Video Liquid Transmission Electron Microscopy

Lead Research Organisation: University College London
Department Name: Chemistry

Abstract

In science more than anywhere, seeing is believing. Since Galileo time and his invention of the telescope, Hook and van Leeuwenhoek and their contribution into developing the first optical microscope, scientists have always had the necessity to see objects whether these were living or not. Since these pioneering times, we have now been given a great collection of tools that allow the visualisation of matter almost imaging molecule by molecule. Transmission electron microscopy is possibly the most powerful and versatile of these tools and indeed contributed to a myriad of scientific discoveries across Chemistry, Physics, Biology and Medicine. Today, although the ultimate frontier of imaging is the ability to visualise matter when dispersed in a liquid and how this very unique environment affects molecular organisation. Among these liquid environment, water is the most critical as being the most important ingredient of life. Yet to date, no electron microscopy can be performed in a liquid sample as its functioning is associated with high vacuum conditions and hence no liquid can exist. However we have now created new materials that act as transparent holders of liquid samples to place them under an electron beam and thus image their content. This can indeed create a unique imaging platform that will allow the imaging of a large plethora of materials (including biologicals) in water (or any other liquid) without the need to remove the liquid and hence observe their structure and dynamic nature in its own environment. Moreover we propose here to exploit the liquid nature of the sample to create a combined approach where liquid samples can easily be injected into an integrated unit that will image them with resolution approaching ten times the size of the same water molecules as well as to analyse important changes such as size, structure, optical properties and chemical nature.

Planned Impact

Imaging samples in liquid state with nanometer resolution is a critical area of research. There have been over 15 Nobel Prizes associated with the development and application of microscopy (see this year Nobel prizes for Chemistry are one most recent examples of the importance that such research area holds).
Electron microscopy, in particular, is one of the few techniques that has directly enabled discoveries in Physics, Chemistry, Biology and Medicine. The ability to observe matter and moreover its molecular structures is a critical aspect of any scientific endeavours. Whether this is a taxonomical observation of complex samples or an aimed structural study to complement material synthesis and design, TEM is always being a critical part of the analytical portfolio. Moreover, expanding our electron microscopy imaging in the liquid state will enable for the first time shedding light on dynamic events to disclose important mechanistic processes associated with nanoparticle synthesis, Brownian dynamics, reactions, energy conversion and many more. We will use and implement LiquidTEM in two three specific research areas, soft nanoparticles formation and structure, nanoparticle/cell interaction, and inorganic nanoparticles synthesis /kinetics. This will have immediate impact in areas such as Soft Matter Physics, Supramolecular Chemistry, Polymer Science, Colloid Science, Nanomaterials synthesis, Catalysis, Energy Materials, Biomimetic chemistry, Biomaterials, Nanomedicine, Bionanotechnology, Synthetic Biology, Biophysics and Biochemistry. All of these are well embedded within the strategic EPSRC remits and indeed in several other areas beyond the engineering physical science including medical and biological research as well as natural and environmental sciences.
Finally we will have the unique possibility to expand electron microscopy to a completely unexplored area and indeed establish a first-of-its-kind unit that will inspire further development and very likely serve as benchmark for future facilities across the country and the world.
Such an impact is clearly beyond the scientific endeavour and will have direct and indirect societal repercussions such as improving quality of life by developing new therapeutic and diagnostic tools, contribute to the discovery of novel sustainable energy as well as to present a new powerful tool to elucidate the impact of manmade materials in the environment.

Publications

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Luo L (2019) Thermosensitive nanocomposite gel for intra-tumoral two-photon photodynamic therapy. in Journal of controlled release : official journal of the Controlled Release Society

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Scarpa E (2020) Tuning cell behavior with nanoparticle shape. in PloS one

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Williams I (2020) Diffusioosmotic and convective flows induced by a nonelectrolyte concentration gradient. in Proceedings of the National Academy of Sciences of the United States of America

 
Description We have now established a working facility for liquid-phase electron microscopy that is serving several groups from soft materials to biological structures.
Exploitation Route As a common facility we predict a strong impact of user based in UCL and beyond.
Sectors Chemicals,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Video Liquid Transmission Electron Microscopy
Amount £3,000,000 (GBP)
Funding ID EP/N010906/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 08/2019