Eighth Annual NBTC Nanobiotechnology Symposium

Web Sites

Journal of Nanobiotechnology
The Journal of Nanobiotechnology publishes papers on all aspects of scientific and technological advances in the fields of medical, biological and nanoscale sciences.

The Kavli Foundation
Focusing on cosmology, neuroscience, and nanoscience, this organization is developing an international program of research institutes, prizes, symposia promoting increased public understanding of science and support for scientists and their work.

Kavli Institute at Cornell for Nanoscale Science
Fosters a collaborative multli-disciplinary research community of researchers working at the atomic and molecular scale.

National Cancer Institute (NCI)'s Alliance for Nanotechnology in Cancer
An initiative to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.

National Nanotechnology Initiative
The National Nanotechnology Initiative (NNI) is a federal R&D program established to coordinate the multiagency efforts in nanoscale science, engineering, and technology.

NBTC Nanobiotechnology Center
This Cornell University institute is pursuing projects in an emerging area of scientific and technological opportunity that integrates nano/microfabrication and biosystems.

New York State Foundation for Science, Technology and Innovation
NYSTAR works to further high-technology academic research and economic development in New York State.

Articles

Wolfhard Almers

An SJ, Almers W. 2004. Tracking SNARE complex formation in live endocrine cells.Science 306: 1042-1046.

Coggins MR, Grabner CP, Almers W, Zenisek D. 2007. Stimulated exocytosis of endosomes in goldfish retinal bipolar neurons. J. Physiol. 584: 853-865.

Perrais D, Kleppe IC, Taraska JW, Almers W. 2004. Recapture after exocytosis causes differential retention of protein in granules of bovine chromaffin cells. J. Physiol. 560(Pt 2): 413-428. Full Text

Taraska JW, Almers W. 2004. Bilayers merge even when exocytosis is transient. Proc. Natl. Acad. Sci. USA 101: 8780-8785. Full Text

Wan L, Almers W, Chen W. 2005. Two ribeye genes in teleosts: the role of Ribeye in ribbon formation and bipolar cell development. J. Neurosci. 25: 941-949. Full Text

Harold Craighead

Ilic B, Krylov S, Kondratovich M, Craighead HG. 2007. Selective vibrational detachment of microspheres using optically excited in-plane motion of nanomechanical beams. Nano Lett. 7: 2171-2177.

Moran-Mirabal JM, Aubrecht DM, Craighead HG. 2007. Phase separation and fractal domain formation in phospholipid/diacetylene-supported lipid bilayers. Langmuir 23: 10661-10671.

Slinker JD, DeFranco JA, Jaquith MJ, et al. 2007. Direct measurement of the electric-field distribution in a light-emitting electrochemical cell. Nat. Mater. 6: 894-899.

Waggoner PS, Craighead HG. 2007. Micro- and nanomechanical sensors for environmental, chemical, and biological detection. Lab Chip 7: 1238-1255.

Verbridge SS, Shapiro DF, Craighead HG, Parpia JM. 2007. Macroscopic tuning of nanomechanics: substrate bending for reversible control of frequency and quality factor of nanostring resonators. Nano Lett. 7: 1728-1735.

Claudia Fischbach-Teschl

Fischbach C, Chen R, Matsumoto T, et al. 2007. Engineering tumors with 3D scaffolds. Nat. Methods 4: 855-860.

Fischbach C, Mooney DJ. 2007. Polymers for pro- and anti-angiogenic therapy. Biomaterials 28: 2069-2076.

Jack Henion

Ganem B, Henion JD. 2003. Going gently into flight: analyzing noncovalent interactions by mass spectrometry. Bioorg. Med. Chem. 11: 311-314.

Yang Y, Kameoka J, Wachs T, et al. 2004. Quantitative mass spectrometric determination of methylphenidate concentration in urine using an electrospray ionization source integrated with a polymer microchip. Anal. Chem. 76: 2568-2574.

