The World's Most Powerful NMR Magnet Arrives at TSRI

By Jason Socrates Bardi

The largest nuclear magnetic resonance (NMR) magnet ever constructed arrived last week at The Scripps Research Institute (TSRI), where it was assembled into the most sensitive NMR instrument on the planet.

The new NMR, referred to by its maximum radio frequency, 900 MHz, is now the centerpiece of TSRI's premier collection of NMR instruments.

"It's fantastic," says Peter Wright, professor and chair of the Department of Molecular Biology. "The capabilities of this instrument take us to a new level."

Now in its permanent home in one corner of the Buddy Taub Center for Molecular Structure and Design, the 900 MHz instrument sits next to the 800 MHz instrument that has been in the same building since 1998. Although appearing only a little taller and a little fatter than the 800, the 900 represents a major breakthrough in technology.

"It's rather a technological triumph," says Associate Professor Jane Dyson of the new machine.

The instrument, which is the first of its kind and has been several years in the making by its German manufacturer, Bruker Instruments, Inc., is currently being cooled down to its operating temperature of 2 degrees Kelvin above absolute zero with 5000 liters of nitrogen and up to 4,500 liters of liquid helium. The instrument's magnet is actually several miles of ultra-high technology Niobium-Tin and Niobium-Titanium superconducting coils sitting directly in the helium bath, which is surrounded by a vacuum dewar and a liquid nitrogen bath.

 



This magnet will be charged with over two hundred amperes of persistent super-conducting current. Through induction, this current will produce a stable magnetic field of 21 tesla, which is very large compared to a hospital MRI 2 tesla magnet. In addition, the field is remarkably homogenous: better than one part per billion over a couple of cubic centimeters volume.

Once filled and charged, the instrument will be calibrated, tested for a few weeks, then put to use by research groups at TSRI.

Improvements to Resolution and Sensitivity

"There are already problems waiting to go into it," says Wright. "Instantly—as soon as it's available."

Some of those problems will take advantage of the improvements of the 900 over existing lower field instruments at TSRI. For instance, the 900 is expected to be 40 to 50 percent more sensitive (peak heights) and have greater resolving power (peak separations) than the 800 MHz instrument.

The increased resolution will help separate peaks of two close chemical shifts that would normally overlap. "The first thing we do will probably be to exploit this resolution to study systems that were not possible before," says Dyson.

The increased sensitivity should allow measurements to be taken on samples with lower protein concentrations. Typically, some proteins, big and small, don't behave well at high concentrations. Modern experiments require the protein to be stable around 100 ÁM to1mM, for instance, but this is impossible for some systems because the molecules may dimerize, aggregate, or precipitate at that concentration.

The concentration can be reduced but only at the cost of reducing the signal-to-noise ratio, with the risk of losing the signal altogether. But the increased sensitivity of the 900 should allow concentrations to be lowered even further before the signal disappears.

However, even with the increased resolution and sensitivity, many interesting systems remain elusive to NMR because they are either too big, too insoluble, or too complicated. The size limitations for structures that may be obtained through conventional NMR, for instance, is around 30 to 40 kD, but many proteins are simply much larger than this.

Membrane proteins are also complicated to deal with. These proteins, which make up about one third of all the genes in the human genome, are notoriously hard to crystallize and would make excellent problems for NMR spectroscopists if they weren't so large and insoluble.

Then there are partially folded and unfolded systems that are too complicated to study with conventional NMR because the increased flexibility of the unfolded polypeptides significantly increases the difficulty of analyzing the spectra. Much can be gained by studying the partly folded states of proteins and observing how they fold. Do they make secondary or tertiary structures? How flexible are their backbones and how flexible are their side chains?

"All these things we can get at," she says, "but because the spectra are so overlapped, we need this big machine."

"Until now we haven't had the tools to study these things—the unfolded proteins, the membrane proteins, the huge proteins—you can't look at them because they are so difficult," says Dyson.

 

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"There are already problems waiting to go into [the 900 MHz]," says Peter Wright, professor and chair of the Department of Molecular Biology.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


"It's rather a technological triumph," says Associate Professor Jane Dyson.