Department of Chemistry

Analytical Chemistry

Research ImageConsistently ranked as one of the top analytical divisions in the United States, ranked number 1 for the fifth year in a row by U.S. News and World Report magazine in its 2011 edition of "America's Best Graduate Schools," the analytical division is recognized as a world leader in this scientific area.

Following the tradition set by the late Professor Charles N. Reilley, the division extends the frontier of the field through a focus on fundamental studies related to chemical analysis and the development of innovative instrumentation. All traditional areas of research are represented, including electrochemistry, mass spectrometry, microscopy, sensors, separations and spectroscopy.

Research projects span a wide range of chemical analysis science and include, but are not limited to, biosensors, nanoscopic materials, neurochemistry, microvolume separations and analysis, protein adsorption, supercritical fluids and single-molecule analysis; for examples of currently active research projects please see the list below. The division has strong relationships with a large number of companies in the pharmaceutical, chemical and scientific instrumentation industries, which provide continued support of research fellowships and the Analytical Seminar series.

 

Recent Research Highlights

Cerebral Blood Flow

Neurovascular coupling is understood to be the underlying mechanism of functional hyperemia, but the actions of the neurotransmitters involved are not well characterized. In an article published in the Journal of Cerebral Blood Flow & Metabolism, researchers in the Wightman Group investigate the local role of the neurotransmitter norepinephrine in the ventral bed nucleus of the stria terminalis, vBNST, of an anesthetized rat by measuring O2, which is delivered during functional hyperemia. Extracellular changes in norepinephrine and O2 were simultaneously monitored using fast-scan cyclic voltammetry. Introduction of norepinephrine by electrical stimulation of the ventral noradrenergic bundle or by iontophoretic ejection induced an initial increase in O2 levels followed by a brief dip below baseline.

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Supporting the role of a hyperemic response, the O2 increases were absent in a brain slice containing the vBNST. Administration of selective pharmacological agents demonstrated that both phases of this response involve β-adrenoceptor activation, where the delayed decrease in O2 is sensitive to both α- and β-receptor subtypes. Selective lesioning of the locus coeruleus with the neurotoxin DSP-4 confirmed that these responses are caused by the noradrenergic cells originating in the nucleus of the solitary tract and A1 cell groups. Overall, these results support that non-coerulean norepinephrine release can mediate activity-induced O2 influx in a deep brain region.

 

Massively Parallel Clonogenic Screening

Wnt/β-catenin signaling is of significant interest due to the roles it plays in regulating development, tissue regeneration and disease. Transcriptional reporters have been widely employed to study Wnt/β-catenin signal transduction in live cells and whole organisms and have been applied to understanding embryonic development, exploring oncogenesis and developing therapeutics. Polyclonal heterogeneity in reporter cell lines has historically been seen as a challenge to be overcome in the development of novel cell lines and reporter-based assays, and monoclonal reporter cell lines are commonly employed to reduce this variability.

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Published in Integrative Biology, researchers in the Allbritton Group describe how A375 cell lines infected with a reporter for Wnt/β-catenin signaling were screened over short (<6) and long (>25) generational timescales. To characterize phenotypic divergence over these time-scales, a microfabricated cell array-based screen was developed enabling characterization of 1119 clonal colonies in parallel. This screen revealed phenotypic divergence after <6 generations at a similar scale to that observed in monoclonal cell lines cultured for >25 generations. Not only were reporter dynamics observed to diverge widely, but monoclonal cell lines were observed with seemingly opposite signaling phenotypes. Additionally, these observations revealed a generational-dependent trend in Wnt signaling in A375 cells that provides insight into the pathway's mechanisms of positive feedback and self-inhibition.

 

Representative Publications

In Vivo Analytical Performance of Nitric Oxide-Releasing Glucose Biosensors. Robert J. Soto, Benjamin J. Privett, and Mark H. Schoenfisch. Anal. Chem., 2014, 86 (14), pp 7141–7149.

Medullary Norepinephrine Neurons Modulate Local Oxygen Concentrations in the Bed Nucleus of the Stria Terminalis. Elizabeth S Bucher, Megan E Fox, Laura Kim, Douglas C Kirkpatrick, Nathan T Rodeberg, Anna M Belle and Mark Wightman. Journal of Cerebral Blood Flow & Metabolism (2014) 34, 1128–1137.

Dynamics and Evolution of β-Catenin-Dependent Wnt Signaling Revealed through Massively Parallel Clonogenic Screening. Pavak K. Shah, Matthew P. Walker, Christopher E. Sims, Michael B. Major, and Nancy L. Allbritton. Integr. Biol., 2014,6, 673-684.

Small Sample Sorting of Primary Adherent Cells by Automated Micropallet Imaging and Release. Pavak K. Shah, Silvia Gabriela Herrera-Loeza, Christopher E. Sims, Jen Jen Yeh, and Nancy L. Allbritton. Cytometry Part A, Volume 85, Issue 7, pages 642–649, July 2014.

Optimization of 3-D Organotypic Primary Colonic Cultures for Organ-on-Chip Applications. Asad A Ahmad, Yuli Wang, Adam D Gracz, Christopher E Sims, Scott T Magness and Nancy L Allbritton. Journal of Biological Engineering 2014, 8:9.

Immobilization of Lambda Exonuclease onto Polymer Micropillar Arrays for the Solid-Phase Digestion of dsDNAs. Nyoté J. Oliver-Calixte, Franklin I. Uba, Katrina N. Battle, Kumuditha M. Weerakoon-Ratnayake, and Steven A. Soper. Anal. Chem., 2014, 86 (9), pp 4447–4454.

Chemical Vapor Deposition of Aminopropyl Silanes in Microfluidic Channels for Highly Efficient Microchip Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry. Nicholas G. Batz, J. Scott Mellors, Jean Pierre Alarie, and J. Michael Ramsey. Anal. Chem., 2014, 86 (7), pp 3493–3500.

Micropallet Arrays for the Capture, Isolation and Culture of Circulating Tumor Cells from Whole Blood of Mice Engrafted with Primary Human Pancreatic Adenocarcinoma. Guohua Xu, Yansheng Ye, Xiaoli Liu, Shufen Cao, Qiong Wu, Kai Cheng, Maili Liu, Gary J. Pielak, and Conggang Li. Biosensors and Bioelectronics, Volume 54, 15 April 2014, Pages 476–483.

Fluorous Enzymatic Synthesis of Phosphatidylinositides. Weigang Huang, Angela Proctor, Christopher E. Sims, Nancy L. Allbritton, and Qisheng Zhang. Chem. Commun., 2014,50, 2928-2931.

Response of Single Leukemic Cells to Peptidase Inhibitor Therapy Across Time and Dose Using a Microfluidic Device. Michelle L. Kovarik, Alexandra J. Dickinson, Pourab Roy, Ranjit A. Poonnen, Jason P. Fine and Nancy L. Allbritton. Integr. Biol., 2014, 6, 164-174.