One of the long sought objectives in science has been to watch atomic motions on the primary timescales governing structural transitions. From a chemistry perspective, this capability would give a direct observation of reaction forces and probe the central unifying concept of transition states that links chemistry to biology. To achieve this objective, there are not only extraordinary requirements for simultaneous spatial-temporal resolution but equally important, due to sample limitations, also one on source brightness. With the development of ultrabright electrons capable of literally lighting up atomic motions, this experiment has been realized (Siwick et al, Science 2003) and efforts accelerated with the onset of XFELs (Miller, Science 2014). The table top ultrabright electron sources developed at the University of Toronto have achieved the fundamental space-time limit to imaging chemistry (Li et al, ACS Photonics 2020). This source technology has been further advanced to enable high throughput structure determination based on Serial Nano-Electron Diffraction (Serial NED). This method holds promise as a table top equivalent to an XFEL requiring orders of magnitude less material requirements to further enhance throughput and the prospect of true “Lab-on-a-Chip” synthetic approaches and screening approaches.
A number of fully atomically resolved chemical reactions will be discussed. These studies have discovered the “magic of chemistry”, which leads to an enormous reduction in dimensionality at barrier crossing regions that ultimately makes chemical concepts transferrable from one molecular moeity to another and allows scaling in complexity all the way to living systems. Given the enormous complexity in terms of coupled chemical reactions driving biological processs within cells, there must be a similar reduction principle at play albeit in the form of spatial correlations in free energy. The same technology developed to directly observe atomic motions can be adapted to next generation spatial imaging modalities, along with correlative imaging, to directly map the chemical driving forces of the cell. This prospect promises to fill in the gaps between genetic information and protein expression, from the blue print to the actual execution of the code. The specific technological requirements under development to acheive this Moonshot for Biology and their potential spin off applications will be discussed as part of proposal for a strategic iniative to map the cell.

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