Sunday, February 07, 2010
8:00am - 1:40pm

Lecturers: Joseph M. DeSimone, Paolo Decuzzi, Martin Ostoja-Starzewski, Thomas Thundat, Jennifer West, Chun Li

Course Description and Outline
Module 1 - Presented by J. DeSimone:
Top-down Fabrication Technologies for the Production of Highly Uniform, Shape-Specific Carriers for Vaccines, Biologics and Small Molecule Drugs

To translate promising molecular discoveries into benefits for patients, we are taking a pharmaco-engineering systems approach to develop the next generation of delivery systems with programmable multi-functional capability. Our laboratory has pioneered the development of a technique called PRINT (Particle Replication in Non-wetting Templates). PRINT is a top-down particle synthesis method that extends the nano-fabrication techniques from the semiconductor industry to a high throughput, continuous roll-to-roll process. PRINT enables the fabrication of precisely defined micro- and nano-particles with control over particle size (20 nm to >20 micron), shape, chemical composition, cargo (proteins, adjuvants, therapeutics, oligonucleotides, siRNA, imaging agents), modulus (stiff, deformable - RBC mimics) and surface chemistries (antibodies, PEG chains, metal chelators), including the spatial distribution of proteins on the particle. In the history of delivery, particles have never had the uniformity, precision and chemical and shape control afforded by PRINT.

Module 2 - Presented by Jennifer West
Diagnostic and Therapeutic Applications of Nanotechnology

The increasing capability to manipulate matter at the nanoscale is generating new materials with unique properties that promise to address unmet medical needs for future generations. As an example, metal nanoshells are a relatively new class of nanoparticles with highly tunable optical properties. Metal nanoshells consist of a dielectric core nanoparticle such as silica surrounded by an ultrathin metal shell, usually composed of gold for biomedical applications. Depending on the size and composition of each layer of the nanoshell, particles can be designed to either absorb or scatter light over much of the visible and infrared regions of the electromagnetic spectrum, including the near infrared region where penetration of light through tissue is maximal. These particles are also easily conjugated to antibodies and other biomolecules for specific targeting. Further, the biocompatibility of these particles is excellent. One can envision a myriad of potential applications of such tunable particles. Several potential biomedical applications are under development, including immunoassays, modulated drug delivery, photothermal cancer therapy, and imaging contrast agents.

Module 3 - Presented by Chun Li
Nanotechnology Molecular Theranostics

For effective translation of new nanodevices to clinic, it is important to incorporate and integrate noninvasive imaging techniques into new treatment strategies. Another issue important for effective translation of new nanodevices to clinic is their efficient delivery to tumors in vivo after systemic administration. In my presentation, I will discuss targeted delivery of several forms of nanodevices, and discuss important factors that can influence the efficiency of active targeting. An in-depth understanding on how nanoparticle characteristics influence not only on their circulation and biodistribution, but also their extravasation and extravascular transport in the tumor, is a prerequisite for achieving targeted delivery of novel nanodevices. The applications of several class of nanoparticles in cancer diagnosis and therapy, including water-soluble polymeric drug conjugate and core-shell structured gold nanospheres, will be presented. In particular, I will describe a new class of molecular specific photothermal coupling agents based on hollow gold nanospheres (HAuNS, average diameter ~40 nm) covalently attached to monoclonal antibody and peptide ligands directed at tumor-surface receptors. These nanodevices cannot only be used for photothermal ablation therapy, but also serve as contrast agents for guiding therapy with photoacoustic imaging.

Module 4 - Presented by T. Thundat:
Nanomechanical Implantable Sensors for Diagnostics

Microfabricated cantilever platform integrates nanoscale science and microfabrication technology for label-free detection of biological molecules. Molecular adsorption, when restricted to a single side of a deformable cantilever beam results in measurable bending of cantilever. Biological specificity in detection is typically achieved by immobilizing selective receptors or probe molecules on one side of the cantilever using surface functionalization process. Recent progress in developing an implantable multi-analyte sensor will be discussed. We will address the many challenges facing the development of implantable sensor. We will also discuss novel techniques that do not use receptors for selectivity.

