Projects for Summer 2012
NSF Research Experience for Undergraduates (REU) Program in Micro/Nano-Structured Materials, Therapeutics, and Devices
Projects for Summer 2012:
Embryonic Stem Cell Derived Cardiomyocytes: Tissue Engineering of Cardiac Tissue (E. Lipke, Chemical Engineering):
Embryonic stem cell derived-cardiomyocytes (ESC-CMs) are a promising cell source for cardiac regeneration strategies and cardiac tissue engineering. In order for this to be successful, however, one must be able to consistently guide embryonic stem cell (ESC) differentiation into electro-physiologically mature cardiomyocytes. Micro- and nano-patterned materials are known to guide neonatal ventricular myocytes to form cell sheets (~3.8 cm2) that mimic the structure and anisotropic nature of native cardiac tissue and to induce structure-size dependent changes in gap junction expression (Fig.1). In this project, undergraduate research students will learn to create micro- and nanopatterned scaffolds using photolithography and UV capillary molding techniques and to initiate differentiation of mouse ESCs into ESC-CMs. Students will also learn cell culture techniques and use immuno-histochemistry and digital imaging analysis to assess changes in cell morphology and orientation over time, correlating these results with the underlying material micro- or nanostructure. They will also assess tissue function, comparing the effect of groove depth and width on the rate of action potential propagation across ESC-CM cell sheets.
Micro/Nano Particle Processing (S. Duke, Chemical Engineering)
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The ability to control the size, shape, surface, and composition of polymer particles allows the design of particles for therapeutic and materials purposes. A number of processes are available to create particles, e.g. spray processes and solvent/antisolvent systems, that provide a means of distributing drugs or active chemicals within polymer structures. Overall, my group explores new ways of making particles in spray systems by developing understanding of the particle precipitation and formation processes through high magnification and high speed visualization of transport phenomena. We analyze particles we produce with SEM and other techniques to relate the particle properties to the formation processes, particularly the nucleation and growth of particles. The REU fellow will learn particle production techniques and relate solvent selection (acetone, ethanol, others) to particle size for PMMA particles produced by supercritical antisolvent processes. REU fellows will employ visualization and measurement of jet break up lengths and spray drop size distributions and particle SEM analysis for formation of PMMA particles in supercritical carbon dioxide.
Liquid Crystalline and Rheological Properties of Inorganic Nanorod Suspensions (
V.A. Davis, Chemical Engineering):
The REU student will investigate how to make multifunctional materials by combining carbon nanotubes with natural biopolymers. For example, coatings made from single-walled carbon nanotubes (SWNTs) and lysozyme (LSZ) are both strong and antimicrobial. SWNTs were discovered in 1991, and are 100 times stronger than steel and have 1/6th the weight. Lysozyme is a natural antimicrobial enzyme found in hen egg white and even human tears. REU students will work on dispersing nanomaterials such as carbon nanotubes and silver nanorods in two natural biopolymers, lysozyme and DNA. They will make aligned composite coatings and fibers from the dispersions and characterize the resulting material properties. As part of their research, undergraduates will have the chance to independently learn to perform characterization techniques such as turbidimetric assays, UV-VIS spectroscopy, Raman spectroscopy, optical and electron microscopy techniques, and mechanical characterization methods.
Rapid Identification and Recovery of Radioactive or Toxic Metal Ions (Anne Gorden, Chemistry and Biochemistry):
Persistent health protection concerns surrounding the use of actinides have been thrust into the public consciousness along with fears of radiological weapons (a "dirty bomb") or the spread of contamination from a nuclear waste storage site. These problems are complicated by the fact that our understanding of the chemical nature of the
5f elements is still limited. The goal of this project is to develop fluorescent organic ligands that can be incorporated into materials for selective chemosensors for the actinides, in this case uranium. The knowledge base gathered here could be used the rapid identification and/or remediation of these radioactive metal ions at a contaminated site. The fundamental knowledge generated will support our understanding of the behavior of actinide chemistry including hard-soft interactions, selectivity, and reactivity. REU students will learn about organic synthesis in the preparation of the ligands, radiation safety for working with uranium and thorium salts in the preparation of metal complexes, and analytical methods using UV-Vis and fluorescence spectroscopy in characterization of metal complex formation, selectivity, and detection limits.
