Contact Information
tel: (610) 758-4257
fax: (610) 758-5057
e-mail: jth0@lehigh.edu

Research Interests

Bioseparation Processes

Proteins produced by genetically engineered microorganisms are of considerable interest for use as pharmaceuticals and as medical diagnostic reagents. The large-scale production of these proteins is, however, a difficult task because the proteins are unstable and difficult to separate. In addition, the biological activity of a protein depends critically on its three-dimensional structure that must be maintained during the purification. Finally, purification of a protein can be further complicated if crude starting material contains a large number of other compounds, particularly if some of them are very similar to the one of interest.

We are interested in bioseparations using selective precipitation and affinity adsorption. Understanding the chemistry and kinetics of precipitation is critical for the success of the large-scale process. Affinity adsorption employs the extraordinary selectivity of the antibody-antigen interaction for the recovery of a specific protein or other bioactive molecule. We investigate the selection of the antibody to be immobilized and its interaction with its support and target molecules.

Aqueous Two-Phase Polymer Systems

Aqueous, two-phase, liquid-liquid extraction using polyethylene glycol (PEG)-dextran systems is a promising separation technique for the recovery of biomolecules from complex mixtures, since they split uniquely between the two phases. A comprehensive correlation of polymer solution thermodynamics is being formulated to predict the phase diagrams. These data will be combined with a characterization of the interaction between biomolecules and the two-phase constituents to obtain a predictive correlation of the partition coefficients.

Chromatographic Separations in Industrial Processing

The separation of chemical and biochemical mixtures by chromatographic processes is increasingly important in industrial processing. Linear scale-up of chromatography columns, based on the ratio of sample volume/adsorbent volume, gives poor resolution because of channeling, wall effects, lower intraparticle diffusivities, different mass velocities, nonlinear adsorption isotherms or the compressibility of adsorbents. We are using mathematical modeling and experimental correlations for different types of chromatographies to improve resolution.

DNA Amplification by Polymerase Chain Reaction Engineering

Genetic vaccination and gene therapy is moving rapidly from the research laboratory to the clinics. Human clinical trials of direct in vivo transfer gene therapy or genetic vaccines require the development of scalable manufacturing processes that reproducibility meet the quality criteria of purity, potency, efficacy, and safety for a recombinant drug substance. Laboratory scale methods for the production of plasmid DNA have traditionally relied upon extractions with toxic organic solvents, ethidium bromide and cesium chloride gradient centrifugation and the use of animal derived enzymes such as lysozyme, proteinase K and ribonuclease.

To circumvent this contamination problem in large scale manufacture of purified DNA from recombinant DNA cells, is to scale up the polymerase chain reaction (PCR) process directly. The objectives of this project are to develop a comprehensive kinetic model for polymerase chain reaction, and to investigate the effects of transport processes on the reaction in order to design a reactor to scale up this polymerase chain reaction.