Module 5 - Presented by P. Decuzzi:
Rational Design of nano-Particle Systems for Biomedical Imaging and Therapy

Systemically administered particulate systems before reaching their ?nal target and execute their missions, have to make their way into the circulatory system, reach the diseased microvasculature, extravasate crossing the blood vessels, diffuse through the extracellular matrix (ECM) and eventually bind to the target cell. For particles designed to target the diseased vasculature, three issues are of importance: the margination dynamics, the strength of adhesion and the control of cell internalization. The term margination dynamics refers to the lateral drifting of particles towards the blood vessel walls, which facilitates the interaction with the diseased vasculature and allows eventually for ?rm adhesion, if speci?c conditions are met. The term strength of adhesion is referred to the ability of particles to attach ?rmly to the blood vessels withstanding the hemodynamic forces. Finally, the term internalization is referred to the ability of an adherent particle to control uptake by the host cell. A broad spectrum of particulate systems has been presented in the literature with different compositions, chemico-physical properties, sizes and shapes. On the other hand, Nature provides a variety of biological corpuscles with shapes which differ substantially from spherical. For example, red blood cells have a biconcave disc shape; platelets have an oblate spheroidal shape; the shape of most proteins as BSA, Fibrinogen, IgG deviates significantly from the spherical. The talk will review the most recent developments in the rational design of particulate systems, emphasizing the contribution of particle geometry (size and shape). Theoretical, in-vitro and in-vivo results will be presented and discussed.

Module 6 - Presented by M. Ostoja-Starzewski
Homogenization and Scaling Methods of Heterogeneous Media

Microstructural randomness is present in most solid materials, both natural and man-made. When the separation of scales does not hold, many concepts of deterministic continuum solid mechanics need to be re-examined and new methods developed. First, we review scaling from a Statistical Volume Element (SVE) to a Representative Volume Element (RVE). The RVE results from two hierarchies of bounds stemming, respectively, from Dirichlet and Neumann boundary value problems set up on the SVE. We discuss trends to approach the RVE in various linear and nonlinear/inelastic media. This methodology then forms the basis for micromechanically based continuum random fields and stochastic finite elements, with the key observation being that material properties of such elements have to be scale-dependent and may not be chosen by intuition. Transient response is another field where even weak material randomness may strongly affect conventional solutions of homogeneous media. For instance, considering an acceleration wavefront, we recognize that its thickness is not infinitesimal as conventionally done in the singular surface analysis, but finite. As a result, the wavefront’s evolution is governed by stochastic dynamics, with the ensemble average being generally different from the solution of the average problem based on homogenized coefficients. Time permitting we will allude to other stochastic mechanics problems lacking separation of scales: fracture, shape optimization, and fractal geometries

