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NEUTRONS IN BIOLOGY
NOVA Scientific, as the first organization to develop and introduce neutron-sensitive microchannel plate detectors, is engaged in expanding the range of application areas in neutron-based research - with structural biology and biological physics providing very attractive and highly fertile ground. Indeed, neutron methods are rapidly emerging as powerful tools to elucidate information about the structure and dynamics of biological systems - which in many cases cannot be obtained with more established and conventional tools such as X-ray or electron diffraction, NMR spectroscopy, optical and fluorescence microscopy, and other techniques. These latter tools more typically probe only superficial layers, whereas neutrons have an advantage in also probing deeply into the sample volume or bulk.
As an example, changes in neutron energy and momentum, when scattered at small angles from proteins, macromolecular crystal lattices, or membranes, can yield structural details simply not available using other methods. The respective deBroglie wavelengths of cold and thermal neutron beams, of >4Å and 2Å, with negligible absorption in biological materials, correspond to atomic spacings and fluctuation amplitudes as well as energies that are well-suited to typical excitation energies in biological samples.
Neutrons vs. X-rays
Overshadowed in the past by x-ray methods such as SAXS (small-angle X-ray scattering) and X-ray diffraction, analogous neutron methods such as SANS (small-angle neutron scattering) and neutron protein crystallography, offer a number of compelling advantages for the study of biomolecular structure and dynamics. As with other areas of science, information gathered through both neutron and X-ray probes can be highly complementary and reinforcing, where non-overlapping data sets can be compared and contrasted. For example, hydrogen as well as hydration patterns in proteins and other macromolecules can be studied, which is not possible using X-rays. Macromolecular neutron crystallography, requiring a neutron wavelength bandwith of ~10-2 nm, is an example of a powerful neutron tool exploiting Laue diffraction, where the outstanding timing resolution of NOVA's neutron-sensitive detector systems can play a critical role.
Importantly, neutron probes can be quite nondestructive, as they interact very weakly with matter. Even complex or delicate biological materials can be studied in a way not possible with other forms of radiation, which may seem surprising to some. For example, X-rays can cause radiation damage in the form of changes in metal oxidation state and consequent hydrogen loss, whereas this need not occur when neutrons are used. Even in vivo studies are now being carried out using neutron probes, an area which has great potential for further development and application in medical research.
It is generally surprising that many biological and medical research scientists are unfamiliar with the power that neutrons could potentially bring to their work. In the current dramatically expanding and self-reinforcing growth era in experimental medicine and biology, the number of new biological problems requiring study and solution is starting to become nearly overwhelming. As another example, neutron studies have even been carried out in the area of neurobiology, specifically neurodegenerative disease, using model membranes and neutron reflectometry, for example at NIST's Center for Neutron Research (NCNR).
NOVA has historically maintained with NIST, a long, highly collaborative and fruitful interaction in carrying out neutron experiments at NCNR. There, cold neutrons (>4Å) are used to study structure and interactions of cell membranes and their components. For example, a SANS study investigated amyloid beta protein assemblies on a nm length scale, where are involved in Alzheimer's disease. Still another illustration of the variety of applications possible with a dedicated thermal neutron beamline, is the backscattering spectrometer IN13 at the Institut Laue-Langevin in France.
Ongoing Experimental Work
Other neutron research facilities where NOVA is also actively engaged in experiments, and which are now with very active beamlines for biological studies, are:
- ISIS (Rutherford Lab, Oxford, UK)
- PSI (Paul Scherrer Institute, Switzerland)
- FRM-II Antares facility, Garching, Germany
- SNS (Spallation Neutron Source, Oak Ridge National Lab)
Please check back, as we'll be adding more information soon!
For Further Reading
Following are a few references and links to useful sites discussing neutron methods in the context of biology:
A recent book on neutron methods in biology, is "Neutron Scattering in Biology: Techniques and Applications", by J. Fitter et al, eds. (Springer Verlag, 2006)
General reviews online:
Applications of Neutrons in Biology
New sources and instrumentation for neutrons in biology
An informative example of a University of Copenhagen study at PSI, involving protein and membranes, which also illustrates the effect of deuteration on contrast is
available here.
Overview of SANS, prepared by a NIST staff member, is available here.
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