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Biomedical subjects

V E Cosslett

Publications and source records attributed to V E Cosslett.

13 recordsLinked to original sources

Resolution and contrast in the electron microscope: an historical review.

The development of quantitative interpretation of electron micrographs, in respect of contrast as well as resolution, has followed similar lines to those in optical microscopy, though on a faster time scale. A thorough understanding of phase contrast came relatively late in both disciplines. The definition of resolution is more complicated in the case of the electron image on account of the severe effect of lens aberrations, especially spherical aberration. Experimental measurement of the performance of an electron microscope requires an operational definition of resolving power, which must include contrast considerations as well as the limitations imposed by lack of spatial and temporal coherence of the electron source. Agreement on suitable test procedures is now being reached, at least for a very thin specimen.

Animals

Progress in electron energy loss analysis for biological specimens.

Recent work, both experimental and theoretical has clarified the range of applicability, optimum conditions of operation and limits of detection of the EELS technique. Its chief use is for microanalysis of light elements (Z < 10). For heavier elements, however, it also has an important advantage over X-ray methods in requiring lower electron exposure of the specimen for given signal strength.

Electron Probe Microanalysis

Radiation damage in the high resolution electron microscopy of biological materials: a review.

Radiation damage to a biological specimen arises from a variety of interactions between the illuminating electrons and the atoms in it. The relative probabilities of these events, and the amout of energy transferred, can be calculated from basic physical theory. The microscopic damage caused in a particular specimen in given operating conditions is more difficult to predict, but it can be measured by a number of macroscopic indicators, the chief of which are loss of mass and changes in the energy loss spectrum (or electron diffraction, pattern, if any). For most biological material the observed rate of damage is such as to set a limit to the intensity of illumination, the maximum magnification and the minimum size of detail that can be made visible. Several techniques have been devised and tested for reducing the radiation sensitivity of a specimen, of which cooling to a very low temperature and encasing it in an inert medium are the most effective. If the various protective measures act cooperatively, they could increase the effective resolution of sensitive material by an order of magnitude, making possible electron microscopy of the atomic structure of, for instance, the nucleic acid bases and other macromolecules. The prospects for observing living cells at a resolution better than that of the best optical microscopes would remain very small.

Biological Products

Radiation damage in electron microscopy of organic materials: effect of low temperatures.

As measured by the life-time of their electron diffraction patterns, the radiation sensitivity of anthracene and coronene at 500 kV is reduced by a factor of three to four at liquid helium temperature in comparison to room temperature, For l-valine the ratio is about 1-8 but there is a wide variation in the results, possibly due to differences in crystal thickness. The end-dose at 20 degrees K for valine is equivalent to 13 electrons/A2; for anthracene and coronene it is about 600 electrons/A2 at room temperature. The variation of end-dose with temperature shows that at least two mechanisms must be involved in damage to such compounds, possibly concerning the breaking of intermolecular and intramolecular bonds, respectively.

Anthracenes

Contribution of electron energy loss spectroscopy to the development of analytical electron microscopy.

The combined use of an electron energy loss spectrometer and an electron microscope provides some chemical information at the nanometer scale. The physics of the interaction processes between the incident electron beam and the thin sample foil is reviewed in terms of energy and momentum transfer. This analysis of the content of an electron energy loss spectrum allows us to establish rules for a satisfactory use of the information and to discuss the detection limits of this newly developed microanalytical technique.

Electron Probe Microanalysis