Zhang S, Van Pelt CK, Henion JD. 2003. Automated chip-based nanoelectrospray-mass spectrometry for rapid identification of proteins separated by two-dimensional gel electrophoresis. Electrophoresis 24: 3620-3632.

Kimberly Jones

Abitoye J, Mukherjee P, Jones K. 2005. Ion implantation: effect on flux and rejection properties of NF membranes. Environ. Sci. Technol. 39: 6487-6493.

Jones K, Leevy J, LaHee S. 2004. High-flux, low-fouling membrane system for wastewater recycle in space missions. SAE 2004-01-2464.

Jones K, O'Melia C. 2001. Ultrafiltration of protein and humic substances: Effect of solution chemistry on fouling and flux decline. J. Memb. Sci. 193: 163-173.

Jones K, O'Melia C. 2000. Protein and humic acid adsorption onto hydrophilic membrane surfaces: effects of pH and ionic strength. J. Memb. Sci. 165: 30-46.

Mukherjee P, Jones K, Abitoye J. 2005. Surface modification of nanofiltration membranes by ion implantation. J. Memb. Sci. 254: 303-310.

Philip Leopold

De BP, Heguy A, Hackett NR, et al. 2006. High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. Mol. Ther. 13: 67-76.

Kelkar S, De BP, Gao G, et al. 2006. A common mechanism for cytoplasmic dynein-dependent microtubule binding shared among adeno-associated virus and adenovirus serotypes. J. Virol. 80: 7781-7785. Full Text

Leopold PL, Crystal RG. 2007. Intracellular trafficking of adenovirus: many means to many ends. Adv. Drug Deliv. Rev. 59: 810-821.

Leopold PL, Wendland RL, Vincent T, Crystal RG. 2006. Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway. J. Virol. 80: 10237-10247. Full Text

Leopold PL, Pfister KK. 2006. Viral strategies for intracellular trafficking: motors and microtubules. Traffic 7: 516-523.

Pergolizzi RG, Jin G, Chan D, et al. 2006. Correction of a murine model of von Willebrand disease by gene transfer. Blood 108: 862-869. Full Text

Manfred Lindau

Dernick G, Gong LW, Tabares L, et al. 2005. Patch amperometry: high-resolution measurements of single-vesicle fusion and release. Nat. Methods 2: 699-708.

Gong LW, de Toledo GA, Lindau M. 2007. Exocytotic catecholamine release is not associated with cation flux through channels in the vesicle membrane but Na+ influx through the fusion pore. Nat Cell Biol. 9: 915-922.

Gong LW, Di Paolo G, Diaz E, et al. 2005. Phosphatidylinositol phosphate kinase type I gamma regulates dynamics of large dense-core vesicle fusion. Proc. Natl. Acad. Sci. USA 102: 5204-5209. Full Text

Gong LW, Hafez I, Alvarez de Toledo G, Lindau M. 2003. Secretory vesicles membrane area is regulated in tandem with quantal size in chromaffin cells. J. Neurosci. 23: 7917-7921. Full Text

Hafez I, Kisler K, Berberian K, et al. 2005. Electrochemical imaging of fusion pore openings by electrochemical detector arrays. Proc. Natl. Acad. Sci. USA 102: 13879-13884. Full Text

Dan Luo

Li Y, Cu YT, Luo D. 2005. Multiplexed detection of pathogen DNA with DNA-based fluorescence nanobarcodes. Nat. Biotechnol. 23: 885-889.

Luo D, Li Y, Um SH, Cu Y. 2006. A dendrimer-like DNA-based vector for DNA delivery: a viral and nonviral hybrid approach. Methods Mol. Med. 127: 115-125.

Um SH, Lee JB, Kwon SY, et al. 2006. Dendrimer-like DNA-based fluorescence nanobarcodes. Nat. Protoc. 1: 995-1000.

Um SH, Lee JB, Park N, et al. 2006. Enzyme-catalysed assembly of DNA hydrogel. Nat. Mater. 5: 707-801.

