Membrane Pharmacy Structure Dynamics 

Research group : Priv.Doz. Dr. Thomas Nawroth 

Neutrons and neutron scattering 


Neutron scattering
Neutron sources
Neutron instruments
Neutron detectors


Neutrons are a powerful tool for the structure investigation of macromolecules, e.g proteins, membranes, polymers and complex materials. In contrast to X-ray photons they are scattered by the atomic nucleus. The scattering power varies widely by the isotope. The energy of the radiation is usually in the milli-eV range (cold neutrons), whereas X-ray photons exhibit keV energy. As a consequence neutrons may also be used for inelastic and quasielastic scattering, which allows the detection of energy transfer processes and energy levels in a sample. Generally neutrons are required in structural biology and polymer science for:

1.  structure estimation of non-crystalline matter at high contrast, e.g. membranes from protonated lipids in D2O-buffer.
2.  distinguishing components of molecular complexes by their contrast respective to the scattering power, which is called contrast variation.
3.  detection of molecular motion in molecular complexes by time resolved neutron scattering, e.g. of liposomes with incorporated membrane protein
4.  structure investigation of sensitive macromolecular solutions with negligible radiation damage (cold neutrons).
5.  structure investigation of very large macromolecules and complexes (nanoparticles, large membrane structures).
6.  detection of energy levels and transfer by inelastic or quasielestic scattering, which is measured by "time of flight" (TOF) experiments with a pulsed beam.
7.  In material science the magnetic scattering is of wide importance (domains, grains, spin glasses).

Neutron scattering

The neutrons passing an atom are scattered in a magnetic process by spin-spin interaction. The scattering process can quantitatively be described by the Quantum Chromo Dynamics theory, QCD. Thus the scattering is sensitive to magnetic structures and spin polarization. The scattering probability per absorbed particle is about a factor of 100 (H) to 1000 (D) higher, as compared to X-ray photons (1:100,000). If no activalable metals (Cd, Gd etc.) are present in the sample, there is no radiation damage with cold neutrons (8 Angstroem wavelength = 20 K level). This and the high contrast of protonated material versus D2O makes neutron scattering powerful for structure investigation of biological and polymer samples.
Because of the spin dependence, the scattering power of hydrogen and deuterium varies by more than one order for neutrons. Thus with a biological sample the neutron beam is scattered mainly by the hydrogen entity, in contrast to X-rays, which see the electron density (mainly carbon, oxygen, nitrogen ...).  This offers a splendid opportunity of distinguishing between the components of a macromolecular complex: The scattering intensity depends on the contrast, i.e. the scattering length difference between solvent and particle. This may be choosen by varying the deuterium content in the solvent, i.e. H2O/D2O exchange, or in some case by partial deuteration of the sample, e.g. by growth of bacteria in D2O and isolation of the deuterated constituents. A similar effect can be achieved by magnetic spin polarization. If the solvent exhibits the same scattering length density (power) as one component of a complex, the scattering amplitude of this becomes zero, i.e. it is matched. Thus the component structure may be investigated by contrast variation in situ.
The contrast of protonated biological membranes and amphiphilic polymers in D2O-buffer solution is much higher, as compared to X-rays, where the contrast of lipid membranes in H2O is nearly zero. As a consequence lipid membranes (liposomes) yield at the most powerful neutron scattering beamline, the D22 instrument at the ILL, Grenoble, an intenser signal than at the best high flux synchrotrons, while the neutron small angle scattering (SANS) of a protein solution at this beamline is equivalent to X-ray small angle scattering (SAXS) at a flux of 1011 ph/s, i.e. 1% of the flux of the most powerful monochromatic X-ray beamline, the ID2A instrument at the ESRF, Grenoble. This and the lack of radiation damage with cold neutrons explains the superior role of neutron scattering in membrane structure research.

