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

NO-Releasing Antibacterial Agents

Researchers in the Schoenfisch Group, have published research in Acta Biomaterialia, where they describe how S-Nitrosothiol-modified chitosan oligosaccharides were synthesized by reaction with 2-iminothiolane hydrochloride and 3-acetamido-4,4-dimethylthietan-2-one, followed by thiol nitrosation. The resulting nitric oxide (NO)-releasing chitosan oligosaccharides stored approximately 0.3 micromol NO mg-1 chitosan. Both the chemical structure of the nitrosothiol, that is primary and tertiary, and the use of ascorbic acid as a trigger for NO donor decomposition were used to control the NO-release kinetics. With ascorbic acid, the S-nitrosothiol-modified chitosan oligosaccharides elicited a 4-log reduction in Pseudomonas aeruginosa viability.

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Confocal microscopy indicated that the primary S-nitrosothiol-modified chitosan oligosaccharides associated more with the bacteria relative to the tertiary S-nitrosothiol system. The primary S-nitrosothiol-modified chitosan oligosaccharides elicited minimal toxicity towards L929 mouse fibroblast cells at the concentration necessary for a 4-log reduction in bacterial viability, further demonstrating the potential of S-nitrosothiol-modified chitosan oligosaccharides as NO-release therapeutics.

Microfluidic Mass Spec Detection

Biotherapeutics, monoclonal antibodies, mAbs, in particular, represent a multi-billion dollar industry that continues to expand. In order to be used as a therapeutic agent the biomolecule must be rigorously characterized in order to ensure safety, efficacy, and potency. However, the size and complexity of mAbs makes this a challenging task. In work published in Analytical Chemistry, researchers in the Ramsey Group describe an integrated microfluidic capillary electrophoresis-electrospray ionization, CE-ESI, device for the separation of intact monoclonal antibody charge variants with online mass spectrometric, MS, identification.

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Schematic for CE-ESI devices with a 23 cm separation channel with an enlarged image of the asymmetric turn tapering. Red channels indicate an APS coating while black channels indicate an APS-PEG450 coating. S: sample reservoir; B: background electrolyte reservoir; SW: sample waste reservoir; EO: electroosmotic pump reservoir.

The surface chemistry utilized in the device channels suppressed the electroosmotic flow and prevented analyte adsorption, eliminating the need for complex background electrolyte additives. The microfluidic ESI interface proved vital to the successful ionization and resulting MS analysis by maintaining fluid flow to generate stable ESI. The effectiveness of the technique was demonstrated with the determination of five charge variants in the separation of Infliximab with an additional two mAbs analyzed to show the general applicability of the approach.

 

Representative Publications

Low-Temperature Plasma Ionization-Mass Spectrometry for the Analysis of Compounds in Organic Aerosol Particles. Sandra E. Spencer , Chelsea A. Tyler , Michael P. Tolocka , and Gary L. Glish. Anal. Chem., 2015, 87 (4), pp 2249–2254.

S-Nitrosothiol-Modified Nitric Oxide-Releasing Chitosan Oligosaccharides as Antibacterial Agents. Yuan Lu, Anand Shah, Rebecca A. Hunter, Robert J. Soto, Mark H. Schoenfisch. Acta Biomaterialia, Volume 12, 15 January 2015, Pages 62–69.

Integrated Microfluidic Capillary Electrophoresis-Electrospray Ionization Devices with Online MS Detection for the Separation and Characterization of Intact Monoclonal Antibody Variants. Erin A. Redman, Nicholas G. Batz, J. Scott Mellors, and J. Michael Ramsey. Anal. Chem., 2015, 87 (4), pp 2264–2272.

High Process Yield Rates of Thermoplastic Nanofluidic Devices Using a Hybrid Thermal Assembly Technique. Franklin I. Uba, Bo Hu, Kumuditha Weerakoon-Ratnayake, Nyote Oliver-Calixte, and Steven A. Soper. Lab Chip, 2015, Advance Article, DOI: 10.1039/C4LC01254B.

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.