Understanding Microstructure/Property Relationships of Nanomaterials (B. Prorok, Materials Engineering)
Understanding how a material's microstructure and its evolution control the performance and reliability of engineering components has been one of the most important contributions of the field of materials science. Traditionally applied to materials with microstructural features (grain size) in the microscale regime, this understanding is now desired to be extended into materials with grain sizes in the nanoscale regime. These nanostructured materials hold the promise of becoming the next generation of engineered materials that possess both high strength and high ductility. The underlying characteristic of these materials is their nanoscale grain structure, which can impart a variety of extraordinary material properties. Despite remarkable achievements in the area, there is still a considerable lack of fundamental knowledge in relating how nanoscale microstructure influences material properties, particularly for thin films where nanostructured features are playing an increasingly important role in many micro and nanoscale technologies. For example, numerous recent trade magazine articles report on the issues concerning the reliability of thin films and microdevices. Many of these highlight the lack of fundamental knowledge in how thin film nanostructure influences material properties, particularly important for enabling their commercialization. This project is aimed at introducing undergraduate students to critical issues in microstructure/property relationships of nanomaterials. Particularly it will investigate the influence of nanoscale twins on the mechanical behavior of metallic thin films. REU students will become proficient using high resolution scanning electron microscopy (SEM) combined with electron backscattered diffraction (EBSD) to identify the twins and characterize their manifestation in the films nanostructure as well as be exposed to common microfabrication procedures. They will study grain sizes in the nanoscale regime and the influence of nanoscale twins on the mechanical behavior of metallic thin films. The students will gain training in challenging new technologies that have a rapidly growing demand and introduce them to cutting-edge tools and techniques for advanced research.
Novel Magnetic Shape Memory Polymers (M. Auad, Polymer and Fiber Engineering)
Shape memory polymers (SMPs) are adaptive (or "smart") materials, which possess the ability to reassume their original shape following temporary deformations. Such a function is activated via external stimuli, such as temperature changes, and usually involves physical contact between SMP and the agent that induces the alteration. This project aims at preparing novel shape memory polymers able to experience form/volume changes when exposed to magnetic fields. This development in shape memory polymers promises to pave the way for many interesting new applications, especially in medical technology. The resultant polymer will be deformed simply by the application of a magnetic field without any direct contact with the material. The strategy is based on the inductive heating experienced by magnetic materials when they interact with a time-varying magnetic field. Thermoplastic polyurethanes functionalized with covalently bound magnetic nanoparticles of magnetite iron oxide will be used as SMPs. REU fellows will study the synthesis of magnetic-SMPs with controlled shape memory behavior and evaluate the effects of the magnetic particles on the SMP final morphology and properties. They will learn polymerization reaction and physical/mechanical polymer characterization techniques.
Controlling Microenvironments for Stem Cell Differentiation on an Integrated Microfluidic System (Jong Wook Hong, Materials Engineering)
This project combines state of the art nano/microfluidics and biotechnology and will give participating undergraduate students a unique chance to contribute to cutting-edge technology development. This work involves the synthesis and study of high-throughput microfluidic systems to study stem cell differentiation. Embryonic stem cell (ESC) differentiation is a potentially powerful approach for generating a renewable source of cells for regenerative medicine and biomaterials. It is known that the microenvironment greatly influences ESC differentiation and self-renewal. Most biological studies have aimed in identifying individual biological molecules and signals. However, it is becoming increasingly accepted that the wide array of signals in the ESC microenvironment interact in a synergistic and antagonistic manner based on their temporal and spatial expression, dosage, and specific combinations. REU students will participate in developing a high-throughput microfluidic based system that overcomes many of these challenges. They will help develop a microfluidic device to measure markers of stem cell differentiation as well as control differentiation. They will learn device fabrication, cell culture, and cell differentiation as well as small-scale characterization techniques.
Nanostructural Materials and Applications in Packaging and Storage of Food and Biological Materials (O. Fasina, Biosystems Engineering)
Nanostructural materials are naturally occurring or human made materials with nanoscale size or surface features that yield unique properties at the macro scale. One naturally occurring nanomaterial is montmorillonite - a natural smectite clay. It has been claimed that addition of 3-5% montmorillonite to plastics makes them lighter, stronger, and more heat-resistant as well as providing improved barrier properties against oxygen, carbon dioxide, moisture and volatiles. However, these enhanced properties of the nanocomposite has not been documented for packaging and storage of food and biological materials. In this project, undergraduate researchers will investigate (i) the moisture barrier properties of packaging films embedded with various levels of nanomaterials when used to store different products and (ii) the physical characteristics (texture and density), thermal behavior, and chemical stability of the films. The effect of storage temperature will also be investigated. During the course of experimentation, REU students will learn to use laboratory equipment such as a texture analyzer, pycnometer, thermogravimetric analyzer, fourier transform infrared and near infrared spectrometer, atomic force microscope, automated particle size analyzer, rheometer, and differential scanning calorimetry.
