Liquid Heating Holder for Transmission Electron Microscope

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The design of relevant point-of-care diagnostics, biomaterials and therapies for remineralization depend strongly on the understanding of fundamental nanoscale processes in liquid. Often, a transmission electron microscope (TEM) is required to view nanoscale phenomena, but with several limitations: extremely thin specimens, operation in vacuum, room temperature conditions, and imaging at a single point in time. This limits its ability to probe real-time dynamic processes, particularly those in liquid systems. The requested liquid flow heating TEM holder will enable real-time visualization of nanoscale processes in liquid at relevant physiological or experimental temperatures. By coupling a TEM holder with specially designed tubing to control liquid flow, and electron transparent windows with heating contacts, liquid can be encapsulated or flowed through the TEM to allow visualization of nanoscale processes in native liquid states at precisely controlled temperatures. Placing this holder within the Canadian Centre for Electron Microscopy at McMaster University enables it to it coincide with a high resolution FEI Titan TEM equipped with the necessary detectors and spectrometers for high resolution imaging and elemental characterization of the liquid specimens. This liquid flow heating holder will enable research activities across the broad interdisciplinary fields of materials science, chemistry, and engineering physics. More specifically, it will focus on the fundamental research needed for applications in (i) micro-fabricated point-of-care diagnostics devices and DNA assembly, (ii) remineralization strategies for tissues, and (iii) the development of improved materials for orthopaedic implants. In particular, it will provide a means for detailed visualization of the interfacial structure of bioconjugates, the self-assembly of DNA nanostructures, and formation and transport of calcium phosphate in solution and at interfaces. The ability to flow solutions in/out or mix in the holder will also enable structure to be determined in parallel with biological activity, and permit observation of changes in structure with exposure to enzymes, other biomolecular binding partners, biological fluids or temperature gradients. The anticipated results of these studies will provide critical new insight into the molecular mechanisms behind liquid phase phenomena including, the structure-function relationships of nanoparticle bioconjugates, calcium phosphate mineralization pathways, and DNA analyte amplification. These findings will enable the rational design of new materials or therapies that will positively impact Canadian biomedical research and health care tools. Furthermore, these findings will stimulate HQP training and Canadian economic growth in the areas of diagnostic device fabrication, and therapies for tissue regeneration and bone attachment.