Example Project Descriptions:
Analysis of internal mobility and exogenous stabilization of proteins
Dr. Jennifer Laurence
Our research focuses on understanding how the inherent mobility and stability of a
protein correlates with its therapeutic efficacy after lyophilization
(freeze drying) and rehydration. A number of pathways can diminish a
protein's efficacy, including denaturation (unfolding of the protein
structure), aggregation and chemical modification or breakdown. Our
research is aimed at understanding the driving force behind irreversible
denaturation during these processes. Our lab uses a broad range of
physical and spectroscopic methods of analysis to characterize protein
stability. High-field, multidimensional solution NMR is used for
structure determination and to assess internal dynamic motion.
Excipients (stabilizers) are commonly added to a protein solution prior
to freezing to prevent degradation. Nonetheless, changes continue to be
observed in proteins after long term storage, which abrogate their
therapeutic value. Our hypothesis is that the internal mobility of the
protein is a primary determinant in long-term stability of lyophilized
samples. Understanding how internal dynamics overcome the ability of an
excipient to stabilize a protein will provide insight for improving
formulations.
Enzyme Catalysis and Engineering of Pharmaceutical Intermediates
Dr. Aaron Scurto
Enantioselective (chiral) catalysis is extremely important in the pharmaceutical, agricultural chemical, and
specialty chemical industries. Chiral Sulfoxides are the active
functional group in one of the best selling pharmaceuticals of all time,
Nexium (the purple pill). Enzyme catalysis is becoming increasingly
employed in industrial processes, because enzyme are some of the most
efficient, selective, and environmentally benign catalysts known. This
project will investigate the ability of the Peroxidase class of enzymes
to perform chiral sulfoxidations on a variety of synthetically useful
substrates. Recent research has shown that enzymes have also the
ability to perform reactions in nonaqueous solvents and depending on the
solvent can actually be used to increase the enantioselectivity over
water based systems. This aspect of solvent engineering, which includes
new environmentally-benign solvents such as Ionic Liquids and
Supercritical Fluids, will also be employed to optimize the enzyme
process and allow the use of water-insoluble substrates.
Reaction/separation schemes will be designed to best perform the
reaction and separate the product to aid in industrial transfer. The
macroscopic results will be used to infer the dynamics and structure of
the protein at the molecular scale. Students will learn about enzymes,
chiral chemistry and catalysis, chiral and bio separations and analysis,
solvent engineering and protein binding.
Prediction of Kinetic Parameters for Peptide Drug
Stabilization
Dr. Kyle Camarda
This project seeks to apply computational molecular
design techniques to the problem of designing polymers to stabilize
peptide drugs. Current research in the laboratory of Prof. Elizabeth
Topp is evaluating the use of short-chain polymers as stabilizing agents
for peptide drugs, which often have very short shelf lives. The
degradation of these drugs often occurs via a deamidation reaction at a
specific site on the peptide. In order to design a polymer which
inhibits this reaction, a set of property prediction equations must be
developed which allow the prediction of the rate of the deamidation
reaction under specific conditions. The goal of this project is to
derive a model which can effectively predict the rate of this reaction,
based on structural information for the polymer-peptide system. This
project will design such a model by using experimental data from the
laboratory of Prof. Elizabeth Topp, and correlating this data with
structural descriptors such as connectivity indices. The resulting
model will then be used within an optimization framework to find novel
polymer structures which will be effective in stabilizing peptide drugs.
Genetic Algorithms for the Molecular Design of Gene Delivery Vehicles
Dr. Kyle Camarda
A major new emphasis within our research group is in
the design of polymers and other molecules which could surround a DNA
strand (forming a complex) and transfer that DNA to the nucleus of a
cell within the body. These polymers, called gene delivery vehicles,
have the potential to allow the reprogramming of cells, and thereby
provide new treatment options for cancer and many other ailments. This
project seeks to predict the properties of polymer-DNA complexes, and
will apply an optimization method called Genetic Algorithms (GAs) to
design polymers which will be effective at transfecting cells with
DNA. GAs start with a set of initial structures, and evolve them into
forms which match target values of physical and biochemical properties
needed for this biomedical application. The student will write a GA
program, test it on known problems, and then apply the program to design
problems for gene delivery vehicles. This project will be completed in
conjunction with Prof. C. Russ Middaugh in the Department of
Pharmaceutical Chemistry at KU.
