Ph.D. in Biophysics, University of California at Berkeley, December 2007
B.S. in Biochemistry and B.S. in Math, University of Texas, June 2001
I’m interested in applying high-throughput imaging systems to learn new things about biological systems and develop new technologies. Whether tracking millions of microspheres in 3D as they interact with a surface or tracking multiple mouse whiskers through thousands of images, the statistical power of these studies can yield unique insights. The careful consideration of rare events is a requirement for these studies and provides opportunities for interesting hardware and software development. Currently, I’m working on developing a platform for high-throughput detailed neuroanatomy in the mouse brain.
DNA microarrays are used for gene-expression profiling, single-nucleotide polymorphism detection and disease diagnosis. A persistent challenge in this area is the lack of microarray screening technology suitable for integration into routine clinical care. Here, we describe a method for sensitive and label-free electrostatic readout of DNA or RNA hybridization on microarrays. The electrostatic properties of the microarray are measured from the position and motion of charged microspheres randomly dispersed over the surface. We demonstrate nondestructive electrostatic imaging with 10-mum lateral resolution over centimeter-length scales, which is four-orders of magnitude larger than that achievable with conventional scanning electrostatic force microscopy. Changes in surface charge density as a result of specific hybridization can be detected and quantified with 50-pM sensitivity, single base-pair mismatch selectivity and in the presence of complex background. Because the naked eye is sufficient to read out hybridization, this approach may facilitate broad application of multiplexed assays.
We have developed and characterized a method, based on reflection interference contrast microscopy, to simultaneously determine the three-dimensional positions of multiple particles in a colloidal monolayer. To evaluate this method, the interaction of 6.8 microm (+/-5%) diameter lipid-derivatized silica microspheres with an underlying planar borosilicate substrate is studied. Measured colloidal height distributions are consistent with expectations for an electrostatically levitated colloidal monolayer. The precision of the method is analyzed using experimental techniques in addition to computational bootstrapping algorithms. In its present implementation, this technique achieves 16 nm lateral and 1 nm vertical precision.