Further information relating to the D19 detector array proposal

V.T. Forsyth and S.A. Mason

The proposed  new large detector array to replace the banana detector currently used on D19 will produce a gain of a factor of 25 in solid angle. This supplement to the original proposal emphasises the huge gains that will follow from this development for both single crystal work, and for fibre diffraction studies of biological and industrial polymers. Such gains offer exciting new opportunities in chemistry, physics and biology as well as enabling much better experiments for problems that are currently studied. We present compelling evidence from the literature and from the user community that attests to the quality of the work that has been carried out on D19 in its current form and of the impact that the proposed development will have for the future.

The case for the major upgrade planned on the D19 diffractometer has been given in detail (Forsyth & Mason, April 1999). The plan to install the new detector system is not one that can simply be said to offer “more of the same but better”. A gain of a factor of 25 in effective detecting solid angle is a very significant step forward and one that will open up entirely new project areas in single crystal and fibre diffraction. However, it will also undoubtedly mean that experiments of the type that are currently undertaken will be carried out both a great deal better and a great deal more quickly. It is indeed the plan that in addition to new problems that cannot be tackled using the current system, the new instrument will become much more competitive in existing areas for which there is strong demand to carry out projects of high scientific interest. In general terms we see the development as one that is also necessary to maintain the competitive edge that the ILL has in this area and one that stands easily on its own merits.

D19 is currently the only instrument in the world that is capable of carrying out high-angle neutron fibre diffraction measurements, and its work in this area has been very favourably reviewed (see for example Stubbs, 1999, which specifically highlights publications arising from D19 work that are tagged as “of special interest” and “outstanding interest”; see also Niimura, 1999) Such studies have provided important information on the location of water molecules or of hydrogen atoms in biological polymers such as DNA (water is a key determinant of DNA structure), cellulose (hydrogen bonding plays a vital role in determining its unique physical properties), hyaluronic acid, and filamentous viruses. More recently work has started in collaboration with industry on the use of neutron fibre diffraction in the investigation of the physical properties of industrial polymers such as the poly aryl ether ketone compounds (eg PEEK, PEKK and related high-performance thermoplastics), analogues of Nylon 66, and Kevlarã. The expanding interest in structural studies of biological and industrial polymers (as evidenced by current trends in x-ray diffraction work) and the key aspects of hydration and hydrogen bonding (totally inaccessible to x-ray fibre diffraction but nonetheless having a vital bearing on biological function or physical properties), are opening up important new opportunities for neutron fibre diffraction.

The new D19 instrument will mean that for the first time detailed measurements will be possible of continuous diffraction from polymer molecules. Such diffraction predominates in diffraction studies of many filamentous viruses, drug-DNA and protein-DNA complexes. It is also a key aspect of changes in ordering that occur during structural transitions. The new instrument will also mean that it will be possible to use D19 to study samples that have hitherto been far too small to study using neutrons.

Half of the beam time requests for D19 concern chemical crystallography, the other half being divided between biological structure (including fibre diffraction) and physics and materials science.  Thus more than half of D19’s time is used for studies of single crystals with thermal neutrons: D19 is needed when the unit cell is large, or samples are small. There is a consistently strong demand from users with inorganic or organic systems with 100-200 atoms per asymmetric unit, and crystals of only a few mm3. Usually the aim is to find accurate positional and anisotropic displacement parameters for atoms not found with adequate precision by X-rays: it is the user who decides that neutrons are needed. The proposals are consistently rated highly by the sub-committees, but users often produce crystals smaller than needed: this leads either  to abandoned experiments or to structural refinements with e.g. only isotropic displacement parameters. Letters of support received for D19 from very experienced single-crystal users of both neutrons and X-rays emphasise that modern X-ray instruments, whether on laboratory sources or at synchrotrons, all have 2-D position-sensitive detectors, and that this has led to not just a quantitative but a qualitative change in the science done.