Brian MacCraith

Burke CS, McGaughey O, Sabattié JM, et al. 2005. Development of an integrated optic oxygen sensor using a novel, generic platform. Analyst 130: 41-45.

Duffy CF, MacCraith B, Diamond D, et al. 2006. Fast electrophoretic analysis of individual mitochondria using microchip capillary electrophoresis with laser induced fluorescence detection. Lab Chip 6: 1007-1011.

Holthoff WG, Tehan EC, Bukowski RM, et al. 2005. Radioluminescent light source for the development of optical sensor arrays. Anal. Chem. 77: 718-723.

Laib S, MacCraith BD. 2007. Immobilization of biomolecules on cycloolefin polymer supports. Anal. Chem. 79: 6264-6270.

Tweedie M, Subramanian R, Lemoine P, et al. 2006. Fabrication of impedimetric sensors for label-free Point-of-Care immunoassay cardiac marker systems, with passive microfluidic delivery. Conf. Proc. IEEE Eng. Med. Biol. Soc. 1: 4610-4614.

Tyrrell E, Gibson C, MacCraith BD, et al. 2004. Development of a micro-fluidic manifold for copper monitoring utilising chemiluminescence detection. Lab Chip 4: 384-390.

Yosi Shacham-Diamand

Popovtzer R, Neufeld T, Biran D, et al. 2005. Novel integrated electrochemical nano-biochip for toxicity detection in water. Nano Lett. 5: 1023-1027.

Abraham Stroock

Badaire S, Cottin-Bizonne C, Woody JW, et al. 2007. Shape selectivity in the assembly of lithographically designed colloidal particles. J. Am. Chem. Soc. 129: 40-41.

Cabodi M, Cross VL, Qu Z, et al. 2007. An active wound dressing for controlled convective mass transfer with the wound bed. J. Biomed. Mater. Res. B Appl. Biomater. 82: 210-222.

Choi NW, Cabodi M, Held B, et al. 2007. Microfluidic scaffolds for tissue engineering. Nat. Mater. 6: 908-915.

Gleghorn JP, Lee CS, Cabodi M, et al. 2007. Adhesive properties of laminated alginate gels for tissue engineering of layered structures. J. Biomed. Mater. Res. A Sep 5; [Epub ahead of print]

Kane RS, Stroock AD. 2007. Nanobiotechnology: protein-nanomaterial interactions. Biotechnol. Prog. 23: 316-319.

Lee CS, Gleghorn JP, Won Choi N, et al. 2007. Integration of layered chondrocyte-seeded alginate hydrogel scaffolds. Biomaterials 28: 2987-2993.

Larry Walker

Jeoh T, Wilson DB, Walker LP. 2006. Effect of cellulase mole fraction and cellulose recalcitrance on synergism in cellulose hydrolysis and binding. Biotechnol. Prog. 22: 270-277.

Watt Webb

Baumgart T, Hammond AT, Sengupta P, et al. 2007. Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles. Proc. Natl. Acad. Sci. USA 104: 3165-3170. Full Text

Chen H, Rhoades E, Butler JS, et al. 2007. Dynamics of equilibrium structural fluctuations of apomyoglobin measured by fluorescence correlation spectroscopy. Proc. Natl. Acad. Sci. USA 104: 10459-10464. Full Text

Díaz-Ríos M, Dombeck DA, Webb WW, Harris-Warrick RM. 2007. Serotonin modulates dendritic calcium influx in commissural interneurons in the mouse spinal locomotor network. J. Neurophysiol. 98: 2157-2167.

Fecko CJ, Munson KM, Saunders A, et al. 2007. Comparison of femtosecond laser and continuous wave UV sources for protein-nucleic acid crosslinking. Photochem. Photobiol. 83: 1394-1404.

Ouzounov DG, Moll KD, Foster MA, et al. 2002. Delivery of nanojoule femtosecond pulses through large-core microstructured fibers. Opt. Lett. 27: 1513-1515.

