Richard A. Mathies

Richard Mathies

Professor of the Graduate School

email: ramathies@berkeley.edu
phone: 510 642-4192
office: 307 Lewis Hall
labs: 309, 311 and 313 Lewis Hall

Research Group Site
Publications
62,000 lifetime citations; h = 141


Research Accomplishments

Physical, Biophysical and Bioanalytical Chemistry — Prof. Mathies has developed a variety of modern laser-based spectroscopic techniques to study excited-state reaction dynamics in photoactive proteins and to develop novel microfabricated chemical and biochemical analysis devices for terrestrial and extra-terrestrial applications.

Ultrafast Vibrational Spectroscopy of Reaction Dynamics. Mathies has used resonance Raman vibrational spectroscopy to study photochemical reaction dynamics of energy and information transducing systems especially the primary photochemistry of rhodopsins. Most recently his group developed the novel technique of Femtosecond Stimulated Raman Spectroscopy or FSRS that enables the acquisition of femtosecond time-resolved vibrational structure snapshots of reacting molecules.

In particular, we have used the analysis of resonance Raman intensities, femtosecond time resolved absorption and FSRS to determine the molecular details of the primary photochemistry of the visual pigment rhodopsin. Our work showed that the primary photochemistry, the 11-cis to trans isomerization of the retinal chromophore bound in the protein opsin, completes its journey from reactant to strained trans photoproduct in only 200 femtoseconds. This is one of the fastest and most efficient photochemical reactions in nature and the trigger for all visual reception. The crucial role of coordinated hydrogen out-of-plane or HOOP wagging motions with skeletal torsional motion along the isomerization coordinate revealed the first vibrational phase isotope effect on chemical reaction dynamics.

Bioanalytical Chemistry and Genomic Analysis. In the bioanalytical research area, we exploit the sensitivity of laser-excited fluorescence detection to develop high-performance biochemical analysis methods and microfabricated lab-on-a-chip chemical and biochemical analysis devices. In our early work we developed the first capillary array electrophoretic sequencing devices for high throughput DNA sequencing. Together with our development of Energy Transfer fluorescent dye labels for Sanger sequencing, this technology enabled the sequencing of the first human genome - a landmark in advancing our understanding of the molecular basis of life.

We then turned our attention to the use of photolithography to produce a variety of microfabricated chemical and biochemical analysis systems. This work included the development of the first microfabricated capillary array analyzer, the first integrated PCR capillary electrophoresis system, and the first fully integrated PCR-CE device for forensic short tandem repeat analysis. The latter technology was commercially developed and is currently sold by Thermo-Fischer to law enforcement agencies for real-time forensic identification.

Microfabricated Analysis Systems for Planetary Exploration. Another area where integrated, compact low-mass analytical systems are critical is the exploration of our solar system for habitable environments and possible extraterrestrial life. Our approach is to search for chemical biosignatures such as amino acids and to use amino acid composition and chirality as a probe for possible biological origins. We first developed the Mars Organic Analyzer or MOA that labeled organic amines with an amine reactive fluorescent dye followed by capillary electrophoresis analysis in a microfabricated chip. This system demonstrated a target sensitivity of a few 10’s of femtomolar with rapid high-resolution analysis. We successfully tested this instrument in field trips to the Atacama Desert in Chile and other Mars analog sites. More recent work has focused on the integration of biosignature CE analysis with sample processing and preparation in a fully integrated low-mass flight format package. This instrument has been designed for a mission to the icy moons of Saturn and/or Jupiter (Enceladus and Europa) which might inform about the existence of extraterrestrial life.

Biography

  • Born, Seattle WA (1946)
  • B. S. Chemistry, University of Washington (1968)
  • Ph. D. Physical Chemistry, Cornell University (1973)
  • Helen Hay Whitney Postdoctoral Fellow, Yale University (1973-1976)
  • Alfred P. Sloan Research Fellow (1979-1981)
  • NIH Research Career Development Awardee (1981-1986)
  • Harold Lamport Award, New York Academy of Sciences (1983)
  • American Society for Photobiology Research Award (1989)
  • Frederick Conference on Capillary Electrophoresis Award (1998)
  • Association for Laboratory Automation Research Award (2001)
  • Ellis R. Lippincott Award from Optical Society of America (2004)
  • Fellow of Optical Society of America (2004)
  • Fellow of the Society for Applied Spectroscopy (2008)
  • G. N. Lewis Professor of Chemistry; Dean College of Chemistry (2008-2013)
  • ACS Analytical Division Award in Chemical Instrumentation (2010)
  • Emeritus Chemistry Professor in the Graduate School (2013-present)
  • Inducted to the National Academy of Inventors (2015)

Recent Publications (PDF)