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William Grover

Current position: Assistant Professor, UC Riverside

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Education

Ph.D. Chemistry, University of California, Berkeley, 2006

B.S. Chemistry, University of Tennessee, Knoxville, 1999

Research

Measurements of cell size provide fundamental insights into the mechanisms of cell growth. Coulter counters, flow cytometers, and most other tools for measuring cell size actually measure cell volume, which can be affected by the cellular environment and provides only part of the cell-size picture. Only by measuring cell mass along with cell volume (and their ratio, cell density) can a complete picture of cell size be obtained. In addition, most existing tools for measuring cell size measure each cell only once and cannot be used to monitor single-cell growth over time.

Our group’s Suspended Microchannel Resonator (SMR) has previously been used to measure the mass of single living cells. I am working to apply the SMR toward the simultaneous measurement of cell mass, volume, and density. As the cell passes through the resonating cantilever in the SMR, the resonance frequency of the cantilever changes in proportion to the buoyant mass of the cell. By quickly exchanging the buffer surrounding a cell between mass measurements, each cell can be weighed in buffers of two different densities. From these two mass measurements, the absolute mass, volume, and density of the cell can be calculated.

We have demonstrated two applications for this new technique. In the first application, a population of cells can be sized to construct a scatter plot of cell volume vs. mass. We are currently investigating whether this plot could be used to differentiate cell types that would otherwise be indistinguishable by volume or mass measurements alone. In the second application, single cells can be trapped in the SMR and continuously sized as the cell grows. This could provide not only information about how fast cells grow at each step in their cell cycles but also insight into the mechanism of that growth (incorporating new mass, increasing volume, or both).

Selected Publications

M. Godin, F.F. Delgado, S. Son, W.H. Grover, A.K. Bryan, A. Tzur, P. Jorgensen, K. Payer, A.D. Grossman, M.W. Kirschner, and S.R. Manalis, Using buoyant mass to measure the growth of single cells. Nature Methods 7, 387 – 390 (2010).

S. Son, W.H. Grover, T.P. Burg, and S.R. Manalis, Suspended microchannel resonators for ultra-low volume universal detection. Analytical Chemistry 80, 2008, 4757-5760.

W.H. Grover, M.G. von Muhlen, and S.R. Manalis, Teflon films for chemically-inert microfluidic valves and pumps. Lab on a Chip 8, 2008, 913-918.

W.H. Grover, Y.-C. Weng, and S.R. Manalis. A microfluidic autosampler with true Teflon valves: Design and application to suspended microchannel resonator mass sensors. Proceedings of the 11th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Paris, France, 2007.

B.M. Paegel, W.H. Grover, A.M. Skelley, R.A. Mathies, and G.F. Joyce. Microfluidic Serial Dilution Circuit. Analytical Chemistry 78, 2006.

A.M. Skelley, J.R. Scherer, A.D. Aubrey, W.H. Grover, R.H.C. Ivester, P. Ehrenfreund, F.J. Grunthaner, J.L. Bada, and R.A. Mathies. Development and Evaluation of a Microdevice for Amino Acid Biomarker Detection and Analysis on Mars. Proceedings of the National Academy of Sciences of the USA 102 (4), 2005.

W.H. Grover and R.A. Mathies. An Integrated Microfluidic Processor for Single Nucleotide Polymorphism-based DNA Computing. Lab on a Chip 5 (10), 2005.

W.H. Grover, A.M. Skelley, C.N. Liu, E.T. Lagally and R.A. Mathies. Monolithic Membrane Valves and Diaphragm Pumps for Practical Large-scale Integration into Glass Microfluidic Devices. Sensors and Actuators B 89 (3), 2003.

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