In-Situ Transmission Electron Microscope Liquid Specimen Holder with Integrated Temperature and Acidity Sensors

This SBIR Phase I project will develop a microfluidic in-situ TEM specimen holder with accurate environmental parameter monitoring capabilities; The inability to dynamically image materials at atomic resolutions in changing liquid environments is a significant impediment to the advancement of physical, chemical, materials, biological and medical sciences. Currently, none of the results acquired with Hummingbirds continuous flow fluid sample holders can be quantified or verified because it is not possible in the current system to directly locally measure the environmental parameters in the microfluidic cell; specifically temperature and pH. This proposal will aim to completely solve the environmental parameter measurement and control issues by developing a new in-situ TEM microfluidic holder that contains an integrated microfabricated local temperature sensor and a pH sensor. This will be a crucial enabling technique for opening up the possibilities of in-situ experiments in liquids where for electrochemical processes the local (change in) concentration of acids and bases at the sample are key reaction parameters. The broader impact/commercial potential of this project is the availability of a characterization technique that can image solid/liquid interfaces up to atomic resolution under quantifiable and accurately controllable environmental conditions. This will provide new insights into the process controlling assembly and, ultimately, function in biological systems and biomolecular materials. The interface between macromolecular and inorganic components is a hallmark of these materials. In many cases, the organic side of the interface plays an active role in directing the formation and organization of the inorganic materials. In others, the inorganic component is the substrate that modulates macromolecular assembly. Our understanding of either case is limited because, until recently, we lacked an experimental tool possessing both the spatial and temporal resolution needed to capture the formative events. While in situ TEM has emerged as an enabling capability in this regard, to develop a predictive understanding that can impact biomedical and materials technologies, we require an environment in which temperature and pH are tightly controlled. This new window into biomolecular materials promises dramatic advances in our understanding of the underlying thermodynamic and kinetic factors that lead to self-organization of macromolecules and that drive formation of inorganic nanostructures at the macromolecular-inorganic interface.