Richard Mathies

Research Interests

Development of microfluidic technologies and bioanalysis methods that advance genome sequencing, polymorphism characterization, pathogen detection, forensics and health care diagnostics.   Our approach is to exploit miniaturization of chemical and bioanalysis along with high-sensitivity fluorescence detection to produce integrated microfabricated lab-on-a-chip microanalysis systems.  We are now going beyond the traditional lab-on-a-chip concept to the development of chemical and biochemical microprocessors that integrate all aspects of sample processing and analysis.

Research Summary

MICROFABRICATED CHEMICAL AND BIOCHEMICAL ANALYSIS SYSTEMS
We are developing new bioanalytical technologies that will advance genome sequencing, polymorphism characterization, forensics, health care diagnostics, and space exploration.  Our approach is to exploit miniaturization of chemical and biochemical analysis along with high-sensitivity fluorescence detection to produce integrated microfabricated lab-on-a-chip microanalysis systems. We have developed microphotolithographic methods for fabricating capillary array electrophoresis (CAE) systems on glass wafers for rapid and sensitive sample analysis (1).  Methods have been developed for fabricating CAE chips with from 96 to 384 capillaries that are capable of analyzing large numbers of samples in parallel (2, 3).  With these devices very small amounts of sample are needed, the electrophoretic separations are 10-100 times faster than conventional techniques, and miniaturization  permits the  fabrication  of  massively parallel  as well as miniaturized portable analysis  devices (4,5). We have also developed methods for integrating PCR-based sample preparation on these chips together with microfabricated valves, pumps and routers to make the first miniaturized DNA analysis bioprocessors (6, 7).  These technologies have been used to develop chips that integrate the entire process of Sanger DNA sequencing, chips that can measure single cell genetic variation and expression, chips for real-time forensic analysis, and chips for pathogen detection (8-11).  Finally, a significant effort is focused on the development and testing of microfabricated biomarker detection systems that will be used to explore our solar system for chemical signs of life.  In particular we have developed an instrument for amino acid detection and analysis called the Mars Organic Analyzer (12) that has been selected for the 2013 European ExoMars mission.

Selected Publications

1. Simpson, P. C., Woolley, A. T. and Mathies, R. A.. Biomedical Microdevices  1,  7-25 (1998).

2.  Paegel, B. M., Emrich, C. A., Wedemayer, G. J.,  Scherer, J. R. and Mathies, R. A., Proc. Natl. Acad. Sci. U.S.A., 99, 574-579 (2002).

3.  Emrich, C. A., Tian, H., Medintz, I. and Mathies, R. A. Anal. Chem., 74, 5076-5083 (2002).

4.  Paegel, B. M., Blazej, R. G., and Mathies, R. A.  Current Opinions in Biotechnology, 14, 42-50 (2003).

5. Lagally, E. T. and Mathies R. A.  Integrated Genetic Analysis Systems, J. Phys. D., 37, R245-R261 (2004).

6. Lagally, E. T., Emrich, C. A. and Mathies, R. A. Lab-on-A-Chip, 1 (2) 102-107 (2001).

7. Grover, W. H., Ivester, R. H. C., Jensen, E. C. and Mathies, R. A. Lab on a Chip 6, 623-631 (2006).

8.  Blazej, R. G., Kumaresan, P. and Mathies, R. A. Proc. Natl. Acad. Sci. U.S.A.  103, 7240-7245 (2006).

9. Toriello, N. M., Lui, C. N., Mathies, R. A., Anal. Chem., 78, 7997-8003 (2006).

10. Liu, P., Seo, T. S., Beyor, N., Shin, K., Scherer, J. R., and Mathies, R. A. Anal. Chem., 79, 1881-1889 (2007).

11.  Lagally, E. T., Scherer, J. R.,  Blazej, R. G., Toriello, N. M., Diep, B. A. , Ramchandani, M.,  Sensabaugh, G. F., Riley, L. W. and Mathies, R. A., Analytical Chemistry, 76, 3162-3170 (2004).

12.      Skelley, A. M., Scherer, J. R., Aubrey, A. D., Grover, W. H., Ivester, R. H. C., Ehrenfreund, P., Grunthaner, F. G., Bada, J. L. and Mathies, R. A. Proc. Natl. Acad. Sci. U.S.A., 102, 1041-1046 (2005).