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The crucial physical and technological issues pertaining to the holographic imaging of biological structures with a short-pulse, high-intensity, high-quantum-energy laser were examined. The limitations of x-ray optics are discussed. Alternative holographic techniques were considered, and it was concluded that far-field Fresnel transform holography (Fraunhofer holography) using a photoresist recording surface is most tractable with near term technology. The hydrodynamic expansion of inhomogeneities within the specimen is discussed. It is shown that expansion is the major source of image blurring. Analytic expressions were derived for the explosion of protein concentrations in an x-ray transparent cytoplasm, compared with numerical calculations, and corrections derived to account for the competitive transport processes by which these inhomogeneities lose energy. It is concluded that for the near term Fresnel transform holography, particularly, far-field or Fraunhofer holography, is more practical than Fourier transform holography. Of the alternative fine grain recording media for use with Fresnel transform holography, a photo-resist is most attractive. For best resolution, exposure times must be limited to a few picoseconds, and this calls for investigation of mechanisms to shutter the laser or gate the recording surface. The best contrast ratio between the nitrogen-bearing polymers (protein and the nucleic acids) and water is between more » the K-edges of oxygen and nitrogen. « less

High-intensity x-ray holography: an approach to high-resolution snapshot imaging of biological specimens