Department of Chemistry

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Steve Weber

Professor

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603A CHVRN
Chevron Science Center, 219 Parkman Avenue

Pittsburgh, PA 15260
412-624-8520

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Research Overview

Bioanalytical Chemistry

The Weber group studies a variety of problems in analytical chemistry and related areas. We use a broad array of techniques in the pursuit of a quantitative understanding of the systems that we develop. Separations and electrochemistry are generally our focus, but we own or share with another group a variety of spectroscopic instrumentation, e.g. fluorescence, spr, FTIR, and triple quadruple mass spectrometry. Students and postdocs who have left in the last few years have full-time positions at Pfizer, Microbia, Mylan Labs, Schering Plough, Waters, Geneva College, Austin Peay State University, San Diego State University and Michigan Technological University, University of Wisconsin, Thomas Jefferson University.

We are developing molecularly selective microextractions using artificial receptors. This research promises to have a dramatic impact on analysis. Through the improved selectivity of extraction, fewer components of analytical systems will be introduced into separation/detection systems leading to better detection limits and higher speed analysis. This work is also green chemistry, as we use nonvolatile polymeric systems as the organic solvents for two-phase extractions from aqueous solution. These thin films are used in a procedure called Solid-Phase MicroExtraction or SPME. A former student, Shu Li, was the first to couple SPME to CE. Current work focuses on selective extraction of barbiturates followed by capillary electrophoretic (CE) separation of the drugs.

We are also developing novel and powerful separations based on molecular recognition, such as the interaction with lanthanides and oxygen-containing organic molecules. This has been used to separate neutral organic molecules in nonaqueous solvents by capillary electrophoresis.

In a new project just getting underway, we are collaborating with Professor Peter Wipf of this Department to develop chiral stationary phases using combinatorial chemistry.

Peptides have many important control functions in the body. The usual methods for their determination are simple, accurate and precise, but in order to apply these methods you have to know what you are looking for in order to determine it. What do you do if you want to hunt for new molecules that influence how we think, feel, and act? We are vigorously developing a chromatographic approach which is sensitive and selective. Even now, as the technique is under development, we are making advances that will have an impact in neurochemistry. We are basing the determination on the combination of liquid chromatography and electrochemical detection of copper complexes of peptides. The copper complexes of peptides that are three amino acids or longer are oxidizable (Cu(II)to Cu(III)), and it is this electrochemistry that we use for the detection. One current application we are pursuing is the hunt for acidic dipeptides in the brain. An unbelievably small amount of information is available on the distribution and concentrations of dipeptides in the brain, where as volumes have been written on the amino acids. Recent discoveries that we have made allow the determination of dipeptides at subpicomole levels.

In addition to separation and detection, we are working on sampling protocols. In one project, a collaboration with Professors Michael and Grabowski, we are using small tubes to pull minute quantities of fluid from brain. In another project with Prof. Owe Orwar at Chalmers in Sweden, we are trying to understand how to sample the contents of single, living cells.

The need to work with very small sample volumes requires making small separation and detection systems. We have recently developed novel construction techniques that allow us to mix reagents with chromatographic effluent without significant band spreading.

Our expertise in moving fluids in small volumes has led to research directed towards the discovery of new catalysts to organic reactions. This work, carried out with Professor Scott Nelson of this Department is just getting underway.

Awards

  • Dal Nogare Award of the Chromatography Forum of the Delaware Valley 2016
  • Palmer Award, Minnesota Chromatography Forum 2015; The Provost's Award for Excellence in Mentoring, 2012
  • The Pittsburgh Award, Pittsburgh Section, American Chemical Society, 2008
  • Visiting Scientist Fellow of the Swedish Medical Research Council, 1991-92