Lecturers

		Dr. Joseph M. DeSimone Professor of Chemistry University of North Carolina at Chapel Hill and William R. Kenan Jr. Professor of Chemical Engineering North Carolina State University. Joseph DeSimone is the Chancellor's Eminent Professor of Chemistry at the University of North Carolina at Chapel Hill and William R. Kenan Jr. Professor of Chemical Engineering at North Carolina State University. DeSimone has published over 240 scientific articles and has over 115 issued patents in his name with over 120 patents pending. In 2005 DeSimone was elected into the National Academy of Engineering and the American Academy of Arts and Sciences. DeSimone has received 38 major awards and recognitions including the $500,000 Lemelson-MIT Prize for Invention and Innovation; the 2008 Tar Heel of the Year by the Raleigh News & Observer; 2007 Collaboration Success Award from the Council for Chemical Research; the 2005 ACS Award for Creative Invention; the 2002 John Scott Award presented by the City Trusts, Philadelphia, given to "the most deserving" men and women whose inventions have contributed in some outstanding way to the "comfort, welfare and happiness" of mankind; the 2002 Engineering Excellence Award by DuPont; the 2002 Wallace H. Carothers Award from the Delaware Section of the ACS; 2000 Oliver Max Gardner Award from the University of North Carolina, given to that person, who in the opinion of the Board of Governors' Committee, ". . . during the current scholastic year, has made the greatest contribution to the welfare of the human race". Among DeSimone's notable inventions is an environmentally friendly manufacturing process that relies on supercritical carbon dioxide instead of water and bio-persistent surfactants (detergents) for the creation of fluoropolymers or high-performance plastics, such as Teflon®. In 2002, DeSimone, along with Dr. Richard Stack a cardiologist at Duke, co-founded Bioabsorbable Vascular Solutions (BVS) to commercialize a fully bioabsorbable, drug-eluting stent. BVS was acquired by Guidant Corporation in 2003 and these stents are now being evaluated in an international clinical trial for the treatment of coronary artery disease. DeSimone's group is now heavilyfocused on learning how to bring the precision, uniformity and mass production techniques associated with the fabrication of nanoscale features found in the microelectronics industry to the nano-medicine field for the fabrication and delivery of therapeutic, detection and imaging agents for the diagnosis and treatment of diseases. Particular focus for PRINT is the targeted delivery of biologicals, such as mABs and siRNA, to intra-cellular targets. DeSimone recently launched Liquidia Technologies (www.liquidia.com) which now employs 37 people in RTP and has raised $25 million in venture financing. DeSimone's laboratory and the PRINT technology recently became a foundation for the new $25 million Carolina Center for Cancer Nanotechnology Excellence funded by the National Cancer Institute. DeSimone is the co-PI of this newly established Center along with Dr. Rudy Juliano. DeSimone received his BS in Chemistry in 1986 from Ursinus College in Collegeville, PA and his Ph.D. in Chemistry in 1990 from Virginia Tech.
		Paolo Decuzzi Associate Professor University of Texas Health Science Center Houston University of Magna Graecia - Italy Dr. Paolo Decuzzi received his Doctoral Degree in Mechanical Engineering at the University of Naples - Italy in 2001. He has been a visiting scientist in several EU and US Universities, including the Dept. of Theoretical and Applied Mechanics of the University of Michigan where he spent half of his 3-year PhD course collaborating with Dr. J. Barber (1999-2000); at the Dept. of Mechanical Engineering of the University of Southampton - UK in collaboration with Dr. Wood (2001); at the Princeton Material Institute collaborating with Dr. D. Srolovitz (2003); and at the M. Doris Davis Heart and Lung Research Institute of the Ohio State University collaborating with Dr. Ferrari (2004). Current research projects include: the development of nanoparticles for the intravascular delivery of therapeutics and in-vivo biomedical imaging; the development of microfludic devices for the in-vitro and ex-vivo analysis of fluid mechanics and biophysical events; the development of nanocantilever beams and nano-porous particles for gas detection and biochemical analysis of fluids. The main fields of application are biomedical, particularly oncology and cardiovascular disease, as well as biochemical warfare agents detection, industrial quality and process control. Research interests include also: the study of adhesion and friction at the micro/nano scale; the optimal design of RF-MEMS switches; the multiscale modeling of non-continuos and non-homogeneous solids; fracture and failure mechanics; transport and diffusion within the microcirculation; the analysis of the specific and non-specific interactions at bio-artificial interfaces (bioadhesion). Dr. Decuzzi has published more than 70 papers in peer-reviewed international journals and conferences. He is associate editor for the international journals Biomedical Microdevices and Journal of the Serbian Society of Computational Mechanics. He has 3 patents currently under review by the USPTO. His research activity on "Geometry in Drug Delivery and Biomedical Imaging" is currently supported by the The Defense Advanced Research Projects Agency (DARPA) in USA and on "Friction and Adhesion at the Nano Scale" by the Eurocores Programs in EU.