The technical aspects of the project have been covered in detailed studies at the ILL by Mason, Langan, & Walsh (see Forsyth & Mason, April 1999 for details). The design of the new detector bank is modular so that in the event of the failure of one detector module, replacement will be straightforward without great disruption to the user programme. The detector technology that is being developed at the ILL is the microstrip system - these detectors were easily integrated into the D19 design. We urge that the ILL gives the development of these detectors the highest priority and argue that (a) it is absurd to hold back on detector provision when the notional cost of beam time is by comparison high, and (b) the D19 project can be used to propel the development of 2-dimensional position sensitive detectors, provided that the detector group is sufficiently resourced (at present it is not). Such development will clearly benefit many other instruments at the ILL. We are making a case that, while being sharply focussed on D19, has clear benefits to a much wider section of the neutron user community.  Several generations of 5-year scientists have made good use of the D19 banana detector – built in the early 1980’s – but there is increasing frustration with the lack of investment.  Subcommittees 5 and 8 have repeatedly regretted that it was not possible to give adequate beam-time allocations for the most difficult experiments, and asked for a larger detection area for D19, most recently 5a chairman Michel Latroche, October 1999 “ the upgrade of D19 with a 2-D detector is still strongly wanted  by people from the single crystal diffraction field” .  Highly qualified users such as Christoph Kratky (former chairman of subcommittee 8) have expressed  more than surprise that d19 has not been upgraded; the ILL Scientific Council 1998 review  of single crystal instruments came to the same conclusion. The opportunities that face us here have not been overlooked by competing neutron sources, and that it would be tragic for the ILL to lose its grip on an area where it has made unique and pioneering contributions.

 

References

Forsyth, V.T. & Mason, S.A., The Millennium Programme – proposals for ILL’s 5-year development programme, pg 47-50 (April 1999). (Also at http://www.ill.fr/dif/2000/2000-D19.html ).

G. Stubbs, Current Opinions in Structural Biology  9, 615-619 (1999).

N. Niimura, Current Opinions in Structural Biology 9, 602-608 (1999).

 

Feedback from the scientific & user community on the impact of D19 in its current form and on the proposed development (full documents available on request)

Professor A. Watts, Dept. Biochemistry, Oxford University. Chairman of the BBSRC Neutron Allocation Panel and Director of the National Biological Solid State NMR facility, RAL, Didcot, UK:

“…D19 has enjoyed a world wide reputation over some years, and if ILL is to stay at the fore-front of such methodology, it must be permitted to evolve and develop. …project will have major benefits, not only in the enhancement in the detection levels of diffracted neutrons but also in increasing the detected solid angle (both of which are vital in biological applications). The ability to measure continuous diffraction, to examine crystalline material and to measure from small samples that for a variety of possible reasons cannot be made larger (probably controlled by the biological), are all vital in biology (with) neutrons…”

Professor W. Saenger, Head, Institut fuer Kristallographie, Freie Universitaet Berlin, former editor Acta Crystallographica, and D19 user:

“…the data collection time will be reduced dramatically… important for crystals with very large unit cell constants as found in larger carbohydrates,  proteins and nucleic acids … also allow to use much smaller crystals for data collection than is possible at present… a larger detector on D19 will permit to enter new fields in structure research. It will widen our knowledge considerably beyond the information available from data collected with synchrotron radiation, especially if the possibilities associated with isotope exchanges are considered.”

Professor H. Chanzy, Director of Research at CNRS and D19 user:

“…The instrument has been very reliable and well designed for the purpose of our experiments …It is my opinion that the diffractometer at D19 would be vastly improved if the size of the detector could be enlarged to cover a much larger angular range. This would allow to cut down the recording time, this cutting might even reach a factor of 20. Also, with a wider detector, one could think of using much smaller samples: this would expand dramatically the availability of D19 to the biological field where small samples are normally the rule. Indeed, neutrons are evolving as a very important tool for biology and D19 is one of the key instruments for biologists and biophysicists.”

Professor J.A.K. Howard, Dept. of Chemistry, University of Durham, UK, former Chairman of Subcommitee 5a, and D19 user:

“Like many Users of D19, I don't need reminding that these upgrades have been 'in the wings' and 'promised' for a long time and they are most certainly overdue. The instrument would be infinitely more useful to a wider range of chemists and biologists, if the detector bank is improved and increased. …reductions in time taken , are of great interest to the chemical community, who are innately impatient about waiting for answers …  over months and sometimes years taken to grow crystals and collect data.   It is frustrating also, especially after a long wait, if we then only can refine the limited data with an isotropic model.”

Professor W. Fuller, Dept. of Physics, Keele University, former Chaiman of Subcommittee 8, and D19 user:

 “The work on DNA hydration…at the ILL has been highlighted in reviews and Annual Reports and is generally regarded as opening up an important new area of applications on D19 for the characterisation of partially ordered materials.  However for this exciting potential to be achieved it will be crucial to have a genuinely 2-dimensional detector.  Because of the nature of the order in fibrous polymers this will allow the time required for the collection of diffraction data to be reduced by more than a factor of 10.  Not only will this gain allow a much wider range of materials to be studied but even more importantly it will allow the characterisation of structural variation across polymer materials with a gain of ~10 in spatial resolution. …D19 is already the best instrument for neutron fibre diffraction in the world.  This enhancement would ensure that this lead was maintained for many more years.”