Plasma Etching of
Compound Semiconductors
Dr. Karen J. Nordheden
Plasma etching is a key processing step in the
manufacture of semiconductor devices. It involves the selective removal
of materials using chemically reactive gases such as chlorine, boron
trichloride, silicon tetrachloride, and sulfur hexafluoride. The
formation of a plasma in these gases provides the mechanism to
dissociate the parent molecule in order to liberate atomic chlorine or
fluorine (which are the main etch species). Current work in the Plasma
Research Laboratory is focused on the development of etch processes for
GaAs, GaN, SiC, and ZnO based devices. The student would be working
with graduate students as a member of the research team and will be
introduced to the use of the Plasma Therm Reactive Ion Etching system,
as well as various diagnostic techniques such as mass spectrometry,
optical emission spectroscopy, and Langmuir probe/microwave phase
measurements of electron density and temperature.
Drug Delivery
Dr. Cory Berkland
As complex and potent new drugs are developed at a rapid pace, new
techniques have become necessary to deliver these drugs to the right
place, at the right time, and in the correct amount in the human body.
Using physical and/or chemical methods to encapsulate drugs provides a
means to protect and target drugs, thus increasing drug effectiveness
and reducing the potenial for harmful side effects. Our lab studies
micro- and nanoencapsulation of small molecule drugs and proteins into
biodegradable polymers. We devise new and unique techniques promoting
the retention of drug activity while enabling efficient delivery
schemes. Many projects are open including; pulsed antigen delivery for
one-shot vaccine development, circulating nanoparticles for targeted
therapy, nanogels for protein stabilization and delivery, engineered
porous particles for improved inhalation therapy, and microfabricated "patchless
patch" transdermal drug delivery.
Heterogeneous Catalysts for the Production of Alternative Fuels
Dr. Susan Stagg-Williams
The heterogeneous catalysis research
facility of Dr. Susan Stagg-Williams at the University of Kansas is
currently studying the use of oxygen permeable membrane reactors and
traditional powdered catalysts for the autothermal reforming of methane,
the low temperature water gas shift, and carbon monoxide oxidation
reactions. The reactions are the primary reactions involved in the
production of hydrogen and we are investigating the activity and
selectivity of various heterogeneous catalyst systems at atmospheric
pressure for use in fuel cell applications. The generation of hydrogen is
a limiting factor in fuel cell technology. Production of H2
from hydrocarbons is currently achieved in the chemical industry for
ammonia and alcohol production using carefully controlled catalytic
processes. However, each process unit has limitations that prevent their
application in fuel cell technology for mobile and stationary sources.
These limitations include high pressures, expensive oxygen separation
units, and pyrophoric or self-heating catalysts. The proposed research
program is aimed at developing alternate catalytic systems that overcome
these technological barriers. Additional work in the production of
biodiesel using heterogeneous catalysts is also being explored.
Polymer gels used in enhanced oil recovery
Dr. Don W. Green
This project involves the study of polymer gels, which can be formed in
porous media by the crosslinking of a high molecular weight polymer with a
metal ion. The permeability of these gels is low and they are capable of
reducing the flow of water substantially through the regions contacted by
the gel. Projects range from the study of kinetics of gelation to the
dehydration of gels after placement when exposed to pressure
gradients from water or oil. One goal of the program is to improve methods
of increasing the volumetric sweep of waterfloods by selective placement
of gelled polymer systems that reduce the flow of water through high
permeability regions. A second goal is to reduce the water flow in
production wells that are producing at high water cut.
Coalbed Methane Production
Dr. Russell D. Ostermann
Coalbed methane accounts for about 8% of U.S. natural gas production.
This fraction will probably rise. One area we are looking at is
environmentally friendly fracturing fluids. Coalbeds must be
hydraulically fractured prior to production. Water thickened with
additives used for oil field application is used for this process.
In a typical oil application, the injection zone is well below any surface
aquifer zones. With coalbeds, this is often not the case. With
the oil field fluids, since they are deep injected, environmental concerns
are minimal. With coalbeds, new fluids are needed which will not
pollute sensitive surface aquifers.
An additional project has to do with biological production of methane
from coal and carbon dioxide. We are looking at nutrients to enhance
the natural biological process, and pretreatments to render coal more
susceptible to biological attack.
