2006 - 2007 Nanobiotechnology Seminar Series
Seminar & Discussion 4:30 - 5:30 pm
Reception 5:30 - 6:00 pm
September 6, 2006
Director, NCI SBIR & STTR Program
NCI SBIR & STTR Bay Area Forum
October 17, 2006
Professor, Material Science & Engineering
Emerging Techniques for Active Biointerfaces
The integration between inorganic, synthetic structures and biological systems is a challenging and evolving process that may lead to new insights into biological behavior, clinical diagnostics and therapeutic treatments. The key problem comes down to one of translation: how do we convert biological stimuli into electronic signals and vice versa? Much of the work in the field has focused on biosensors, yet equally interesting is regulating dynamic biological processes using electrical signals. In this talk I will explore three approaches my group is developing to provide active interfaces between electronics and biological systems. In one case, we will examine how the ionic double layer near a charged electrode surface can regulate the activity of ion-sensitive proteins, providing electronic control of proteins even without redox activity. Within this scheme, the polymerization of the cytoskeletal protein actin is controlled with applied electronic fields. In another example, we show a nanoreservoir chip that can release various chemical species upon electrical stimulation, effectively converting an electrical pulse into a specific biochemical signal. Future platforms to provide direct electronic communication with the interior of a cell will be discussed.
November 21, 2006
Prof., Matls Sci & Eng
and of Electrical Engineering
Director, Stanford Center for Magnetic Nanotechnology
Magnetic Nanoparticles and Biochips for Cancer Diagnostics
Magnetic nanotechnology is finding wide applications in medicine, most notably in magnetic resonance imaging and magnetic separation. However, even more exciting applications of nanotechnology in fighting cancer, heart diseases, and infectious diseases are emerging. We are developing a sensitive and quantitative molecular detection system which is based on magnetic nanoparticles (nanotags) and magneto-nano sensor arrays. The magnetic biochips can be used for rapid and portable DNA detection, pathogen detection, and proteomics.
In this seminar I will first give an introduction to conventional and novel magnetic nanoparticles and magneto-nano biosensors. Then, I will give an in-depth discussion of magneto-nano DNA and protein chips which holds great promises in the early detection and therapy monitoring of cancer and other diseases. In particular, we have designed and fabricated several types of such magnetic biochips (MagArray) consisting of arrays of spin valve detectors with appropriate dimensions, surface chemistry, and microfluidics. An ASIC circuit with a footprint of 2 mm by 2 mm and including row and column addressing decoders and parallel fast readout schemes have been designed and fabricated. The MagArray chips feature redundant and high density of sensors, with a sensor density as high as 0.1 million sensors per squared cm. An advanced electronic test station has been set up as a demonstration vehicle for the integrated evaluation of our magnetic biochips with the custom magnetic nanotags and DNA-based biochemistry. The system is capable of detecting down to 1-30 nanotags.
Real-time detection of DNA signatures and protein targets in buffer and serum samples has been successfully performed in laboratories, suggesting that magnetic biochips hold unparalleled capabilities as compared to competing biochip technologies. We are addressing practical issues in order for magnetic nanotags and biochips to emerge as a killer application in cancer diagnostics. Other biological applications of magnetic nanotechnology will be discussed if time permits.
This work is supported in part by US Navy/DARPA and National Cancer Institute.
November 21, 2006
Associate Professor, Radiation Oncology
Nano-technology for Radiation Oncology Applications
Radiotherapy is one of the major clinical modalities for cancer management. The success of radiation therapy depends on many factors, such as fundamental understanding of radiobiology, accuracy of dose calculation, delivery and measurement, imaging and image guidance. Advancements in nanotechnology afford novel opportunities to improve the current radiation oncology practice. In this talk I will first give a brief introduction on radiotherapy and image-guided radiation therapy. I will then present some initial data in investigating the feasibility of using SWNT field effect transistor (SWNT-FET) for radiation dosimetry applications. Nanoparticles for image enhancement and facilitation of image-guided intervention will also be discussed.
January 23, 2007
Associate Professor, Chemistry and Engineering
Department of Chemistry
Monodisperse Magnetic Nanoparticles for Tumor Cell Targeting
I will summarize our recent efforts in the synthesis and functionalization of monodisperse magnetic nanoparticles for potential cancer diagnostics and therapy. We have developed various synthetic procedures for making monodisperse magnetic nanoparticles of iron oxide MFe2O4 (M = Fe, Co, Mn), core/shell structured M/Fe3O4 (M = Co, Fe), and dumbbell-like NM-Fe3O4 (NM = Au, Pt) with tunable sizes and magnetics. The particles coated with polyethylene glycol and various peptides are stable in physiological conditions and are able to target either cancer cell membranes or cell nuclei depending on their surface functionalization. We hope these nanoparticles can be used as sensitive labels for cancer diagnostics and as efficient delivery tools for therapeutic applications.
