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  • richardmitnick 5:14 pm on July 5, 2017 Permalink | Reply
    Tags: , Many diseases have their origins in defective proteins, , Max Planck Institute for Solid State Research in Stuttgart, , NMR/MRI technology improvements   

    From Max Planck Institute Gesellschaft: “Nuclear magnetic resonance scanner for individual proteins” 

    Max Planck Gesellschaft

    July 05, 2017
    Prof. Dr. Jörg Wrachtrup
    Fellow at the Max Planck Institute for Solid State Research
    Universität Stuttgart
    +49 711 685-65278

    Thanks to improved resolution, a quantum sensor can now identify individual atoms in biomolecules.

    Nuclear magnetic resonance scanners, as are familiar from hospitals, are now extremely sensitive. A quantum sensor developed by a team headed by Professor Jörg Wrachtrup at the University of Stuttgart and researchers at the Max Planck Institute for Solid State Research in Stuttgart, now makes it possible to use nuclear magnetic resonance scanning to even investigate the structure of individual proteins atom by atom. In the future, the method could help to diagnose diseases at an early stage by detecting the first defective proteins.

    Green laser light transmitted via an optical fibre excites nitrogen atoms in a diamond, causing it to fluoresce with a red light. The brightness of a nitrogen atom at the edge of the diamond lattice allows conclusions to be drawn about the magnetic signals from a sample on the surface of the sensor. © University of Stuttgart.

    Many diseases have their origins in defective proteins. As proteins are important biochemical motors, defects can lead to disturbances in metabolism. Defective prions, which cause brain damage in BSE and Creutzfeldt- Jakob disease, are one example. Pathologically changed prions have defects in their complex molecular structure. The problem: individual defective proteins can likewise induce defects in neighbouring intact proteins via a sort of domino effect and thus trigger a disease. It would therefore be very useful if doctors could detect the first, still individual prions with the wrong structure. It has, however, not been possible to date to elucidate the structure of one individual biomolecule.

    In an article published in Science, a team of researchers from Stuttgart has now presented a method that can be used in the future for the reliable investigation of individual biomolecules. This is important not only for fighting diseases, but also for chemical and biochemical basic research.

    The method involves the miniaturization as it were of the nuclear magnetic resonance tomography (NMR) known from medical engineering, which is usually called MRI scanning in the medical field. NMR makes use of a special property of the atoms – their spin. In simple terms, spin can be thought of as the rotation of atomic nuclei and electrons about their own axis, turning the particles into tiny, spinning bar magnets. How these magnets behave is characteristic for each type of atom and each chemical element. Each particle thus oscillates with a specific frequency.

    In medical applications, it is normal for only one type of atom to be detected in the body – hydrogen, for example. The hydrogen content in the different tissues allows the interior of the body to be distinguished with the aid of various contrasts.

    Structural resolution at the atomic level

    When elucidating the structure of biomolecules, on the other hand, each individual atom must be determined and the structure of the biomolecule then deciphered piece by piece. The crucial aspect here is that the NMR detectors are so small that they achieve nanometre-scale resolution and are so sensitive that they can measure individual molecules exactly. It is more than four years ago that the researchers working with Jörg Wrachtrup first designed such a small NMR sensor; it did not, however, allow them to distinguish between individual atoms.

    To achieve atomic-level resolution, the researchers must be able to distinguish between the frequency signals they receive from the individual atoms of a molecule – in the same way as a radio identifies a radio station by means of its characteristic frequency. The frequencies of the signals emitted by the atoms of a protein are those frequencies at which the atomic bar magnets in the protein spin. These frequencies are very close together, as if the transmission frequencies of radio stations all tried to squeeze themselves into a very narrow bandwidth. This is the first time the researchers in Stuttgart have achieved a frequency resolution at which they can distinguish individual types of atoms.

    “We have developed the first quantum sensor that can detect the frequencies of different atoms with sufficient precision and thus resolve a molecule almost into its individual atoms,” says Jörg Wrachtrup. It is thus now possible to scan a large biomolecule, as it were. The sensor, which acts as a minute NMR antenna, is a diamond with a nitrogen atom embedded into its carbon lattice close to the surface of the crystal. The physicists call the site of the nitrogen atom the NV centre: N for nitrogen and V for vacancy, which refers to a missing electron in the diamond lattice directly adjacent to the nitrogen atom. Such an NV centre detects the nuclear spin of atoms located close to this NV centre.

    Simple yet very precise

    The spin frequency of the magnetic moment of an atom which has just been measured is transferred to the magnetic moment in the NV centre, which can be seen with a special optical microscope as a change in colour.