Biomedical Engineering Time Release Material Development
Dr. Marylee Southard
Marylee Southard's research interests are in the design and analysis of
chemical transport processes, specifically those in which bioactive agents
are released. This research area is multidisciplinary in nature because
workers in other disciplines usually define the chemical of interest and
the problems associated with its movement. Her usual role (and interest)
in a collaborative venture is to analyze mathematically the desired and/or
existing mode of release and to design a novel means of achieving or
altering that mode. Numerical methods and software are used as tools to
simulate chemical transport in diverse types of tissue, across membranes
and other barriers. Cellular growth, metabolism and carrier-mediated
uptake are also simulated mathematically to mimic the in vivo environment.
Simulation of behavior in a given environment allows collaborators to
optimize of the number of experiments required to design an optimal
chemical formulation or diagnostic device. Dr. Southard's ultimate goal in
this work is to enhance understanding of biological processes as related
to drug therapies, disease states, and pathological conditions.
Fuel Cells
Dr. Trung Nguyen
Fuel cells and batteries and mathematical modeling of electrochemical
systems. Current focus is in:
- Interfacial phenomena at the electrode/membrane and
membrane/membrane interfaces.
- Theoretical and experimental studies of spatiotemporal behavior and
two-phase transport in porous electrodes and flow channels in PEM fuel
cells.
- Heat, gas and water management in proton exchange membrane fuel
cells
- Development of high performance electrode and membrane assemblies
and flow field designs for PEM fuel cells.
- Thermal runaway in various sealed battery systems.
Proton Exchange Membrane Fuel Cells
Due to the simplicity of its design and operation, the PEM fuel cell
system is gaining great interest in terrestrial applications such as power
generation and transportation. Efforts in recent years have resulted in
substantial progress in the area of catalyst loading reduction and
membranes with improved conductivity, water permeability and thermal
stability. The principal remaining feature hindering the commercialization
of this system is its ability to be operated at high power density with
high energy efficiency. Recent work has shown that proper water and
thermal management and elimination of electrode flooding in the cathode
are the keys to achieving improvements in this area. These two challenges
constitute the main focus of my research. Experiments are being conducted
to investigated the effectiveness of various heat and water management
strategies, flow field designs, electrode configurations and supported and
unsupported catalysts formulations and preparation techniques.
Mathematical models are being developed to understand the effects of
two-phase flow and the complex interaction of thermal and mass balances
involved in this system. These models are also being used to explain the
recently observed spatiotemporal behavior in the fuel cell cathodes at
high current densities. Results will be used to develop optimal heat, gas
and water management systems and electrodes with better flooding
resistance. Major Funding Sources: NSF, DOE and The University of Kansas
Graduate Research Fund.
Thermal Management Problems in Valve-Regulated Lead-Acid Batteries
The lead-acid battery industry is moving rapidly toward sealed, valve
regulated lead-acid (VRLA) batteries for a number of reasons: high power
density, claims of superior safety and minimal loss of gas, freedom from
acid spillage, and the claim of "maintenance free. Unfortunately for the
users, the unique characteristics that give this new system its
advantageous over the flooded system also introduce new operational
problems: premature dryout and thermal runaway in high ambient temperature
operation. To help solve these problems, my research group is developing
various models that can be used to identify design characteristics that
are more prone to thermal runaway and to assist in the development of more
thermal runaway-resistant VRLA batteries.
Links to Research Group(s)
Process Design for Minimization of Emissions
Dr. Colin Howat III
My primary research interests are concerned with the design and
operation of chemical process units. The first fundamental aspect of my
work involves the assembly of the database needed to design new processes
for separating azeotropic and isomeric mixtures and for removing volatile
organic chemicals from wastewater contaminated with organic solids. The
operation-oriented aspect of my work involves the development of numerical
methods to analyze properly industrial plant operation, to determine plant
sensitivity to the fundamental data upon which it is based and to predict
the reliability of a process to meet its objectives subject to
uncertainties in the principal parameters.
Separating azeotropic and isomeric mixtures on an industrial scale is
costly. Sound phase equilibria data are required for the accurate
development of economic process designs. The measurement and analysis of
the phase equilibria with the experimental designs soundly rooted in
industrial end-use criteria is one aspect of my work.
The separation of the volatile organic chemicals (VOC's) from
wastewater and from water bearing latex streams is becoming
environmentally important. This separation is particularly difficult due
to the presence of organic and inorganic solids in the wastewater.
Development in two areas is required. First, fundamental measurements in
the infinite dilute region are required. Second, a thermodynamic model
capable of describing the adsorbed, liquid and vapor phases suitable for
process design applications is required. The experimental effort required
to assemble the data base and to evaluate the thermodynamic model is
supported by equipment capable of measuring temperatures to 0.01K,
pressures to 0.01 kPA and mole fractions to 1 part in 1000 at 1e-4 mole
fraction.