Ni Z, Saunders A, Fuda NJ, et al. 2007. P-TEFb is critical for the maturation of RNA Polymerase II into productive elongation in vivo. Mol. Cell Biol. Dec 10; [Epub ahead of print]

On October 1, 2007, scientists from Cornell University and the New York State Office of Science, Technology, and Innovation (NYSTAR) were joined by speakers from around the globe to discuss their research at the Eighth Annual Nanobiotechnology Symposium, organized by and held at Cornell's Nanobiotechnology Center (NBTC). The annual event is part of the Center's efforts aimed at "disseminating knowledge regarding [its] discoveries and ...enhancing the economic impact and commercialization of nanobiotechnology," said Robert Buhrman, Cornell's newly appointed Vice Provost for Research. The symposium was cosponsored by the NBTC, the Kavli Institute at Cornell, and the New York Academy of Sciences.

NBTC Director Harold Craighead noted in his welcoming remarks that in each of the eight years the symposium has been held, the program has changed in character, becoming increasingly outward looking with time. The themes for this year's event were:

• Improving medical imaging, diagnostics, and therapeutics
• Nanobiotechnology research and economic development
• Directions for sustainable energy

A hallmark of the Center has always been an effective integration of scientists—chemists, engineers, and physical and life scientists pursuing the relatively new area of nanobiotechnology. So it was not surprising that terms like collaboration, teamwork, interaction, interdisciplinary, and building bridges were heard repeatedly throughout the daylong symposium and were a common thread that wove many of the various presentations together.

Nanomedicine

A number of speakers shared their research discoveries in the rapidly developing field of nanomedicine. Nanomedicine utilizes engineered nanodevices and nanostructures in both the treatment and prevention of disease at the molecular level.

Abraham Stroock (Cornell), described a wound dressing with microfluidic properties that has all the characteristics of conventional dressings, but also has input (among these a mechanism for drug delivery) and output controls to tailor the environment and monitor the biochemical condition of the wound bed. The wound dressing was just one example of what Stroock calls "functional microphysiological structures that interface with biology." He listed some others as:

• prosthetics
• scaffolds for tissue engineering
• model tissues for basic biology, pharmokinetics, and toxicology

Another example of a novel approach to facilitating drug delivery through nanobiotechnology came from Philip Leopold (Weill Cornell Medical College) who relayed to the audience how viruses can be used as mentors or vehicles for this purpose. Comparing a virus with the space shuttle, Leopold said, "They both have three stages, get where they're going in just a few minutes, and deliver their payloads with an expectation of 100% efficiency." However, viruses are not ideal vectors for gene delivery, in part because they provoke an immune response.

Leopold discussed a systematic way of thinking about the tools that viruses use for gene delivery. He noted that a virus uses cellular proteins to help it deliver its genome to the nucleus, carrying out what he calls "subcellular mimicry." In this process, the virus tricks the cell into thinking it is carrying out a normal function, such as nutrient uptake or organelle motility. From this observation, Leopold hypothesizes that we should be able to create an efficient nonviral vector with human proteins that can carry out those viral functions, exploiting normal cellular processes in the same manner. "Making an efficient nonviral gene transfer shouldn't be rocket science," he said in his concluding remarks. "It's just nanotechnology!"

Brian MacCraith (Dublin City University, Ireland) explained how fluorescence-based biochips could be used in revolutionary diagnostic devices for home use that provide early warning of life-threatening diseases, control of chronic diseases, and monitoring of well being. One such device—a myocardial infarction early warning system, if you will—that's based on the glucose testing paradigm, would track changes related to diet and general health to provide information as to whether or not an individual is at risk for future cardiac problems.

For this type of system to become a commonly used diagnostic, a number of hurdles have to be overcome. MacCraith described one of the challenges, that of optimizing fluorescence-based biochips so that the signal-to-noise ratio is higher, the signal is amplified, and detection of impending disease can occur before the condition becomes a problem. His work showed that one reason the sensitivity of these fluorescence-based chips is low is that most of the light hitting the chip gets trapped inside, and only a small fraction is emitted out of the bottom or above the chip, where can be detected by the optics system. By finding ways to get around this problem, the team was able to greatly enhance the biochip's sensitivity. MacCraith's group is working on other complementary approaches, including the development of advanced diagnostic biochips based on plasmon-enhanced fluorescence.

