faster, easier and cheaper method for making new amino acid chains -- the polypeptide building blocks that are used in drug development and industry -- than was previously available.
More Amino Acids News and Amino Acids Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at