Instruments for checking physical characteristics

Description

The Francis Crick Institute (‘the Crick’) is a biomedical research institute dedicated to understanding the scientific mechanisms of living things. Its work is to understand why disease develops and to find new ways to treat, diagnose and prevent illnesses such as cancer, heart disease, stroke, infections and neuro-degenerative diseases. The Francis Crick Institute requires a high-end Mass Cytometer that incorporates the very latest technologies available in the field, to overcome the limitations posed by traditional flow cytometry (limited number of analytes and ability to resolve tagged antibodies with overlapping fluorophores). Mass cytometry is a relatively new technology that overcomes these limitations by using lanthanide-labelled antibodies to tag cells that are then measured using a mass ctytometer (also termed CyTOF). The outcome is an improved signal-to-noise ratio and little overlap of signal, enabling cells to be labelled with far greater numbers of different antibodies than conventional flow cytometry, with over 100 detection channels being feasible. The resulting multiparametric data then allows researchers to identify not only complex protein marker combinations but also pathway activation states in normal and diseased biological systems. A major new development of this technology is the addition of an imaging module, which enables highly multiplexed 1 µm resolution images of tissues (FFPE, frozen and smears of cells) of, currently, 42 proteins simultaneously. This methodology provides a major advance in imaging, specifically enabling analysis of expression and activation state of proteins and phenotyping of cells within a tissue or a tumour. It will be possible to identify all cell types within a tissue or tumour while preserving the three dimensional architecture, thus enabling a more ‘ecosystemic’ analysis of cells. Given the known complexity of disease biology this technology has the potential to be a step-change in analytical power that transforms research in this area. The purchase of this Mass Cytometer will allow Crick researchers to make best use of the collaborative facilities at the Crick towards improving human health with a particular focus on immunity and infection. Examples include identifying immune mechanisms of pathogenesis in tuberculosis, immune response to the malaria parasite, characterization host response to HIV infection and tumour microenvironment interactions. This type of equipment will enable the Crick to maintain its cutting-edge international reputation and success in this research area at the highest international level. Currently the Crick has mass spectrometry facilities within the Proteomic and Metabolomics Laboratories but this technology allows whole cells to be analysed and is a single cell complement to genomics studies as well as integrating with Histopathology. The experiments here will explore the complexities of the immune system in health and specific disease states including malaria, HIV and Toxoplasmosis. Additionally any heterogeneous biological system would benefit from an increased number of measurable parameters, for example in stem cell and developmental biology. The imaging platform would allow dissection of cell-cell interactions, tumour-host interactions and the complexity of the tissue microenvironment to be studied at 1 micron resolution. Currently the Crick does not have this capability.