26. February 2019

R. J. Dwayne Miller

Picosecond Infrared Laser (PIRL) Scalpel: Achieving Fundamental (Single Cell) Limits to Minimally Invasive Surgery and Biodiagnostics

Max Planck Institute for the Structure and Dynamics of Matter / Hamburg, Germany

The first atomic view of strongly driven phase transitions (Siwick et al, Science 2003) illustrated the mechanism to control nucleation growth to nm scales (nucleation as small as 10 molecules), which eliminates cavitation and associated highly damaging shock waves. 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. The pulses must be shorter than the time for nucleation growth but longer than peak power limitations to dielectric breakdown. The pulses are deliberately made to be in the picosecond domain to avoid peak power conditions leading to multiphoton ionization and potential long term health risk issues related to all ionizing radiation effects. This feature distinguishes this approach from femtosecond laser applications. The laser ablation process is driven within resonant 1-photon transitions in which the strong localization of the laser energy is provided by the extremely strong absorption of water in the 3 micron range. The strong absorption of water provides intrinsic confinement of the ablation process to the micron dimensions of a single cell in the longitudinal direction with lateral confinement defined by the laser focus conditions. The most common conventional lasers in clinical use involve either massive tissue damage due to shock wave and thermal transport resulting in burning and tissue necrosis or are highly ionizing. The Picosecond InfraRed (PIRL) scalpel readily cuts all tissues types and most importantly, the damage to surrounding tissue is negligible, with no discernable scar tissue formation – and stronger tensile strength than scar tissue. Damage is confined to a single cell border. In this respect, the long held promise of the laser for achieving the fundamental (single cell) limit to minimally invasive surgery has now been realized. However, this statement needs to be further qualified. If the wrong tissue or excessive tissue is removed, it hardly counts as minimally invasive even if done with single cell precision. It was also discovered that the PIRL interaction ejects entire proteins, even protein complexes into the gas phase intact. This observation has been rationalized on the basis that the entire process of vibrational excitation and coupling of water in the tissue to translational motion driving ablation occurs faster than collisional exchange of the excited water with the constituent proteins and the ensuing ablation occurs on time scales much faster than thermal fragmentation of the protein signatures. 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 spectrometry in which very detailed molecular fingerprints of different tissue types can be retrieved, as a “frozen snapshot” of the proteome, with cancer margins delineated. On the fly, molecular level pathology during surgery is now well within reach. Surgeons will soon have hundreds of molecular markers to guide their surgery to take surgery to a new level.

Equally important, by exploiting the technology developed for ultrabright electron sources for lighting up atomic motions, it is possible in principle to push mass spectrometry by several orders of magnitude to true single molecule detection limits for the earliest possible disease detection. The MS concept alone may provide the enabling technology to map the Human Proteoform (protein make up including post translationally modified proteins) as a road map to good health and ultimate guidance for surgical intervention. Could we push the limits to “Make a Molecular Map of the Cell”? The basic concepts for the laser ablation process, as well as applications for mass spectrometry as feedback in laser surgery, and towards fundamental limits in spatial mapping and biodiagnostics will be discussed – with the ultimate aim to map the cell.

Short Bio:
R. J. Dwayne Miller has published over 300 research articles, one book, and several reviews. He made seminal contributions to the development of coherent multidimensional spectroscopy methods and associated ultrafast laser technology, and most notably pioneered the development of 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. It is forming the basis for a new conceptual model for chemistry based on key reaction modes that unifies structure and dynamics to guide chemical intuition. As a testimony to the importance of basic research, the very first atomic movie provided new insight into strongly driven phase transitions involved in laser ablation that led to the ultimate limit in minimally invasive laser surgery with intact molecular signatures for guidance, and scar free healing.

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 received the E. Bright Wilson Award in Spectroscopy, conferred by the American Chemical Society (2015), the Centenary Prize from the Royal Society of Chemistry (2016), and Doctorate of Science Degree (honoris causa) from the University of Waterloo (2017). He recently received (Sept 2018) the European Physical Award for Laser Science for “Achieving the Fundamental Limit to Min. Invasive Surgery with Biodiagnostics” recognizing an important advance in medical applications. 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 350 events all across Canada with new initiatives for remote communities in the North, aimed to make science accessible to the general public with over 250,000 attendees annually, made possible by >6000 volunteers/researchers.