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

Fluorous Enzymatic Synthesis

As presented in Chemical Communications, researchers in the Allbritton Group in collaboration with Qisheng Zhang, associate professor in UNC's School of Pharmacy, and his group, have published a fluorous tagging strategy coupled with enzymatic synthesis to efficiently synthesize multiple phosphatidylinositides (PIs). PIs and their derivatives are notorious for their structural complexity, with seven stereogenic centers and the hydroxyl groups around the inositol head unit having similar reactivity.

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Most synthetic strategies require selective protection and deprotection of the hydroxyl groups, and usually take more than 15 steps to synthesize one PI. The work presented by the two groups introduces "fluorous enzymatic synthesis," where tandem enzymatic reactions are used to generate multiple probes after purification through fluorous solid phase extraction. These probes can then be used as enzyme reporters, or be directly immobilized on a fluorous surface to form a microarray to investigate protein-small molecule interactions. This strategy should also be applicable to other complex endogenous small molecules whose biosynthetic enzymes are well characterized.

 

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 greater or equal to 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.

 

Representative Publications

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.

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.