    The quantum sensor achieves such high sensitivity, as it can store frequency signals of an atom. One single measurement of the frequency of an atom would be too weak for the quantum sensor and possibly too noisy. The memory allows the sensor to store many frequency signals over a longer period of time, however, and thus tune itself very precisely to the oscillation frequency of an atom – in the same way as a high-quality short-wave receiver can clearly resolve radio channels which are very close to each other.

    This technology has other advantages apart from its high resolution: it operates at room temperature and, unlike other high-sensitivity NMR methods used in biochemical research, it does not require a vacuum. Moreover, these other methods generally operate close to absolute zero – minus 273.16 degrees Celsius – necessitating complex cooling with helium.

    Future field of application: brain research

    Jörg Wrachtrup sees not one but several future fields of application for his high-resolution quantum sensors. “It is conceivable that, in future, it will be possible to detect individual proteins that have undergone a noticeable change in the early stage of a disease and which have so far been overlooked.” Furthermore, Wrachtrup is collaborating with an industrial company on a slightly larger quantum sensor which could be used in the future to detect the weak magnetic fields of the brain. “We call this sensor the brain reader. We hope it will help us to decipher how the brain works – and it would be a good complement to the conventional electrical devices derived from the EEG” – the electroencephalogram. For the brain reader, Wrachtrup is already working with his industrial partner on a holder and a casing so that the device is easy to wear and to operate on a day-to-day basis. To reach this point, however, it will take at least another ten years of research.

    See the full article here .

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    The Max Planck Society is Germany’s most successful research organization. Since its establishment in 1948, no fewer than 18 Nobel laureates have emerged from the ranks of its scientists, putting it on a par with the best and most prestigious research institutions worldwide. The more than 15,000 publications each year in internationally renowned scientific journals are proof of the outstanding research work conducted at Max Planck Institutes – and many of those articles are among the most-cited publications in the relevant field.

    What is the basis of this success? The scientific attractiveness of the Max Planck Society is based on its understanding of research: Max Planck Institutes are built up solely around the world’s leading researchers. They themselves define their research subjects and are given the best working conditions, as well as free reign in selecting their staff. This is the core of the Harnack principle, which dates back to Adolph von Harnack, the first president of the Kaiser Wilhelm Society, which was established in 1911. This principle has been successfully applied for nearly one hundred years. The Max Planck Society continues the tradition of its predecessor institution with this structural principle of the person-centered research organization.

    The currently 83 Max Planck Institutes and facilities conduct basic research in the service of the general public in the natural sciences, life sciences, social sciences, and the humanities. Max Planck Institutes focus on research fields that are particularly innovative, or that are especially demanding in terms of funding or time requirements. And their research spectrum is continually evolving: new institutes are established to find answers to seminal, forward-looking scientific questions, while others are closed when, for example, their research field has been widely established at universities. This continuous renewal preserves the scope the Max Planck Society needs to react quickly to pioneering scientific developments.

  • richardmitnick 1:12 pm on December 19, 2015 Permalink | Reply
    Tags: , , NMR/MRI technology improvements   

    From LBL: “News Center Diamonds May Be the Key to Future NMR/MRI Technologies” 

    Berkeley Logo

    Berkeley Lab

    December 16, 2015
    Lynn Yarris (510) 486-5375

    Berkeley Lab/UC Berkeley Researchers Increase NMR/MRI Sensitivity through Hyperpolarization of Nuclei in Diamond

    The research group of Alex Pines has recorded the first bulk room-temperature NMR hyperpolarization of carbon-13 nuclei in diamond in situ at arbitrary magnetic fields and crystal orientations. (Photo by Christophoros Vassiliou)

    Researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have demonstrated that diamonds may hold the key to the future for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) technologies

    In a study led by Alexander Pines, a senior faculty scientist with Berkeley Lab’s Materials Sciences Division and UC Berkeley’s Glenn T. Seaborg Professor of Chemistry, researchers recorded the first bulk room-temperature NMR hyperpolarization ​of carbon-13 nuclei in diamond in situ at arbitrary magnetic fields and crystal orientations. The signal of the hyperpolarized carbon-13 spins showed an enhancement of NMR/MRI signal sensitivity by many orders of magnitude above what is ordinarily possible with conventional NMR/MRI magnets at room temperature. Furthermore, this hyperpolarization was achieved with microwaves, rather than relying on precise magnetic fields for hyperpolarization transfer.

    Pines is the corresponding author of a paper in Nature Communications describing this study. The paper is titled Room-temperature in situ nuclear spin hyperpolarization from optically pumped nitrogen vacancy centers in diamond.

