My research is focused on the application of the principles of fluid mechanics and mass transport to study transport in single cells using both established and emerging microscopy techniques. Current work focuses on the use of quantitative phase microscopy (QPM) to quantify mass distributions within single cells and multicellular clumps. The resulting measurements can be used to assess the total mass of, or the transport of mass within, individual cells.
Ongoing work focuses on:
1. Development of microfluidic systems to isolate lymphocytes based on functional properties.
The identification of T cell receptors (TCRs) against unknown antigens is a major bottleneck in the development of cancer immune therapies for a variety of reasons, including the low frequency of TCRs directed against self-antigens, the low affinity of these TCRs, and the small amount of tissue available per patient. Existing approaches to measure T cell response rely on bulk or surrogate assays, which do not directly measure T cell mediated cytotoxicity and are not suitable for the isolation of these rare cells. QPM provides a novel approach for the identification of these rare cells. This project will develop QPM to characterize and isolate T lymphocytes targeting cancers for which there is a clinical need and no known TCR.
2. Use of quantitative phase microscopy to study intracellular transport and quantify
cellular biophysical properties.
Cancer is intimately linked with disturbed signaling and mass transfer; however, most research into physical transport mechanisms in cancer has been at the multicellular level. This project will use QPM to provide insight into mass transport at the subcellular level by directly quantifying the changing distribution of mass within single cells over time.
3. Collaboration with colleagues in the David Geffen School of Medicine on applications ranging from stem cell biology to cancer therapeutics to sickle cell disease.
- Zangle, T.A., and M. A. Teitell, “Live cell mass profiling: An emerging approach in quantitative biophysics,”Nature Methods 2014, 11. 1221-1228.
- Zangle, T.A., M. A. Teitell and J. Reed, “Live cell interferometry quantifies dynamics of biomass partitioning during cytokinesis,” PLOS ONE 2014, 9. e115726.
- Zangle, T.A., J. Chun, J. Zhang, J. Reed, and M.A. Teitell, “Quantification of biomass and cell motion in human pluripotent stem cell colonies,” Biophysical Journal 2013, 105. 593-601.
- Zangle, T.A., D. Burnes, C. Mathis, O.N. Witte, and M.A. Teitell, “Quantifying biomass changes of single CD8+ T cells during antigen specific cytotoxicity,” PLOS ONE 2013, 8. e68916.
- Chun, J., T.A. Zangle, T.A. Kolarova, R.S. Finn, M.A. Teitell, and J. Reed, “Rapidly quantifying drug sensitivity of dispersed and clumped breast cancer cells by mass profiling,” Analyst 2012, 137. 5495-5498.
- Reed, J., J. Chun, T.A. Zangle, S. Kalim, J.S. Hong, S.E. Pefley, X. Zheng, J.K. Gimzewski and M.A. Teitell, “Rapid, massively parallel single-cell drug response measurements via live cell interferometry,” Biophysical Journal 2011, 101. 1025-1031.
- Suss, M.E., A. Mani, T.A. Zangle and J.G. Santiago, “Electroosmotic pump performance is affected by concentration polarizations of both electrodes and pump,” Sensors and Actuators A: Physical 2011, 165. 310-315.
- Zangle, T.A., A. Mani and J.G. Santiago, “Effects of constant voltage on time evolution of propagating concentration polarization,” Analytical Chemistry 2010, 82. 3114-3117.
- Zangle, T.A., A. Mani and J.G. Santiago, “Theory and experiments of concentration polarization and ion focusing at microchannel and nanochannel interfaces,” Chemical Society Reviews 2010, 39. 1014-1035.
- Strickland, D.G., M.E. Suss, T.A. Zangle and J.G. Santiago, “Evidence shows concentration polarization and its propagation can be key factors determining electroosmotic pump performance,” Sensors and Actuators B 2010, 143. 795-798.
- Zangle, T.A., A. Mani and J.G. Santiago, “On the propagation of concentration polarization from microchannel-nanochannel interfaces. Part II. Numerical and experimental study,” Langmuir 2009, 25. 3909-3916.
- Mani, A., T.A. Zangle and J.G. Santiago, “On the propagation of concentration polarization from microchannel-nanochannel interfaces. Part I. Analytical model and characteristic analysis,” Langmuir 2009, 25. 3898-3908.