Research


        The primary goal of our research is to investigate the thermodynamic, transport, and biophysical principles that underlie separation processes for biological macromolecules and related types of materials. Another goal is to exploit this improved understanding in order to develop novel methods for both analytical-scale and process-scale separations. 

        Chromatofocusing.  One area of work has involved investigations of the technique of chromatofocusing. In one particular project, computational design methods are being developed to optimize the conditions so that stable mobile-phase composition gradients can be formed without using the polyampholyte buffers and proprietary weak-base column packings normally used for chromatofocusing. Such systems greatly expand the range of applications possible for the technique, including to peptide separations, to high-speed, high-resolution, and high-sensitivity analytical separations performed using capillary columns, and to various process-scale systems, such as those using expanded beds. In a related project we are developing a novel hybrid chromatography method that incorporates aspects of both chromatofocusing and displacement chromatography and that eliminates the need for a traditional displacer component for accomplishing displacement chromatography.

        Development and Characterization of Novel Chromatographic Column Packings.  Our work in this area involves the synthesis and characterization of novel types of column packings and the development of new characterization methods based on theories of chromatography. In one specific project we are developing novel mixed-mode column packings that exhibit both ion-exchange and hydrophobic interaction functionalities based on heterocyclic nitrogen functional groups. Another project involves the investigation of slurry packing methods for conventional, microbore, and capillary HPLC columns with the goal of increasing the performance of these columns.   

         Methods for Analyzing Complex Protein Mixtures.   Novel versions of 2D chromatography are being interfaced to various types of detectors to develop improved liquid chromatography methods for the analysis of complex protein mixtures. In one project high-resolution chromatofocusing performed using a micropellicular (nonporous particle) column packing is being interfaced to either ESI-MS or MALDI-TOF-MS to produce a technique that can replace standard two-dimensional polyacrylamide gel electrophoresis (2DE) for the routine characterization of protein molecular weight and isoelectric point. In another project we are investigating novel chromatographic approaches for performing native LC-MS of intact proteins.       

         Sorting of Carbon Nanotubes.  Chromatographic methods are being developed for the efficient, large-scale separation of metallic and semiconducting carbon nanotubes. This is being accomplished by the differential functionalization of the chiral forms of carbon nanotubes followed by the chromatographic separation of these chiral forms.

         Computational and Mathematical Studies of Separation Processes for Biomolecules.  Numerical and analytical mathematical methods are being applied to chromatography and related types of separation processes for biomolecules to gain a better fundamental understanding of these processes. In one study, mathematical theories of dispersion in porous media are being used to gain a better fundamental understanding of the factors governing chromatographic band broadening. In another study, data-driven machine learning, physics-informed machine learning, and various types of computational design methods are being developed for system identification and optimization of bioseparation processes. In addition, multiscale modeling as well as statistical mechanical perturbation theory are being employed to study the phenomenon of charge regulation when proteins adsorb onto a charged surface.   

         Protein Purification in a Point-of-Care Therapeutic Protein Production Device.  Purification methods are being developed that are suitable for producing single-doses of protein drugs on-demand with therapeutic grade purity at the point-of-care in a small-scale device.  

         Software Development.  We are a (sometimes) developer of open-source software packages for chemical engineering applications using the Julia programming language.  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

gfp imaging

 

       Visualization of viscous fingering inside a chromatographic

       column using a fluorescent probe.

 

 

 

 

2D-HPLC imaging

 

       Representation of 2D-HPLC for CHO cell lysate

 

 

 

 

binding imaging

 

       Monte Carlo docking simulations showing the preferred

       binding positions of a quaternary amine ligand on the

       surface of bovine beta-lactoglobulin A.

 

 

 

 

BioMOD image

 

       Device for small-scale, point-of-care production of

       therapeutic grade protein drugs.