Richard A. Mathies

Physical, Biophysical and Bioanalytical Chemistry — Prof. Mathies has developed laser-based spectroscopic techniques to study excited-state reaction dynamics in photoactive proteins as well as 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 the primary visual photochemistry of rhodopsins. Most recently his group developed the technique of Femtosecond Stimulated Raman Spectroscopy or FSRS that enables the acquisition of femtosecond time-resolved vibrational structure snapshots of reacting molecules.

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 important role of vibrational coherence in the chemical reaction dynamics.

Bioanalytical Chemistry and Genomic Analysis. The sensitivity of laser-excited confocal fluorescence detection enables the development of high-performance biochemical analysis methods and microfabricated lab-on-a-chip analysis devices. We developed the first capillary array electrophoretic sequencing instruments for high throughput DNA sequencing. Together with our development of Energy Transfer fluorescent dye labels for Sanger sequencing, this technology facilitated the first sequencing of the human genome.

We then turned our attention to the use of photolithography to produce 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 sold by Thermo-Fischer to law enforcement agencies for real-time forensic identification.

Microfabricated Analysis Systems for Planetary Exploration. We have also exploited our integrated, low-mass microdevices for the development of instruments to explore 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 that labeled organic amines with an amine reactive fluorescent dye followed by capillary electrophoresis analysis in a microfabricated chip. This instrument was successfully tested 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 that was recently tested in ZeroG parabolic flights. This instrument has been designed for a mission to the icy moons of Saturn and/or Jupiter (Enceladus and Europa) which are likely sites for extraterrestrial life within our solar system.

Golozar, M., Chu, W.K., Casto, L.D., McCauley, J., Butterworth, A., Mathies, R.A. (2020) Fabrication of High-Quality Glass Microfluidic Devices for Bioanalytical and Space Flight Applications, MethodsX, 7 101043, doi.org/10.1016/j.mex.2020.101043.

Casto-Boggess, L. D., Golozar, M., Butterworth, A. L. and Mathies, R. A. (2021) Optimization of Fluorescence Labeling of Trace Analytes: Application to Amino Acid Biosignature Detection with Pacific Blue, Anal. Chem. 94, 1240-1247.

Butterworth, AL, Golozar, M, Estlack, Z, McCauley, J, Mathies, RA, and Kim J. (2024) Integrated high performance microfluidic organic analysis instrument for planetary and space exploration. Lab on a Chip 24 (9)2551-2560.