Mapping Atomic Motions with Ultrabright Electrons: Towards Making a Molecular Map of the Cell


R. J. Dwayne Miller1. Max Planck Institute for the Structure and Dynamics of Matter, Luruper Chaussee 149, Hamburg 27761, Germany
2. Departments of Chemistry and Physics, 80 St. George Street, University of Toronto, Toronto, Ontario M5S 3H6, Canada

The first atomic view of strongly driven phase transitions (Siwick et al, Science 2003) illustrated the mechanism to control nucleation growth to nm scales (10 atoms/molecules).  To take advantage of this new insight, a laser concept was developed based on a seeded Optical Parametric Amplifier and microchip laser technology to provide a compact robust source engineered to excite the OH stretch of water in biological tissue for use in laser surgery.  It was discovered that this new mechanism ejects entire proteins into the gas phase intact, and most importantly the damage to surrounding tissue was negligible, with no scar tissue formation (Amini-Nik et al, PLoS 2010).  This is the first method, by any means, capable of surgery without scar tissue formation.  The long held promise of the laser for achieving the fundamental (cell) limit to surgery has now been realized.  In the process, it was also discovered that entire proteins, even protein complexes, are ejected into the gas phase intact, with the whole process of vibrational excitation, coupling to translational motion,  and ablation, occurring faster than even collisional exchange of the excited water with the proteins (Ren et al Nanotech 2015).   This new laser ablation mechanism referred to as Desorption by Impulsive Vibrational Excitation (DIVE) provides a new means for in situ spatial mapping with mass spectroscopy in which very detailed molecular signatures of different tissue types have been observed.  An imaging mass spectrometer is being designed based on the technology from the group’s high brightness electron source development, which should be capable of near single molecule detection efficiency, to approach the single molecule detection limit in analytical chemistry without labeling.  The physics is now in place to achieve sufficient sensitivity and spatial resolution to literally make a molecular map of the cell.  This level of information is key to unlocking the mysteries of cell differentiation and overall biochemical pathways leading to specific cell functions.  The basic theory for the laser ablation process, the first steps in applications for mass spectroscopy as feedback in laser surgery, and towards the forementioned fundamental limits in spatial mapping and biodiagnostics, will be discussed.

R. J. Dwayne Miller

R. J. Dwayne Miller has published over 200 research articles, one book, and several reviews. He has pioneered the development of both coherent multidimensional spectroscopy methods, associated ultrafast laser technology, and introduced the  concept of using ultrabright electron sources to probe structural dynamics.  The electron sources developed by his group are sufficiently bright to literally light up atomic motions in real time. He and his group were the first to capture atomic motions during the defining moments of chemistry – to directly observe the very essence of chemistry. This work accomplished one of the dream experiments in science, to bring the chemists’ collective gedanken experiment of chemistry to direct observation.   

R. J. Dwayne Miller has trained more than 60 PhD/Postdoctoral students, with former students currently holding faculty or senior scientist positions at Yale, Michigan (2), Kaiserslautern, NIST, Lawrence Livermore National Labs, Fritz Haber Institute, McGill, U Waterloo, U Tokyo, Tokyo Tech, Harvard, U Toronto, as representative examples. His group has also started up 6 companies.

His research accomplishments have been recognized with an A.P. Sloan Fellowship, Camille and Henry Dreyfus Teacher-Scholar Award, Guggenheim Fellowship, Presidential Young Investigator Award (USA), Polanyi Award, Rutherford Medal in Chemistry, the Chemical Institute of Canada (CIC) Medal, and numerous named lectureships.  He was inducted as a Fellow of the Royal Society of Canada, Fellow of the CIC, Fellow of the Optical Society of America, and distinguished University Professor at the University of Toronto.  He recently received the E. Bright Wilson Award in Spectroscopy, conferred by the American Chemical Society (2015) and the Centennary Prize from the Royal Society of  Chemistry (2016).  He will be inducted as a Fellow of the Royal Society of Chemistry in November 2016.    He is also a strong advocate for science promotion earning the McNeil Medal from the Royal Society of Canada (2011) for founding Science Rendezvous, which is the largest celebration of science (geographically at least) with over 300 events all across Canada with new initiatives in the North, aimed to make science accessible to the general public with over 200,000 attendees annually made possible by 5000 volunteers/researchers.

Tracing his career to this point, R. J. Dwayne Miller began his academic career at the University of Rochester direct from PhD (Stanford,1983), then moved to the University of Toronto (1995) where he still holds a partial appointment, then to the University of Hamburg (2010) and on January 1, 2014, he officially took up the position as co-Founding Director of the newly created Max Planck Institute for the Structure and Dynamics of Matter in Hamburg.  He also led the Excellent Research Initiative that led to the creation of the Hamburg Centre for Ultrafast Imaging and is the founding co-Director of the Canadian Institute for Advanced Research Program in the Molecular Architecture of Life.