February 20, 2007
Professor & Chair, Department of Materials Science & Engineering
Recent Developments in Nano-Characterization
There have been remarkable advances in recent years in the capabilities of instrumentation for the characterization of nano-materials. Scanning electron microscopy approaches 1nm resolution with its great depth of field and now has routine crystallographic methodologies. The focused ion beam machine can use ions or electrons for image formation, and can utilize the former for fashioning materials, sectioning through devices or depositing metals or insulators to make miniature structures. Aberration-corrected transmission electron microscopes have sub-0.1nm resolution both for imaging and probe formation, and can provide chemical mapping at a 1nm level using characteristic energy-loss electrons. Even the surface analytical techniques, once thought to be broad-beam analytical tools, have impressive spatial resolutions, such as 50nm for secondary ion mass spectrometry, 10nm for Auger spectroscopy and sub-10 microns for X-ray photo-electron spectroscopy. This presentation discusses these recent advances, with particular application for nano-technology research, especially for nano-particles and nano-wires. Recent instrument additions to the Stanford Nanocharacterization Laboratory will be discussed.
March 20, 2007
Professor, Biopharmaceutical Sciences
New Materials for Drug Delivery−Lipids & Linkers & Bow−ties
Advances in chemistry and biotechnology enable the synthesis of new materials for drug and gene delivery. The goal is to use these materials to assemble a targeted carrier that can direct drugs after intravenous administration to: specific sites in the body, respond to a signal at the target site and report on the location of delivery. Our group is synthesizing lipids, polymers, linkers and proteins and using them to assemble drug delivery systems. The challenge is to combine the various elements in a robust and economical manner. We have devised new polymers and lipids that enable a number of these functions. In collaboration with Professor Jean Frechet & group at UC Berkeley, we have investigated the role of polymer MW and architecture in controlling their distribution and elimination in mice. Dendritic polymers optimized for distribution into tumors have been used to deliver doxorubicin to treat a murine colon cancer; the polymeric drugs are as effective as doxorubicin delivered in a sterically stabilized liposome. I'll discuss our strategy to further improve drug therapy using drug carriers prepared from other new materials.
- Huang Z, Park JI, Watson DS, Hwang P, Szoka FC Jr. Facile Synthesis of Multivalent Nitrilotriacetic Acid (NTA) and NTA Conjugates for Analytical and Drug Delivery Applications. Bioconjug Chem. 17(6):1592-1600, 2006.
- Lee CC, Gillies ER, Fox ME, Guillaudeu SJ, Frechet JM, Dy EE, Szoka FC. A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas. Proc Natl Acad Sci U S A. 103(45):16649-54, 2006.
April 17, 2007
Professor, Chemistry, Materials Science & Engineering and
Univ of Washington
Putting Nanostructures to Work for Biomedical Research
Complex nanostructures with novel properties can often be prepared using very simple chemical reactions. For instance, galvanic replacement reaction between silver nanocubes and HAuCl4 in an aqueous solution transforms 10−200 nm silver nanocubes into gold nanoboxes and nanocages (nanoboxes with porous walls). By controlling the molar ratio of silver to HAuCl4, the plasmon peaks of resultant nanostructures can be continuously tuned from the blue (400 nm) to the near infrared (1200 nm). These hollow gold nanostructures are characterized by extraordinarily large cross−sections for both absorption and scattering. Optical measurements indicate that the 35−nm gold nanocage has a scattering cross−section of ~0.8x10−15 m2 and an absorption cross−section of ~7.3x10−15 m2; both of them are more than five orders of magnitude larger than those of conventional organic dyes. Exposure of gold nanocages to a camera flash resulted in the instant melting and conversion of gold nanocages into spherical particles due to photothermal heating. Gold nanocages can be easily bioconjugated with antibodies to target any specific cancer cells. This novel class of hollow nanostructures is being developed as both a contrast agent for optical imaging in early−stage detection of cancer and a therapeutic agent for photothermal treatment of cancer, and as nanoscale capsules for targeted drug delivery.
May 15, 2007
Professor, Physics & Division of Bioengineering
Micro and Nanofabricated Interfaces for Therapeutic Delivery
In vivo cellular and drug delivery strategies are being developed that capitalize on the strengths of micro- and nanofabrication. By taking advantage of our ability to control chemistry and topography at submicron size scales, we can design synthetic devices which modulate cell function. Examples include nanoporous capsules for cellular delivery, microfabricated drug delivery devices to penetrate cellular barriers, and drug-eluting microrods to control tissue regeneration. Such engineered interfaces may be optimized for biomolecular selectivity and surface bioactivity. Micro- and nanotechnology can add flexibility to current delivery practices while becoming an enabling technology leading not only to new laboratory techniques, but also to new platforms for delivering therapy to the patient.
