Research

Dr. Kelly's research focuses on improving biological processes primarily those processes which make biopharmaceuticals.  His research is experimental and computational in nature. Listed below are specific areas of interest:

  • Fermentation and Isolation of DNA plasmids for gene therapy and DNA vaccine applications

  • Use of Expanded Bed Chromatography for isolation and purification of medicinal proteins

  • Optimization of CHO cell culture and Harvest for production of Monoclonal Antibodies (Mabs)

  • Shear-induced degradation of biological macromolecules and cells

CFD mesh of bioreactor - top view
CFD mesh of bioreactor - top view

Numerical simulations of two phase (gas and liquid) flow are being pursued using Computational Fluid Dynamic (CFD) modeling. The simulations predict the breakup and coalescence of gas bubbles as they are sparged into the bottom of bioreactors and collide with each other and the spinning impellers. The results of our CFD model of gas holdup and oxygen transfer in a bioreactor are being compared to actual experimental data from our laboratory. The goal of this research is to use the CFD model to determine the optimum bioreactor configuration (i.e. sparger location etc…) for given operating conditions (RPM, type cell line..).

CFD mesh of bioreactor - side view
CFD mesh of bioreactor - side view
Bioreactor flow patterns
Bioreactor flow patterns
Disassembling our CARR centrifuge
Disassembling our CARR centrifuge

Plasmid DNA: Clinical trials for gene therapy products began in the 1990’s. Because of the safety issues surrounding the use of viral vectors, DNA plasmids are being considered as gene vectors With plasmid-mediated gene therapy, a medicinal gene, carried by a double stranded DNA plasmid, is administered to the patient. The gene codes for a protein that is either missing/defective (i.e. gene therapy) or is antigenic (i.e. DNA vaccine). Use of DNA plasmids in future gene therapy or DNA vaccine products is currently cost-prohibitive, mainly due to the expensive chromatography steps necessary for final product purification. The goal of this research is to explore novel and less expensive approaches to traditional chromatography.

CHO cells: Chinese Hamster Ovary Cells are a popular mammalian cell line used in the biopharmaceutical industry to make monoclonal antibodies. These cells are damaged by chemical and physical stresses during cell culture and harvesting. The goal of this research is to understand the degree to which bioreactor, centrifuge and filter design and operating conditions effect the damage of these cells.

Taking a sample of CHO cells
Taking a sample of CHO cells