World's most powerful NMR spectrometer delivered to Scripps Research Institute

The most powerful, high-resolution nuclear magnet resonance (NMR) spectrometer ever constructed has just been delivered to The Scripps Research Institute. According to Peter Wright, Chairman, Department of Molecular Biology, the new NMR, referred to by the frequency at which it operates, 900 mega-hertz (MHz), will become the centrepiece of one of the world's largest and most capable collections of NMR instruments. The Scripps Research Institute (TSRI) has more than 13 instruments at or above 500 MHz. Wright's enthusiasm is obvious as he comments, "It's fantastic. The capabilities of this instrument take us to a new level. It's a very big deal to have the first major instrument of this type. It reinforces our position at the leading edge of molecular and structural biology."NMR spectroscopy is a diagnostic tool aiding in the determination of chemical structures of both simple and highly complex molecules. Development of NMR began in the 1940s and gained momentum in the 1950s with commercial instruments of 60 MHz becoming available in the late 1950s/early 1960s. NMR was first used by organic chemists to determine chemical structures of relatively simple molecules. A series of advances including development of more powerful electromagnets, Fourier transform techniques, and 2-dimensional and 3-dimensional NMR analysis enabled the structures of ever more complex and higher molecular weight molecules to be determined. NMR is also the basis for magnetic resonance imaging, a similar technique of increasing use in medical diagnostics. In a biomedical research context, NMR provides the co-ordinates of the atoms comprising biologically important molecules in solution. This information enables scientists to determine the structure-function relationships of molecules that lie at the heart of understanding fundamental biological processes.The 900 MHz instrument will provide TSRI principal investigators Peter Wright, Jane Dyson, Jamie Williamson, Jefferey Kelly and their research groups with the ability to determine the structures of high molecular weight proteins and nucleic acids in dilute solution with greater sensitivity and resolution and in a more efficient and productive way according to John Chung, Director of Biomolecular NMR Facilities at TSRI. In all, up to about 50 postdoctoral research associates and graduate students may be involved in research using the new instrument. Of primary interest are protein and nucleic acid structures but macromolecular assemblies between proteins, nucleic acids and lipids will also be studied. Biological phenomena such as protein folding and cell cycle regulation pathways will be studied using the 900 MHz instrument, as will other areas in the rapidly expanding field of structural proteomics.Determining the three-dimensional structures of proteins and nucleic acids provides important insights into basic questions about how living organisms function and change, and how particular alterations can lead to human disease. Structural biology is particularly important in today's research environment. Chung notes, "While terabytes of genomic data are now available, the structures of most of the proteins the genes are coding for and their functions remain unknown." The 900 MHz instrument will play a major role in determining the structure of these proteins and helping decode the mystery of which genes encode specific protein functionality.The 900 MHz instrument is the first of its kind and has been several years in the making by its German manufacturer, Bruker Instruments, Inc. According to John Chung, Bruker is now working to deliver approximately a dozen 900 MHz instruments for other institutions. He estimates the instrument price at "several millions" (dollars). The 900 MHz magnet is based on Bruker's proprietary sub-cooled technology for ultra-high field NMR. The magnet is the heart of any NMR instrument and this one consists of several superconducting coils surrounded by an outer Dewar flask containing liquid helium. Advanced superconducting wires make possible the increased current, forces and stored energy in the novel magnet. These wires and advanced jointing technology minimise magnetic field drift rates thus improving instrument resolution. According to Chung, "For high resolution the field produced by the magnet must be homogeneous to one part in a billion over a few cubic centimetres."In a NMR experiment, a sample in a long tube is inserted into this space. Atomic nuclei of molecules inside the tube give detectable responses to a radio frequency signal emitted by the inner magnet coil at varying frequencies. These nuclei typically have an odd mass number such as 1H and 13C. The magnetic moment of these nuclei may be oriented parallel or anti-parallel to the moment of the magnetic field applied by the NMR magnet. The frequency of applied electromagnetic radiation necessary to induce a transition from one of these nuclear spin states to the other is termed the resonance frequency. The resonance frequency of each atom provides information on the chemical environment in which that atom resides. Different chemical environments give rise to characteristic resonance frequencies.A typical experiment involves scanning a range of frequencies and recording the resonance frequencies of the atoms in the sample. A NMR spectrum is unique for a particular molecule and the structure of a molecule can be determined from its spectrum. The more complex the molecule, the more absorption frequency peaks are observed in its spectrum and the more difficult the chemical structure is to determine.Will there be even more powerful NMR instruments in the future? Chung foresees the continuing development of the 900 MHz machine and in the future even more powerful instruments capable of expanding the fields of structural biology and structural proteomics further. He expects that higher magnetic field strength instruments of over 1 giga-hertz (GHz) will be developed. However, he notes that current technology has carried field strength about as high as it can and technological breakthroughs will be needed to carry the field strength to over 1 GHz. He sees improvements in superconducting materials and perhaps use of high temperature superconductors plus improved superconducting junctions as being needed. Chung estimates improved instruments of about 1 GHz and higher are a minimum of five years away.But, even development of a 1GHz instrument will not render smaller magnet instruments obsolete. Currently 500, 750 and 800 MHz instruments are studying and helping solve important biomedical problems and will continue to do so even as the 900 MHz NMR becomes the instrument of choice for many problems.

World's most powerful NMR spectrometer delivered to Scripps Research Institute

The world's most powerful, high-resolution nuclear magnet resonance spectrometer provides researchers with the ability to determine structures of high molecular weight proteins and nucleic acids with much greater sensitivity and resolution.

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