Pharmaceutical Nanoparticles (R. Gupta, Chemical Engineering):
Many of the side effects of pharmaceuticals can be reduced or eliminated if the drugs are targeted to the desired place in the patient's body. For example, if an arthritis drug only reaches the affected joints then the drug toxicity will not be encountered by the kidneys and the central nervous system. Dr. Gupta's research group, in collaboration with pharmacists and doctors, is developing smart drug formulations that reach the target site. Most of these formulations are based on the drug nanoparticles produced by supercritical antisolvent technology. To impart smartness to the nanoparticles, either nanosize magnets are imbedded in the particles or proper antibodies are attached on the surface. The REU fellow will have a choice of several small projects which can be completed in the summer session alone. Examples include: "Solubility in supercritical carbon dioxide", "Particle precipitation from supercritical solutions", "Particle precipitation by supercritical antisolvent", "Measurement of the drug release kinetics", etc. Each student will be exposed to a number of a number of experimental techniques as well as receive safety training on how to work with high pressure carbon dioxide. The REU fellow will learn to produce nanoparticles from supercritical solutions and learn particle characterization techniques, measurement techniques of drug release, as well as kinetic modeling of drug release.
Nanoparticle Reinforced Nanofibrous Structures (S. Adanur, Polymer and Fiber Engineering):
Nanofibrous structures are being used more and more in different applications with the advantages that micro and macro fiber structures do not offer. Our research group is exploring new manufacturing methods and designing new products to meet these needs. REU students will develop and characterize nanofibrous structures containing nanoparticles using electro spinning processes. The purpose of the proposed work is to improve the flame and heat resistance properties of current fibers by inclusion of nanoclays and carbon nanotubes. REU students will use spinning equipment to produce and study nanoclay and carbon nanotube reinforced nanofibers. The resulting fibrous structures will have interesting properties and can be used for different applications such as filtration, batteries, drug delivery systems, and safety and protection systems. The figure shows a typical nanofibrous structure obtained with a prior NSF REU Fellow. Undergraduate researchers will investigate the production of films of varying thickness directly from nanofibers where the permeability of these films can be changed based on thickness and density. Different polymer matrix materials will be also used.
Therapeutic Contact Lenses: Thin Film Medical Devices with Controlled and Extended Therapeutic Release (M.E. Byrne, Chemical Engineering):
Biomimetic and biohybrid materials are prime candidates for the creation of enhanced delivery systems with tremendous promise to profoundly impact medicine via improved treatment options for disease and better quality of life. Within the field of advanced drug delivery, major emphasis is now being focused toward engineering the architectural design of biomaterials at the molecular level. This work involves the creation and study of novel drug delivery materials developed using biology as a guide. Emerging areas of this technology involve micro/nanoscale films and therapeutic release platforms such as ocular delivery films, injectable carriers, and wound healing materials.
Enhanced drug loading and extended release in polymer gels can be achieved by biomimetic templating techniques, which involve the formation of a pre-polymerization complex between the template therapeutic and functional monomers by non-covalent chemistry. Our recent work demonstrates substantial differences in therapeutic diffusion coefficients from recognitive hydrogels with similar structure and mesh size. Creating molecular memory within polymer chains can significantly delay drug release and increase drug loading compared to conventional methods. Results indicate that the decreased diffusion of drug within recognitive gels is not due to significant differences in structural parameters but due to the tuning of the chemical functionality and macromolecular memory within the polymer film. Characterization analysis of the network structure of the hydrogel carrier in terms of molecular weight between crosslinking points, mesh size, polymerization reaction, and diffusion studies will provide an aid to optimizing the design and will begin to answer fundamental questions on the nature of the recognition and extended delivery in templated hydrogels on the chain level. Within our lab, recognitive hydrogels have been used to create novel therapeutic contact lenses, which can deliver therapeutic amounts of medication to the eye for an extended period from days to weeks. REU fellows will learn to synthesize 80 µm contact lenses with engineered architecture for one therapeutic. The focus will be to optimize an existing system studying a number of compositional variables. The student will learn skills in polymer synthesis and characterization as well as drug release modeling and kinetics. This new class of recognitive biomaterials is designed by incorporating motifs with structural and molecular homology to biological receptor docking sites and has a strong potential to work with a wide spectrum of drugs and impact the administration of a number of ocular therapies. The US prescription ophthalmic drug market, in which 90% is controlled by the eye drop and ointment sector, is approximately $4.5 billion and growing at a 10% average annual growth rate since 2002.