		Martin Ostoja-Starzewski Professor of Mechanical Science and Engineering University of Illinois at Urbana-Champaign. Martin Ostoja-Starzewski did his undergraduate studies (1977) at the Cracow University of Technology, Poland, followed by Master's (1980) and Ph.D. (1983) degrees at McGill University, Canada, all in mechanical engineering. He is now Professor of Mechanical Science and Engineering at the University of Illinois at Urbana-Champaign. His research interests are primarily in thermo-mechanics of random and fractal media, hyperbolic thermoelasticity, stochastic methods, and mechanics of head trauma. He wrote 120 journal papers and two books: 1. Microstructural Randomness and Scaling in Mechanics of Materials, CRC (2008); 2. Thermoelasticity with Finite Wave Speeds (with J. Ignaczak), Oxford Mathematical Monographs, OUP (2009). He is co-editor of the CRC Modern Mechanics and Mathematics Series, as well as a member of editorial boards of Journal of Thermal Stresses, Probabilistic Engineering Mechanics, Actual Problems of Aviation and Aerospace Systems, ASME Journal of Applied Mechanics, International Journal of Damage Mechanics, Archive of Applied Mechanics, and Acta Mechanica. He is Fellow of ASME, American Academy of Mechanics, WIF and Associate Fellow of AIAA.
		Dr. Thomas Thundat Corporate Fellow and Leader, Nanoscale Science and Devices Group Oak Ridge National Laboratory. Professor, University of Tennessee, Knoxville University of Burgundy, France Dr. Thomas Thundat is a Corporate Fellow and the leader of the Nanoscale Science and Devices Group at the Oak Ridge National Laboratory. He is also a research professor at the University of Tennessee, Knoxville, and a visiting professor at the University of Burgundy, France. He received his Ph.D in physics from State University of New York at Albany in 1987. He is the author of over 245 publications in refereed journals, 45 book chapters, and 29 patents. Dr. Thundat is the recipient of many awards that include the U.S. Department of Energy's Young Scientist Award, R&D 100 Awards, ASME Pioneer Award, Discover Magazine Award, FLC Awards, Scientific American 50 Award, Jesse Beams Award, Nano 50 Award, Battelle Distinguished Inventor, ORNL and UT-Battelle Awards for invention, publication, and Research and Development. Dr. Thundat is an elected Fellow of the APS, the ECS, and the AAAS. Dr. Thundat's research is currently focused on novel physical, chemical, and biological detection using micro and nano mechanical sensors. His expertise includes physics and chemistry of interfaces, solid-liquid interface, biophysics, scanning probes, nanoscale phenomena, and quantum confined atoms.
		Jennifer West Isabel C. Cameron Professor of Bioengineering; Professor of Chemical and Biomolecular Engineering; Chair of the Department of Bioengineering Rice University Dr. Jennifer West is the Isabel C. Cameron Professor of Bioengineering, professor of chemical and biomolecular engineering and chair of the Department of Bioengineering at Rice University. In the field of tissue engineering, Dr. West's research involves the development of bioengineered arteries that can be used to combat heart disease and problems that arise after angioplasty, the balloon procedure used to open clogged arteries. Dr. West has developed biodegradable scaffolding materials on which genetically engineered cells can grow. Additionally, she's developing polymer materials that can be coated on the arteries and that release nitric oxide, a key chemical that reduces clotting and assists in the healing process. Another area of her work involves biomedical applications of nanoshells, ultrasmall metallic spheres that are engineered with special optical properties. Dr. West, in collaboration with nanoshell creator Naomi Halas, is exploring several biomedical applications for nanoshells, including cancer therapy, drug delivery and medical testing. West received a B.S. in chemical engineering from Massachusetts Institute of Technology, and M.S. and Ph.D. degrees in biomedical engineering at the University of Texas at Austin.
		Chun Li, Ph.D. Professor, Department of Experimental Diagnostic Imaging The University of Texas M. D. Anderson Cancer Center Chun Li, Ph.D. is a professor in the Department of Experimental Diagnostic Imaging at The University of Texas M. D. Anderson Cancer Center. Research in Dr. Li's laboratory is primarily focused on two areas: 1) the development of targeted imaging probes for noninvasive characterization of molecular events associated with tumor progression and regression and 2) the development of novel drug-delivery systems for selective delivery of diagnostic and therapeutic agents. Dr. Li, who earned his doctorate in chemistry at Rutgers-The State University of New Jersey and his undergraduate degree from Peking University in Beijing, has more than 70 papers published in peer-reviewed journals and 24 patents. A polymer-drug conjugate (PG-TXL) originated from his laboratory has advanced into clinical phase III trials studies.