Publications

“Quantitative evaluation of models for solvent-based, on-column focusing in liquid chromatography,” Groskreutz, S. R.; Weber, S. G., J. Chromatogr. A accepted, 2015,
“In vivo Monitoring of Dopamine by Microdialysis with One-Minute Temporal Resolution Using Online Capillary Liquid Chromatography with Electrochemical Detection,” Gu, H.; Varner, E.; Groskreutz, S.; Michael, A.; Weber, S. G., Anal. Chem. accepted., 2015,
“Fluorous receptor-facilitated solid phase microextraction,” Lu, Dujuan; Weber, Stephen G., Journal of Chromatography A, Vol. 1360, 2014, Pages 17-22
“Electroosmotic perfusion of tissue: sampling the extracellular space and quantitative assessment of membrane-bound enzyme activity in organotypic hippocampal slice cultures,” Ou, Yangguang; Wu, Juanfang; Sandberg, Mats; Weber, Stephen G., Analytical and Bioanalytical Chemistry, Vol. 406, 2014, Pages 6455-6468
“Temperature-assisted On-column Solute Focusing: A General Method to Reduced Pre-column Dispersion in Capillary High Performance Liquid Chromatography,” Groskreutz, S. R.; Weber, S. G., J. Chromatogr. A, Vol. 1354, 2014, Pages 65-74
“NRF2-Regulation in Brain Health and Disease: Implication of Cerebral Inflammation,” Sandberg, M.; Patil, J.; D’Angelo, B.; Weber, S. G.; Mallard, C., Neuropharmacology, Vol. 79, 2014, Pages 298-307
“Assessment of tissue viability following electroosmotic push-pull perfusion from organotypic hippocampal slice cultures,” Rupert, A. E.; Ou, Y.; Sandberg, M.; Weber, S. G., ACS Chemical Neuroscience, Vol. 4, 2013, Pages 849-857
“Morphology and free volume of nanocomposite Teflon AF 2400 films and their relationship to transport behavior,” Zhang, H.; Wang, S.; Weber, S.G., J. Membrane Sci., Vol. 443, 2013, Pages 115-123
“Nanocomposite Teflon AF 2400 Films as Tunable Platforms for Selective Transport,” Zhang, Hong; Wang, Sijia; Weber, Stephen G., Anal. Chem., Vol. 84, 2012, Pages 9920-27
“Lipophilicity Screening of Novel Drug-Like Compounds and Comparison to cLog P,” Lu, D.; Chambers, P.; Wipf, P.; Xie, X.-Q.; Englert, D.; Weber, S., J. Chromatogr. A, Vol. 1258, 2012, Pages 161-167
“Optimization for speed and sensitivity in capillary high performance liquid chromatography. The importance of column diameter in online monitoring of serotonin by microdialysis.,” Zhang, J.; Liu, Y.; Jaquins-Gerstl, A.; Shu, Z.; Michael, A.C.; Weber, S. G., J. Chromatogr. A, Vol. 1251, 2012, Pages 54-62
“Iontophoresis from a micropipet into a porous medium depends on the ζ-potential of the medium,” Guy, Y.; Faraji, A. H.; Gavigan, C. A.; Strein, T. G.; Weber, S. G., Anal. Chem., Vol. 84, 2012, Pages 2179–2187
“The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK,” Correa Fernando; Ljunggren Elin; Mallard Carina; Nilsson Michael; Weber Stephen G; Sandberg Mats, Glia, Vol. 59, 2011, Pages 785-99
“Synthesis and Characterization of a Hydrogel with Controllable Electroosmosis: A Potential Brain Tissue Surrogate for Electrokinetic Transport,” Faraji, Amir H.; Cui, Jonathan J.; Guy, Yifat; Li, Ling; Weber, Stephen G., Langmuir, accepted, 2011,
“The effect of dexamethasone on gliosis,ischemia, and dopamine extraction during mircrodialysis sampling in brain tissue,” Jaquins-Gerstl, A.; Shu, Z.; Zhang, J.; Liu, Y.; Weber, S. G.; Michael, A., Anal. Chem., Vol. 83, 2011, Pages 7662-7667
“Teflon AF materials,” Zhang, H.; Weber, S. G., Topics in Current Chemistry, Vol. 308, 2011, Pages 307-337
“A simple method for measuring organotypic tissue slice culture thickness,” Guy Yifat; Rupert Amy E; Sandberg Mats; Weber Stephen G, J. Neurosci. Meth., Vol. 199, 2011, Pages 78-81
“Luminescence targeting and imaging using a nanoscale generation 3 dendrimer in an in vivo colorectal metastatic rat model,” Alcala, Marco; Uh, Hyounsoo; Shade, Chad; Bartlett, David; Weber, Stephen G; Petoud, Stephane; Lee, Yong, Nanomedicine, Vol. 7, 2011, Pages 249-258
“Properties and Transport Behavior of Perfluorotripentylamine (FC-70)-Doped Amorphous Teflon AF 2400 Films,” Zhang, Hong; Hussam, Abul; Weber, Stephen G., J. Am. Chem. Soc., Vol. 132, 2010, Pages 17867-17879
“Electroosmotic sampling. application to determination of ectopeptidase activity in organotypic hippocampal slice cultures,” Xu, H.; Guy, Y.; Hamsher, A.; Shi, G.; Sandberg, M.; Weber, S. G., Anal. Chem., Vol. 82, 2010, Pages 6377-6383
“Integration of a precolumn fluorogenic reaction, separation, and detection of reduced glutathione,” Wu, J.; Ferrance, J. P.; Landers, J. P.; Weber, S. G., Anal. Chem., Vol. 82, 2010, Pages 7267-7273
“Single-cell electroporation,” Wang, Manyan; Orwar, Owe; Olofsson, Jessica; Weber, Stephen G., Anal. Bioanal. Chem., Vol. 397, 2010, Pages 3235-3248
“A functionalizable polyester with free hydroxyl groups and tunable physiochemical and biological properties,” You ZW, Cao HP, Gao J, et al., Biomaterials, Vol. 31, 2010, Pages 3129-3138
“Fluorous Receptor-Facilitated Solid Phase Microextraction,” Lu, D.; Weber, S.G., J. Chromatogr. A, Vol. 1360, 2014, Pages 17-22