The control and on-line optimization of an industrial chemical process
unit require an accurate mathematical model of the process. Plant
performance analysis is the proper identification, rectification,
reconciliation and interpretation of plant operating data. The goal of the
analysis is to improve operations, process control, safety and
profitability. The development of a proper plant performance analysis
procedure firmly rooted in statistics, recognizing plant measurement
uncertainty, is another aspect of my research work. The statistical and
theoretical develop is supported by having a fully operational pilot plant
in the laboratory facilities.
The uncertainty in the design and operation of a chemical plant is
related to the uncertainty in the fundamental database that was used to
design the plant. The design-data relationship had received little
research attention even though entire plants as well as individual pieces
of equipment have failed to operate as designed because of uncertainties
in the database. Proper sensitivity analysis in the area of computer-aided
design should become a part of the process design procedure. Further,
process operating parameters along with uncertainty in the underlying data
base affect the reliability of process units to meet capacity, recovery
and purity requirements. Estimation of reliability is hampered by the
complexity of process simulation mathematics. Development of sensitivity
analysis and design reliability criteria is another aspect of my research
interests.
My research program is founded upon a background in phase equilibria,
statistics and industrial process design; and it addresses primarily
industrial needs with the goal of improving engineering technology and
plant economics.
Links to Research Group(s)
Kurata Thermodynamics Laboratory
Environmentally
Benign Catalyst Development
Dr. Bala Subramaniam
Research Interests
Kinetics and Catalysis, Near-critical Processing, Mathematical
Modeling.
Exploiting Supercritical Fluids in Heterogeneous
Catalysis
During the last decade, supercritical fluids (such as supercritical
carbon dioxide and supercritical water) have been increasingly explored
for performing a variety of catalytic reactions such as hydrogenations,
alkylations, aminations and oxidations, to mention a few.
Adsorption/desorption and pore-transport are key parameters influencing
the activity, effectiveness factors and product selectivity in porous
catalysts. With conventional reaction media (either gas or liquid phase),
one of these parameters is generally favorable while the other is not. For
instance, while desorption of heavy hydrocarbons from the catalyst is
usually the rate-limiting step (and therefore detrimental to catalyst
performance) in gas-phase reactions, transport of the reactants/products
is the limiting step in liquid-phase reaction media. Furthermore, with
conventional media, it is usually difficult to achieve the desired
combination of fluid properties for optimum system performance. In
contrast, density and transport properties can be continuously
pressure-tuned in the near-critical (nc) region to obtain unique
fluid properties (e.g., gas-like transport properties, liquid-like solvent
power and heat capacities), that offer several advantages such as these:
- The in situ extraction of heavy hydrocarbons (i.e., coke
precursors) from the catalyst surface and their transport out of
the pores before they are transformed to consolidated coke, thereby
extending catalyst lifetime;
- Complete miscibility of reactants such as hydrogen in the reaction
mixture and enhanced pore-transport of these reactants to the catalyst
surface, thereby promoting desired reaction pathways;
- Enhanced desorption of primary products, thereby preventing
secondary reactions that adversely affect product selectivity; and
- Control of temperature rise in exothermic reactions, thereby
preventing "reactor runaway" conditions.
Experimental and theoretical investigations are underway to demonstrate
pressure-tuning effects on catalyst activity and product selectivity
during continuous processing of a variety of reactions such as these:
geometric isomerization and alkylation on solid acid catalysts; Fischer-Tropsch
synthesis on supported Fe catalysts; and fixed-bed hydrogenation on
supported catalysts. The possibility to use dense phase CO2 as
replacement for conventional solvents, to create compressible reaction
mixtures perform solid acid catalysis with extended activity (an
environmentally safer alternative to liquid acid processes) and fixed-bed
hydrogenations with tunable selectivity and controlled temperature rise
(preferred over slurry phase operation) makes nc reaction media
particularly appealing alternatives to conventional reactor operation.
Catalytic Oxidations in Dense Carbon Dioxide-Based
Reaction Media (with Professor Daryle Busch of the Department
of Chemistry, University of Kansas)
This research program seeks a complete understanding and ultimate
exploitation of homogenous catalytic oxidation chemistry in dense phases
of carbon dioxide. A major advance and the focus of current research is
the discovery and demonstration, in these laboratories, that CO2-expanded
solvents are highly desirable media for homogeneous catalytic oxidations.