June 19, 2007
Camille and Henry Dreyfus Professor of Chemistry
Imaging model membranes beyond the diffraction limit
Our lab has developed a wide range of methods for patterning lipid bilayers on solid supports. The planar geometry of supported bilayer systems is ideal for high resolution imaging methods. The lateral composition of membranes can be analyzed by high spatial resolution secondary ion mass spectrometry. Results will be described for simple membrane compositions and phase separated domains suggesting the potential of this method for the analysis of membrane organization in complex membranes.
July 17, 2007
Associate Lab Director, Physical Science
Director, Material Science Division
Nanocrystals and Nanocrystal Molecules as Single Molecule Optical Probes in Biomedical Imaging
This talk will describe the use of colloidal inorganic semiconductor and metallic nanocrystals as single molecule probes in biomedicine. Compared to conventional organic chromophores, the nanocrystals offer advantages with respect to resistance to photobleaching and spectral tuning. Our early work focused on the use of individual nanocrystals, while our more recent work is dedicated to the development of nanocrystal groupings, which can be used as more advanced probes of distance and conformational change.
August 21, 2007
Associate Director,Center for
Probing the Nanoscale
Nanoprobes to Enable Next-Generation Biotechnology
Rapid advancements in nanoprobe technology enable us to visualize, measure and manipulate matter at an unprecedented scale. Nanoprobes can now manipulate individual atoms and routinely image structures one hundred thousand times finer than a human hair. Although these probes have been extensively applied for the metrology of inorganic materials, the specialized demands of imaging biological structures has required the development of novel nanoprobes and techniques.
The Center for Probing the Nanoscale (CPN) is an NSF-funded collaborative effort between Stanford University and IBM that focuses on developing novel tools to map electronic, magnetic, mechanical, and other material properties on the nanometer scale. This seminar will examine some of the current challenges of biological imaging and highlight several CPN research projects that have biological imaging applications, including a magnetic resonance force microscope (MRFM) with better than 100 nm resolution, a near-field scanning microwave microscope and a harmonic force microscope capable of differentiating between single-stranded and double-stranded DNA.
September 18, 2007
Dept of Pharmaceutical Sciences &
Center for Molecular Drug Targeting (CMDT)
Univ of Michigan
Cytosolic delivery of macromolecules using nano-sized drug carriers mimicking Listeria-cell invasion
The enormous potential and full efficacy of many polypeptide- or nucleic acid-based macromolecular therapeutic agents, despite their intrinsic advantages of high potency and low cytotoxicity, can be achieved only when combined with appropriate delivery systems that are tailored for targeting/delivery to the exact relevant sites at cellular and subcellular levels.
Unique targeted cytosolic delivery systems have been developed utilizing the cell-invasion mechanism of an intracellular bacterium, Listeria monocytogenes, to mediate escape from the endocytic compartment into the cytosol of target cells. The cytosol-targeting mechanism of Listeria, primarily mediated by the highly regulated, cholesterol-dependent, pH-dependent pore-forming cytolysin, listeriolysin O (LLO), is incorporated into various delivery platforms such as liposomes or polymeric particles. Delivery of exogenous proteins, oligonucleotides and plasmid DNA using this non-viral, non-bacterial delivery strategy has been investigated and characterized both in cell culture systems and in vivo.
November 20, 2007
UNC, Chapel Hill
Nanotechnology for the Delivery of Therapeutic Nucleic Acids
Antisense and siRNA oligonucleotides are promising tools for precise regulation of gene expression both in the laboratory and in therapeutic contexts. One of the key issues for olignucleotide-based therapeutics is effective delivery to cells and tissues. Our laboratory has explored a variety of delivery strategies, including peptide-oligonucleotide conjugates, complexes or conjugates of oligonucleotides with nanocarriers, and Adeno Associated Viral vectors for siRNA. While each approach has its advantages and disadvantages, we are currently enthused about delivering oligonucleotides by receptor mediated endocytosis via conjugation of the oligonucleotide with high affinity, receptor selective ligands.
December 21, 2007
Department of Materials Science and Engineering
Inorganic nanowires can be made with diameters of 1-100 nm and lengths up to hundreds of micrometer, and with materials ranging from metal, semiconductor and ionic conductors. A unique character of nanowires is that they support charge carrier transport along the length while maintaining a nanoscale dimension across the diameter and a large surface-to-volume ratio. My group has been exploring this character for the development of new energy- and bio- technologies. I will give an example of using nanowires as new generation of Li-ion battery electrodes. Displacement and alloying mechanism has been explored in nanowires to realize battery electrodes with 10 times higher capacity than the existing technology. I will also present two ways to use nanowires as biological sensors. One is based on the concept of chemical field effect transistor with semiconductor nanowires. Highly sensitive and selective biodetection can be realized with nanowire sensors. The other is based to redox reactions on metal nanowires surface. Our results show that nanowire materials can bring new exciting opportunities to energy- and bio- technologies.
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