Professor M. de Boissieu, Chargé de recherche au CNRS, Grenoble, and D19 user:

“…open new fields of research…. This will be helpful … for the study of incommensurate and quasicrystalline phases. …these materials are characterised by a dense set of Bragg reflections, with a large dynamical range, i.e. there are a large number of weak reflections. A proper data collection requires a systematic scan of reciprocal space …The high speed of the detector array will also make feasible the study of phase transitions in quasiperiodic and incommensurate systems. The understanding of the mechanism of these phase transition requires the measure of a large number of reflections as a function of the temperature”

Professor R. Bau, Dept. of Chemistry, University of Southern California, Los Angeles, USA, and D19 user:

“…really excited to hear that I.L.L. is planning to install a new detector array at D-19, with a much larger detector solid angle.… we have successfully grown large crystals of the small protein rubredoxin, and are interested in collecting a high-resolution neutron data set in order to map out the hydrogen-bonding pattern in the molecule.  It would be nice to carry out this data collection at the D-19 diffractometer because of its superb cryogenic capabilities…. With the new detector array …this project becomes possible. … neutron structural studies of biologically important molecules represent the "wave of the future" for neutron diffraction, but in order to make a substantial impact we have to make the technique feasible in terms of data collection times ….”

 

Prof. Alberto Albinati, University of Milano, Institute of Pharmaceutical Chemistry, and D19 user:

“In the field of transition metal hydrides, many compounds that are reaction intermediates and important for the understanding of the reaction mechanisms are difficult to isolate and, often, unstable in solution and thus it is not possible to grow single crystals the size presently required for neutron data collection. Moreover these complexes usually contain bulky ligands resulting in big unit cells that require D19 type instruments and rule out the use of TOF methods. …We have shown that in determining the coordination geometry of transition metal hydrides the X-ray diffraction may be completely misleading; moreover these molecules may be too big for reliable theoretical predictions of their shapes and therefore neutron diffraction is the only structural technique capable of unambiguous answers…. It should be noted that, after the permanent shut down of the HFBR reactor in Brookhaven, D19 is (with the exception of 2 four circle machines at the Oak Ridge Laboratory) the only high resolution single crystal diffractometer on a high flux beam line.”

 

Dr. D.A Marvin, Dept. of Biochemistry, Cambridge University, and D19 user:

“…D19 is unique in the world, and our work has shown that it is feasible to collect continuous transform fibre diffraction data, albeit very slowly… one can use neutron diffraction with specific D/H labelling to detect the position of side chains, something that is only feasible in rare cases with x-ray diffraction and heavy atoms. With the relatively low-resolution data that one gets from fibre diffraction, this kind of D/H labelling will often be a crucial factor in determining the structure. …As you will remember, we needed to make a bundle of fibres, and it is a matter of luck as well as skill to induce the individual fibres to lie parallel in the bundle. The new detector would also make it feasible to look at smaller samples. “

 

 



This type of diffraction occurs where molecules that are lined up in a parallel array (as in a fibre) have an essentially random axial relationship to one another, and do not form a completely crystalline system. The consequence is that in all reciprocal lattice zones apart from the one that corresponds to the “birds eye view” along the axes of the filaments, the intensity that would normally be concentrated into strong crystalline reflections is spread out along layer lines in reciprocal space, giving continuous diffraction that on a point for point basis is much weaker by perhaps an order of magnitude. The data are however very well defined and offer a wealth of information that is not limited to localised regions of reciprocal space at reciprocal lattice points.

 

A very recent experiment at 20K on d19 by Wolfram Saenger and Olaf Nimz on a completely new cyclodextrin (called “CA10” with 10 glucose residues in a large ring to form a boat-shaped molecule, and complexing many water molecules), on a very small undeuterated crystal of only 0.14 mm3, unit cell  4874Å3, is a good example of what is and is not possible on the present D19. All water molecules could be refined, and the disorder of one of the important hydroxyl positions could be seen. But with only 2558 unique reflections measured in 20 days of beam time, only about 620 parameters could be refined.  Other such difficult experiments are either not proposed, or fail. With better detectors, a full anisotropic refinement would be possible in much less time, leading to more reliable chemical conclusions. Note that the basic structure had been determined from synchrotron X-rays, but that the users judged, correctly in this case, that neutron diffraction would give key new information.