The research program exploits these unique media and a successful
perspective on catalyst design to develop new environmentally benign
homogeneous transition metal catalyzed oxidation systems for such chemical
reactions as olefin epoxidation, functional group oxidation, and bleach.
The new medium, CO2-expanded solvent, is produced by
increasing the volume of the solvent (that is soluble in CO2)
through the addition of relatively large amounts of CO2. Each
CO2-expandable solvent can, in principle, generate a continuum
of media ranging from the neat organic solvent to neat CO2.
Thus, the solvent properties may be varied to accommodate contrasting
solubilities simultaneously, like those of oxygen and catalysts based on
metallic elements; a large amount of CO2 favors oxygen
solubility and polar organic solvents favor metal catalyst solubility. We
have demonstrated that the beneficial physical properties may be elegantly
combined in CO2-expanded reaction mixtures to perform a variety
of homogeneous catalytic oxidations. Reaction advantages are:
- Higher oxygen miscibility (up to two orders of magnitude) compared
to organic solvents.
- Applicability to transition metal catalysts without ligand
modification (e.g. no environmentally non-benign fluorination to enhance
their solubilities).
- Between one to two orders of magnitude greater TOFs and either
comparable or better product selectivities than in neat organic solvent
or scCO2.
- Following the reaction cycle, the catalyst may be separated from the
reaction mixture by simply adding more CO2. The catalyst-free
reaction mixture may then be subjected to stepwise pressure reduction to
effect the separation of product(s) and remaining reactants.
Environmental and economic advantages include the following:
- Substantial (up to 80 vol.%) replacement of organic solvents with
dense-phase CO2,
- Milder process pressure (tens of bars) compared to scCO2
(hundreds of bars),
- With substantial CO2 expansion, explosive mixtures can be
avoided in the presence of oxygen and other potent oxidants. Thus,
oxidation in CO2-expanded solvents is inherently safer than
in traditional solvents.
- Enhanced reaction rates and low process pressures give favorable
process economics.
Our current foci include: (1) the iterative optimization by molecular
design of known and new homogeneous catalyst systems for oxidations in
dense phase CO2 media; (2) the incorporation and evaluation of
outstanding catalysts in aqueous or other media that may become
co-solvents, intravesicular solvents, or otherwise partnered with dense
phase CO2; and (3) Modeling of CO2-expanded solvent
media complemented by detailed mechanistic studies of selected catalytic
reactions.
Pharmaceutical Processing with Dense Phase Carbon
Dioxide
Replacement of traditional solvents with sc carbon dioxide
(because of its pressure-tunable physical/transport properties and
environmentally-benign nature) is receiving increased attention in
pharmaceutical processing. Among the applications, particle micronization
(to increase drug bioavailability) and coating of drug compounds (for both
aesthetic as well as functional reasons) using sc carbon dioxide as
the processing medium hold promise for large-scale application.
Spray processes employing sc CO2 (Pc =
72.8 atm; Tc = 31.1°C) as an anti-solvent are well known. In
this method, the solute is solubilized in an organic solvent. The solution
is then sprayed into a chamber containing sc-CO2, which
selectively solubilizes the solvent from the spray droplets, causing the
solute to precipitate as microparticles. In an ongoing joint research
effort with the Center for Drug Delivery Research at the University of
Kansas, investigations are underway aimed at a fundamental understanding
of how process variables (such as nozzle design, spray solution rate,
antisolvent flow rate, etc.) affect particle size distribution,
crystallinity, bioactivity, etc. Such an understanding is essential for
rational design and scale-up of this promising technology in
pharmaceutical practice.
In a parallel effort, we have developed a continuous coating process in
which the drug-laden solution is sprayed on beads or tablets (coating
substrates) suspended in sc CO2. The sc CO2
also acts as an antisolvent for the drug selectively solubilizing the
solvent from the spray droplets. The resulting drug particles are
deposited (i.e., coated) on the substrate. Using this technique, we have
successfully coated glass, non-pareil sugar and alumina beads with
polymers (such as ethyl-cellulose and PLGA copolymer) and drugs (such as
hydrocortisone). This process complements the conventional Wurster coater,
expanding the range of substrate-drug combinations. Our goal is to develop
a fundamental understanding of the effects of operating parameters such as
pressure, temperature and spray-rates on coating morphology and
uniformity. Such an understanding is essential for rationally developing
coating applications of interest to the pharmaceutical industry.