Neutron sources

Neutrons can be produced by three techniques:
- Neutrons can be produced by nuclear reactions, e.g. in a Radium/Beryllium source. The maximal flux of this technology of <1011 n/s.cm2 is too low for the structure investigation of biological specimen or polymers.
- Neutrons can be produced by nucelar fission in a conventional reactor, e.g. of  235U (1-2 excess neutrons / fission). The flux in a commerial power plant reactor of 1012 - 1013 n/s.cm2 is to small for most scientific applications. Thus special high flux reactors have been constructed, which supply a flux of 1014 - 1015 n/s.cm2 , which is required especially for the weak scattering biological specimen and polymers. The most powerful neutron source for science is the Institut Laue Langevin, ILL at Grenoble. Most applications use a permanent monochromatic neutron beam, while a pulsed beam is produced by a chopper-absorber (1 - 10% beam yield) for quasielastic or inelastic experiments (TOF).
Properties of some european neutron sources
Flux (with intruments), power
Examples of scientific use
ILL-HFR : ILL-Grenoble
1015 n/s.cm2 , 58 MW
european contract
 proteins, membranes, polymers, time-resolved scattering, TOF
FRJ-2 : IFF-FZ Jülich
1.5 x 1014 n/s.cm2 , 24 MW
 polymers, membranes, material science reflectiometr.
FRM-II : TUM Munich-Garching (under construction)
5 x 1014 n/s.cm2 
national + european
 proteins, membranes, polymers, time-resolved-scattering, TOF
PSI , Villingen
SINQ spallation neutron source
equivalent to 1014 n/s.cm2
national + european
polymers, membranes, material science

- Neutrons can be produced by a novel technique in a spallation source, which may yield a pulsed peak flux of  1018 n/s.cm2 and an avearge flux of  1015 n/s.cm2. This requires no fission reactor but a high flux high energy proton accelerator. The proton beam of typically 1000 GeV energy hits a heavy metal target. Because the absorbed energy is much higher than the nuclear binding energy, the intermediate nuclei are spread into many small fragments of short livetime and up to 100 neutrons / incoming proton. If a linear accelerator with (optional) bunch compressor synchrotron is used, the proton and neutron beams are pulsed, which is optimal for TOF and kinetic studies. Additional to the neutrons, an intense meson beam is produced, which may be used for medical applications (cancer). The European community plans to build a large european spallation source, the ESS. Small pulsed spallation sources are located in the United Kingdom and in Japon; Switzerland has reconstructued a cyclotron for a spallation source SINQ (non pulsed) recently.

Neutron instruments

Neutron detectors

In contrast to X-rays, neutrons cannot be detected directly with a gas detector or a CCD camera, because of the lack of an electric chage. Thus the neutron signal has to be converted to a secondary signal prior to detection, e.g. by a nuclear reaction, which produces a gamma photon, or by a scintillator, which is a light emitter.
- The signal of a scintillator, e.g. a Lithium glass, can be measured by a set of photomultiplier tubes (Anger camera). The spatial resolution and flux is limited by technical reasons. A further problem is the limited lifetime of the photomultiplier tubes.
- The most commonly used neutron detectors are gas detectors with BF3 or 3He as medium. The secondary gamma photon is measured as usual for X-rays (gas amplification, Geiger-Mueller principle). Many neutron scattering instruments have 2D gas-detectors of about 1 cm spatial resolution. The signal is picked up by a XY frame grid and converted by delay line and clock devices to a digital adress of the hit at the detector suface. A problem for time resolved measurements and of strong scattering specimen is the count rate limitation of the current neutron detectors (< 200,000 /s). Thus improved detectors for experiments at high flux sources are under development at the ILL.

[ MAIN PAGE "Membrane Protein Structure Dynamics" (MPSD) ]
[ Impressum-Disclaimer | News | Address | Concepts | Science | Lectures | Technology | Publications | Health-Environment-Security | Thesis | Staff]
[ Structural Biology |Membrane Proteins| BioEnergetics | Molecular Motion | ATP-Synthase | Oxygen Proteins | Membrane Structure | NanoParticles ApplicationTime-Resolution | Computing | Study-Group ]

email to:   update : 11.02.2014