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

Response of Single Leukemic Cells

Single-cell methodologies are revealing cellular heterogeneity in numerous biological processes and pathologies. For example, cancer cells are characterized by substantial heterogeneity in basal signaling and in response to perturbations, such as drug treatment. In an article published in Integrative Biology, members of the Allbritton Group examined the response of 678 individual human acute myeloid leukemia cells to an aminopeptidase-inhibiting chemotherapeutic drug, Tosedostat, over the course of 95 days. Using a fluorescent reporter peptide and a microfluidic device, they quantified the rate of reporter degradation as a function of dose. While the single-cell measurements reflected ensemble results, they added a layer of detail by revealing unique degradation patterns and outliers within the larger population.

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Regression modeling of the data allowed us to quantitatively explore the relationships between reporter loading, incubation time, and drug dose on peptidase activity in individual cells. Incubation time was negatively correlated with the number of peptide fragment peaks observed, while peak area, which was proportional to reporter loading, was positively correlated with both the number of fragment peaks observed and the degradation rate. Notably, a statistically significant change in the number of peaks observed was identified as dose increased from 2 to 4 μM. Similarly, a significant difference in degradation rate as a function of reporter loading was observed for doses ≥2 μM compared to the 1 μM dose. These results suggest that additional enzymes may become inhibited at doses >1 μM and >2 μM, demonstrating the utility of single-cell data to yield novel biological hypotheses.

 

Ex Vivo Quantification of PTP

Published in Analytical Chemistry, scientists in the Allbritton Group in collaboration with colleagues from Pharmacology, Biostatistics and Endodontics, and Biomedical Engineering, all at UNC, and the National Health and Environmental Effects Research Laboratory, describe a novel method for the measurement of protein tyrosine phosphatase, PTP, activity in single human airway epithelial cells, hAECs, using capillary electrophoresis.

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Their technique involved the microinjection of a fluorescent phosphopeptide that is hydrolyzed specifically by PTPs. Initial results were then extended to a more physiologically relevant model system: primary hAECs cultured from bronchial brushings of living human subjects. The results demonstrate the utility and applicability of this technique for the ex vivo quantification of PTP activity in small, heterogeneous, human cells and tissues.

 

Representative Publications

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.

Ex Vivo Chemical Cytometric Analysis of Protein Tyrosine Phosphatase Activity in Single Human Airway Epithelial Cells. Ryan M. Phillips, Lisa A. Dailey, Eric Bair, James M. Samet, and Nancy L. Allbritton. Anal. Chem., 2014, 86 (2), pp 1291–1297.

Capture and 3D Culture of Colonic Crypts and Colonoids in a Microarray Platform. Yuli Wang, Asad A. Ahmad, Pavak K. Shah, Christopher E. Sims, Scott T. Magness and Nancy L. Allbritton. Lab Chip , 2013, 13, 4625-4634.

Flexible Software Platform for Fast-Scan Cyclic Voltammetry Data Acquisition and Analysis. Elizabeth S. Bucher, Kenneth Brooks, Matthew D. Verber, Richard B. Keithley, Catarina Owesson-White, Susan Carroll, Pavel Takmakov, Collin J. McKinney, and R. Mark Wightman. Anal. Chem., 2013, 85 (21), pp 10344–10353.

Nitric Oxide-Releasing Chitosan Oligosaccharides as Antibacterial Agents. Yuan Lu, Danielle L. Slomberg, and Mark H. Schoenfisch. Biomaterials; online, 20 November, 2013.

Role of Size and Shape on Biofilm Eradication for Nitric Oxide-Releasing Silica Nanoparticles. Danielle L. Slomberg, Yuan Lu, Angela D. Broadnax, Rebecca A. Hunter, Alexis W. Carpenter, and Mark H. Schoenfisch. ACS Appl. Mater. Interfaces, 2013, 5 (19), pp 9322–9329.

Scalable Synthesis of a Biocompatible, Transparent and Superparamagnetic Photoresist for Microdevice Fabrication. P K Shah, M R Hughes, Y Wang, C E Sims and N L Allbritton. J. Micromech. Microeng. 23 107002, P K Shah et al 2013.

Polaronic Transport and Current Blockades in Epitaxial Silicide Nanowires and Nanowire Arrays. Violeta Iancu, X.G. Zhang, Tae-Hwan Kim, Laurent D. Menard, P. R. C. Kent, Michael E. Woodson, J. Michael Ramsey, An-Ping Li, and Hanno H. Weitering. Nano Lett., Article ASAP, Online July 31, 2013, DOI: 10.1021/nl401574c.

β-Turn Sequences Promote Stability of Peptide Substrates for Kinases Within the Cytosolic Environment. Shan Yang, Angela Proctor, Lauren L. Cline, Kaiulani M. Houston, Marcey L. Waters and Nancy L. Allbritton. Analyst, 2013,138, 4305-4311.