Screen needle screening

The atom probe field-ion microscope (APFIM) and its subsequent developments, the position-sensitive atom probe (POSAP) and the pulsed laser atom probe (PLAP), have the ultimate sensitivity in compositional analysis (i.e. single atoms). FIM is purely an imaging technique in which the specimen in the form of a needle with a very fine point (radius 10-100 nm) is at low temperature (liquid nitrogen or helium) and surrounded by a noble gas (He, Ne, or Ar) at 10 -10 Pa. A fluorescent screen or a... 

Pickett SD, Sherborne BS, Wilkinson T, Bennett J, Borkakoti N, Broadhurst M, Hurst D, Kilford I, McKinnell M, Jones PS. Discovery of novel low molecular weight inhibitors of IMPDH via virtual needle screening. Bioorg Med Chem Lett 2003 13 1691-4. 

Muller (1951, 1956) developed this instrument, which for the first time enabled extensive details of the atomic structure of a solid surface to be seen directly. Figure 1.1 illustrates schematically the basic construction of a FIM. The specimen is prepared in the form of a fine wire or needle, which has been chemically or electrochemically polished to a sharp point with an end radius typically 50-100 nm. It is mounted along the axis of a vacuum chamber, about 50 mm from a phosphor screen (perhaps 75 mm in diameter). The specimen is mounted on an electrical insulator within a cryostat, and it can be raised to a high positive potential (3-30 kV) by means of the leads attached. 

Fig. 19.3 Flow chart of 3D structure-based biased needle screening as applied to the bacterial enzyme, gyrase.

Pickett, S.D., Sherborne, B.S., Wilkinson, T., Bennett, )., and Borkakoti, N. Discovery of low molecular weight inhibitors ofIMPDH Via virtual needle screening. Bioorg. 

Boehm, H.J., Boehringer, M., Bur, D., Gmuender, H., Huber, W., Klaus, W., Kostrewa, D., Kuehne, H., Luebbers, T., Meunier-Keller, N., and Mueller, F. Novel inhibitors of DNAgyrase 3D structure based biased needle screening, hit validation by biophysical methods,... 

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