Abstract: The invention relates to a method of and apparatus for preparing a sample for imaging or diffraction experiments under cryogenic conditions, comprising the steps of applying a sample to sample carrier, such as a film on a support, in particular a grid comprising such a film on a support, or removing residual medium, typically liquid, from an incubated sample on a film on a support, and vitrifying the sample. The sample is vitrified by directing a jet of liquid coolant to the center of the film and onto the sample.

Abstract: The invention relates to a method of and apparatus for preparing a sample for imaging or diffraction experiments under cryogenic conditions, comprising the steps of applying a sample to sample carrier, such as a film on a support, in particular a grid (3) comprising such a film on a support, or removing residual medium, typically liquid, from an incubated sample on a film on a support (3), and vitrifying the sample. The sample is vitrified by directing a jet (50, 51) of liquid coolant to the center of the film (3) and onto the sample.

Abstract: A micro-reactor is provided for observing small particles, cells, bacteria, viruses or protein molecules in a fluid. The micro-reactor includes a first channel for containing the fluid and a second channel adjacent to the first channel. A gap connects the first channel and the second channel and a window transparent to the method of inspection is provided at the gap. A static or dynamic gradient, such as a gradient in concentration of a chemical or biological material, in pressure, in temperature, in electric potential, or in magnetic field, is applied across the gap, thereby causing the particles to cross the gap. By detecting a property of the particles upstream in the first channel and then applying a pressure burst over the channels when the property meets certain pre-set criteria, only selected particles can be placed in the gap.

Abstract: The invention relates to a micro-reactor for observing small particles, cells, bacteria, viruses or protein molecules in a fluid. The micro-reactor shows a first channel formed between two layers for containing the fluid, with an inlet and an outlet, the two layers separated by a first distance. A likewise second channel with an inlet and an outlet is placed adjacent to the first channel. A gap connects the first channel and the second channel, at the gap at least one layer showing a window transparent to the method of inspection and at the window the two layers being separated by a very small distance of, for example, 1 ?m or less. The micro-reactor may be used with an optical microscope (in which all particles are in focus), inspection with a Scanning Transmission Electron Microscope (in which the range of the electrons is limited), inspection with soft X-rays in the 250-500 eV range (also showing a limited range), etc.

Abstract: Mycobacteria such as M. tuberculosis and M. leprae are considered to be prototypical intracellular bacilli that have evolved strategies to enable growth in the intracellular phagosomes of the host cell. By contrast, we show that lysosomes rapidly fuse with the virulent M. tuberculosis and M. leprae— containing phagosomes of human monocyte-derived dendritic cells and macrophages. After 2 days, M. tuberculosis progressively translocate from phagolysosomes into the cytosol where they replicate. Cytosolic entry is also observed for M. leprae but not for the vaccine strain, M. bovis BCG, or killed mycobacteria, and is dependent upon secretion of the mycobacterial gene products CFP-IO and ESAT-6 of the RDI region. The present invention further provides means and methods for using these findings in therapeutic and immunogenic compositions.