From MIT Tech Review: “This Microscope Reveals Human Biochemistry at Previously Unimaginable Scales”

MIT Technology Review
M.I.T Technology Review

February 23, 2017

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Magnetic resonance imaging is one of the miracles of modern science. It produces noninvasive 3-D images of the body using harmless magnetic fields and radio waves. And with a few additional tricks, it can also reveal details of the biochemical makeup of tissue.

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That biochemical trick is called magnetic resonance spectroscopy, and it is a powerful tool for physicians and researchers studying the biochemistry of the body, including metabolic changes in tumors in the brain and in muscles.

But this technique is not perfect. The resolution of magnetic resonance spectroscopy is limited to length scales of about 10 micrometers. And there is a world of chemical and biological activity at smaller scales that scientists simply cannot access in this way.

So physicians and researchers would dearly love to have a magnetic resonance microscope that can study body tissue and the biochemical reactions within it at much smaller scales.

Today, David Simpson and pals at the University of Melbourne in Australia say they have built a magnetic resonance microscope with a resolution of just 300 nanometers that can study biochemical reactions on previously unimaginable scales. Their key breakthrough is an exotic diamond sensor that creates magnetic resonance images in a similar way to a light sensitive CCD chip in a camera.

Magnetic resonance imaging works by placing a sample in a magnetic field so powerful that the atomic nuclei all become aligned; in other words, they all spin the same way. When these nuclei are zapped with radio waves, the nuclei become excited and then emit radio waves as they relax. By studying the pattern of re-emitted radio waves, it is possible to work out where they have come from and so build up a picture of the sample.

The signals also reveal how the atoms are bonded to each other and the biochemical processes at work. But the resolution of this technique is limited by how closely the radio receiver can get to the sample.

Enter Simpson and co, who have built an entirely new kind of magnetic resonance sensor out of diamond film. The secret sauce in this sensor is an array of nitrogen atoms that have been embedded in a diamond film at a depth of about seven nanometers and about 10 nanometers apart.

Nitrogen atoms are useful because when embedded in diamond, they can be made to fluoresce. And when in a magnetic field, the color they produce is highly sensitive to the spin of atoms and electrons nearby or, in other words, to the local biochemical environment.

So in the new machine, Simpson and co place their sample on top of the diamond sensor, in a powerful magnetic field and zap it with radio waves. Any changes in the state of nearby nuclei causes the nitrogen array to fluoresce in various colors. And the array of nitrogen atoms produces a kind of image, just like a light sensitive CCD chip. All Simpson and co do is monitor this fireworks display to see what’s going on.

To put the new technique through its paces, Simpson and co study the behavior of hexaaqua copper(2+) complexes in aqueous solution. Hexaaqua copper is present in many enzymes which use it to incorporate copper in metalloproteins. However, the distribution of copper during this process, and the role it plays in cell signaling, is poorly understood because it is impossible to visualize in vivo.

Simpson and co show how this can now be done using their new technique, which they call quantum magnetic resonance microscopy. They show how their new sensor can reveal the spatial distribution of copper 2+ ions in volumes of just a few attoLitres and at high resolution. “We demonstrate imaging resolution at the diffraction limit (~300 nm) with spin sensitivities in the zeptomol (10‐21) range,” say Simpson and co. They also show how the technique reveals the redox reactions that the ions undergo. And they do all this at room temperature.

That’s impressive work that has important implications for the future study of biochemistry. “The work demonstrates that quantum sensing systems can accommodate the fluctuating Brownian environment encountered in ‘real’ chemical systems and the inherent fluctuations in the spin environment of ions undergoing ligand rearrangement,” says Simpson and co.

That makes it a powerful new tool that could change the way we understand biological processes. Simpson and co are optimistic about its potential. “Quantum magnetic resonance microscopy is ideal for probing fundamental nanoscale biochemistry such as binding events on cell membranes and the intra‐cellular transition metal concentration in the periplasm of prokaryotic cells.”

Ref: arxiv.org/abs/1702.04418: Quantum Magnetic Resonance Microscopy

See the full article here .

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