    Jonathan King, a member of Pines’ research group is the lead author. Other co-authors are Keunhong Jeong, Christophoros Vassiliou, Chang Shin, Ralph Page, Claudia Avalos and Hai-Jing Wang.

    (From left) Claudia Avalos, Keunhong Jeong and Jonathan King were part of a team led by Alex Pines that used microwaves to enhance NMR/MRI signal sensitivity many orders of magnitude above what is ordinarily possible with conventional NMR/MRI magnets at room temperature. (Photo by Roy Kaltschmidt)

    The authors report the observation of a bulk nuclear spin polarization of six-percent, which is an NMR signal enhancement of approximately 170,000 times over thermal equilibrium. The signal of the hyperpolarized spins was detected in situ with a standard NMR probe without the need for sample shuttling or precise crystal orientation. The authors believe this new hyperpolarization technique should enable orders of magnitude sensitivity enhancement for NMR studies of solids and liquids under ambient conditions.

    “Our results in this study represent an NMR signal enhancement equivalent to that achieved in the pioneering experiments of Lucio Frydman and coworkers at the Weizmann Institute of Science, but using microwave-induced dynamic nuclear hyperpolarization in diamonds without the need for precise control over magnetic field and crystal alignment,” Pines says. “Room-temperature hyperpolarized diamonds open the possibility of NMR/MRI polarization transfer to arbitrary samples from an inert, non-toxic and easily separated source, a long sought-after goal of contemporary NMR/MRI technologies.”

    “These results are an important contribution that adds to a growing arsenal of tools being developed by experts throughout the world, including leading laboratories in the US, Europe, Japan and Israel, for creating a more sensitive NMR/MRI signature at easily attainable conditions,” says Frydman, a professor of chemistry at thes Weizmann Institute of Science. which is located in Israel, near Tel Aviv. “Achieving this could open up a plethora of applications in physics, chemistry and biology.”

    The combination of chemical specificity and non-destructive nature has made NMR and MRI indispensable technologies for a broad range of fields, including chemistry, materials, biology and medicine. However, sensitivity issues have remained a persistent challenge. NMR/MRI signals are based on an intrinsic quantum property of electrons and atomic nuclei called spin. Electrons and nuclei can act like tiny bar magnets with a spin that is assigned a directional state of either “up” or “down.” NMR/MRI signals depend upon a majority of nuclear spins being polarized to point in one direction – the greater the polarization, the stronger the signal. Over several decades Pines and members of his research group have developed numerous ways to hyperpolarize the spins of atomic nuclei. Their focus over the past two years has been on diamond crystals and an impurity called a nitrogen-vacancy (NV) center, in which optical and spin degrees of freedom are coupled.


    “An NV center is created when two adjacent carbon atoms in the lattice of a pure diamond crystal are removed from the lattice leaving two gaps, one of which is filled with a nitrogen atom, and one of which remains vacant,” Pines explains. “This leaves unbound electrons in the center between the nitrogen atom and a vacancy that give rise to unique and well-defined electron spin polarization states.”

    In earlier studies, Pines and his group demonstrated that a low-strength magnetic field could be used to transfer NV center electron spin polarization to nearby carbon-13 nuclei, resulting in hyperpolarized nuclei. This spin transference process – called dynamic nuclear polarization – had been used before to enhance NMR signals, but always in the presence of high-strength magnetic fields and cryogenic temperatures. Pines and his group eliminated these requirements by placing a permanent magnet near the diamond.

    “In our new study we’re using microwaves to match the energy between electrons and carbon-13 nuclei rather than a magnetic field, which removes some difficult restrictions on the strength and alignment of the magnetic field and makes our technique more easy to use,” says King. “Also, in our previous studies, we inferred the presence of nuclear polarization indirectly through optical measurements because we weren’t able to test if the bulk sample was polarized or just the nuclei that were very close to the NV centers. By eliminating the need for even a weak magnetic field, we’re now able to make direct measurements of the bulk sample with NMR.”

    In their Nature Communications paper, Pines, King and the other co-authors say that hyperpolarized diamonds, which can be efficiently integrated into existing fabrication techniques to create high surface area diamond devices, should provide a general platform for polarization transfer.

    “We envision highly enhanced NMR of liquids and solids using existing polarization transfer techniques, such as cross-polarization in solids and cross-relaxation in liquids, or direct dynamic nuclear polarization to outside nuclei from NV centers,” King says, noting that such transfer of polarization to solid surface and liquids had been previously demonstrated by the Pines group using laser polarized Xe-129. “Our hyperpolarization technique based on optically polarized NV centers is far more robust and efficient and should be applicable to arbitrary target molecules, including biological systems that must be maintained at near ambient conditions.”

    This research was supported by the DOE Office of Science.

    See the full article here .

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