Cellular and sub-cellular sampling using laser capture microdissection to understand disease mechanisms (360G-Wellcome-212917_Z_18_Z)

We propose a laser microdissection microscope (LMD) system that due to its high precision and contact-free laser technology allows the quickest and safest method of microdissection to extract precisely defined samples comprising intact biomolecules. The sample preparation method allows users to define exactly where to extract tissue from within a tissue section, cultured live cells or embryonic fish larvae. After selection, the specimen is separated from the tissue or cell culture by the laser and subsequently transported into the collection device with a targeted laser pulse. The ability of LMD to select specific cells or sub-cellular structures is enhanced by using infrared laser-based optical trap and tweezers. These tools permit manipulation of cells or particles for extraction, in addition to moving cells, beads or particles in live tissues, without damage, for measuring of tissue stiffness or flow. Extracted samples are processed for downstream quantification using genomics, transcriptomics, microarrays, next generation sequencing, biochips, or proteomics. This will allow users to precisely correlate ‘upstream’ measurements such as imaging of cells or physiological readouts with molecular characterisation, something that is not available to the research community at King’s and presents a key barrier to our research goals.