Shape-Controlled Synthesis of Metal Nanocrystals Through Expitaxial Seed-mediated Growth (C. Roberts, Chemical Engineering):
Morphological control of nanocrystals has become increasingly important, as many of their physical and chemical properties are highly shape dependent. A fundamental and technological emphasis has recently been placed on the control of nanoparticle shape, because in many cases it allows one to fine tune the properties with a greater versatility than can be achieved otherwise. To date, the challenge to synthetically and systematically control the shape of metal nanostructures has been met with limited success. As such, a development of a general method for the preparation of metal nanostructures with a broad range of well-defined and controllable morphologies is needed in order to fully exploit their distinctive properties and unique applications. Also, improved understanding of the mechanisms by which the shape of the nanocrystals can be controlled is needed. The objective of this project is to investigate selective/precise shape-controlled synthesis of metal nanocrystals using an expitaxial seed-mediated growth method. Through this seed-mediated process, metal nanocrystals are used as seeds on whose surface the secondary expitaxial growth occurs upon introduction of additional metal salts. The use hexadecylcetyltrimethyl (CTAB), as a template, along with the weak reducing agent ascorbic acid facilitates the shape-controlled synthesis of metal nanocrystals. The experimental conditions under which the different shaped metal nanocrystals, such as spherical particles, nanorods, and nanocubes, are selectively synthesized will be explored and optimized. In addition, the underlying mechanisms that govern the shape evolution will be systematically investigated. The REU fellow will learn to synthesize metal nanocrystals and optimize the experimental conditions under which different shapes (spheres, rod, cubes, etc.) form. The REU students will perform these experiments by employing statistical design of experiments techniques and will be exposed to a number of experimental procedures including the use of UV-VIS spectroscopy, FT-IR spectroscopy, transmission electron microscopy, and scanning electron microscopy, etc.
Evaluation of In Vivo Release of Analgesic Drugs in Rats via Microspheres and Nanoparticle Platforms (W. Ravis, Pharmacal Sciences)
Previous studies have formulated PLGA and polymer based microspheres and nanoparticles designed to release drug over periods of 30 to 120 days. Drug release rates in controlled in-vitro dissolution conditions are generally slower than that noted following dosing to animals. By varying the composition, drug to polymer ratio, and preparation technique, microsphere preparations with varying degrees of initial and prolong release amounts and periods have been formulated. REU fellows will examine the release and absorption of one narcotic and one non-narcotic analgesic following subcutaneous and intramuscular administration in a rat model. They will also acquire skills in pharmacokinetic modeling as well as in-vitro/in-vivo correlation. Three formulations of each product will be injected by either route and the appearance rate of drug and metabolites in the urine will be determined with respect to time. Pharmacokinetic analysis of excretion rates should provide estimates of in vivo release rates of the parent drug. The relationship of in-vivo to in-vitro release will be evaluated as well as the effects of route of administration.
Polyethylene oxide-Halloysite Nanocomposite Fibers and Membranes as Controlled Release Devices (E. Davis, Polymer and Fiber Engineering)
The objective of this work is to test the hypothesis that polyethylene oxide (PEO) - halloysite nanocomposite fibers and membranes can be produced and used as controlled release devices. We have recently demonstrated the ability of halloysite to mediate the release of tetracycline from polyvinyl alcohol films. The next step is to develop processes necessary to spin fibers containing halloysite tubes impregnated with active ingredients. Two processes are of interest, solution and electrospinning. The REU fellow will optimize the solution spinning process with respect to fiber diameter and drug release characteristics for PEO - halloysite nanocomposites. Students will learn how modifications to the fiber spinning process affect the microstructure of the spun fibers and, as a result, the properties of the release device. Controlled release kinetics and processing conditions will be studied as well as various structure characterization techniques. Potential parameters to be explored include, surface modification of the halloysite tubes (adsorption on the surface and within the lumen of the tubes), processing conditions (extrusion temperature, extrusion speed, and choice of solvent for the spinning bath), and spinning solution composition (concentration of halloysite and PEO). REU students will learn a number of characterization techniques such as microscopic analysis of the resulting fibers to evaluate orientation of the nano-tubes (SEM, AFM and TEM), material property characterization (tensile strength, elongation, etc.), and performance characterization relating to the kinetics of controlled release.
