By Lutz HM Bruegemann, A Kern, Bob B He and Uwe Preckwinkel of Bruker Advanced X-ray Solutions, Madison, Wisconsin, USA and Karlsruhe, Germany.

Parallel synthesis by means of combinatorial approaches and high-throughput screening techniques are of high relevance in areas such as catalyst development and drug discovery. Among other analytical methods, such as IR- or Raman-spectroscopy, X -ray diffraction potentially offers the most unambiguous way to identify the structural characterisation of any solid form. This is due to the following strengths:

  • The penetrating power of the X-rays into the material
  • X-rays are nondestructive to the samples 1,2
  • The data collection time is short
  • The ability to unequivocally differentiate one crystallographic phase from the other

If using XRD 2, the structural information of a material library can be obtained with high speed and high accuracy 3-6

HTS by XRD 2

An XRD 2 system consists of a high-brilliant X-ray source (see Figure 1), a 2-dimensional detector, a sample stage and computer control and data evaluation software. The typical weakly-scattered materials are examined in reflection or transmission geometry. The D8 DISCOVER with GADDS for combinatorial screening transmission (see Figure 2) is designed to exactly meet all demands for rapid XRD screening.

The detector features real-time data collection in a large area of a diffraction pattern, high sensitivity, and low background. The outstanding benefits of XRD 2 are that it is a non-destructive technique and a minimum effort of sample preparation is required.

A portion of the X-ray beam passing an individual spot of a material library is diffracted into the 2D detector. The specific material properties are coded in the angular position, taking in the details of the shape and symmetry, along with the intensity distribution of the measured XRD 2 pattern.

Automatic mapping and data evaluation

From an XRD 2 pattern, we can derive information about crystalline phase, polymorphism, crystallinity precentages, particle size and shape, preferred orientation and strain. A lmost all of these parameters can be used for the screening of material libraries. The data collection is automatically scanned over all the spots in the material library. The screening results can be visualised by PolySNAP 8-9 software as a colour-coded cell display, dendrogram, 3D plot, or a pass/fail map with user-defined criteria (see Figure 3).
HTS by means of X-ray diffraction is one of the most sensible methods for combinatorial chemistry or drug discovery, due to the facts being non-destructive and requiring no sample preparation. The described XRD 2 system is designed for high-throughput screening, using the latest analytical technologies and innovative software tools to perform easy-to-use screening on a wide variety of analytical parameters.

Footnotes

1. BB He, U Preckwinkel and KL Smith, Advances in X-ray Analysis, Vo. 43, 1999
2. Jens Lein, et al, Angew Chem, Int Ed Engl 1998, 37, 3369
3. B B He, et al, World Pharmaceutical Frontiers CD, 2002
4. Philip R Rudolf and Brian G Landes, Two-dimensional X-ray Diffraction and Scattering of Microcrystalline and Polymeric Materials, Spectroscopy, 9(6), pp 22-33, July/August 1994
5. SN Sulyanov, AN Popov and DM Kheiker, Using a Two-dimensional Detector for X-ray Powder Diffractometry, J. Appl Cryst. 27, pp 934-942, 1994
6. L Bruegemann, et al, World Pharmaceutical Frontiers CD, 2004
7. M Davidovich, et al, European Pharmaceutical Review, 2004
8. G Barr, et al, Applied Crystallography, 2004
9. CJ Gilmore, et al, Applied Crystallography, 2004
* patent US 6,859,520 B2