Nanotechnology can also be used in cell biological studies to mimic the complicated microenvironment in which cells function in the body. All cells interact with the extracellular matrix (ECM) via integrins, which are the cell surface receptors that mediate various intracellular signals to control migration, proliferation, and differentiation. However, said Claudia Fischbach-Teschl (Cornell), what is not very well understood is how these interactions contribute to another phenomenon—tumor vascularization, or the stimulation of new blood vessel growth by signaling from tumor cells. Tumor vascularization is a critical step both for tumor growth and for tumor cells to metastasize to distant organs.

Studies of cell-ECM interactions are usually conducted with two-dimensional culture systems in which petri dishes are coated with ECM components. But these systems are a poor substitute for the actual microenvironment of a tumor. Fischbach-Teschl is working on building polymeric systems to study the role of three-dimensional cell-ECM interactions in tumor vascularization. In one early indication that the structure of the culture matters, she has found that levels of growth factor secretion from tumor cells differ depending on whether the study is conducted in a two-dimensional or three-dimensional culture system.

Yosi Shacham-Diamand (Tel Aviv University) described whole cell bio-chips in which optical and electrochemical detection systems interface with living cells. The cells act as sensors while the electronic components provide a simple and sensitive way to report the output. Such systems have a number of potential applications, including acute toxicant detection in drinking water, screening drugs for activity or toxicity, diagnostic clinical information, basic neuroscience, and environmental engineering. Shacham-Diamand pointed out that using live cells in this manner is a modern day twist on the use of caged live canaries by Welsh coal miners to detect toxic fumes. "This is why sometimes our students call it the 'Canary Project,'" he said.

Nanobiotechnology and entrepreneurship

Steve Kresovich, Vice Provost for Life Sciences at Cornell, in his remarks introducing the afternoon program, reminded the audience that linking research with economic development and building bridges between the two is of the highest priority. "We see in the future closer collaborations, with research coming out of the University as an economic driver," Kresovich said.

"The new economy strategy talks about entrepreneurial activities and the importance of innovation in any firm regardless of its size," said Ed Reinfurt, acting executive director of NYSTAR. "If you can't embrace innovation, if you're not doing something better and different from your competitor, you're not going to succeed."

He continued, saying that New York State policy makers ask themselves four main questions when making policy decisions about research, innovation, and the economy: Where is New York today? Where does it need to go? How do we get the greatest impact from our investments? And how do we best position New York to thrive in a global innovation economy? "We need innovation to be the leader in economic development," he said.

Back row from left: Claudia Fischbach-Teschl, Brian MacCraith, Philip Leopold, Wolfhard Almers, Manfred Lindau, Larry Walker.
Front row from left: Watt W. Webb, Kimberly L. Jones, Dan Luo.

Universities are key, according to Reinfurt, to New York State continuing to thrive and to increase productivity and innovation since universities offer strong leadership, they support promising scientists and engineers, and, in partnership with the State, they can invest in research and innovation that is aligned with important industry clusters.

Advion is a good example of the kinds of partnerships to which Reinfurt was referring. Jack Henion, Advion's cofounder, chairman, chief scientific officer, and former Cornell University faculty member, started the company as a service business doing liquid chromatography/mass spectrometry analysis for the pharmaceutical industry. The company developed other services according to need from industry, such as sample management, metabolic identification, pharmacokinetic, and immunoassay services.

In the late 1990s, Advion became Advion Biosystems, a product business based on Henion's lab's work at Cornell, which used polymer-based chips to combine analytic chemistry with mass spectrometry. These chips have application to the pharmaceutical industry, which needed to analyze millions of samples quickly. New possibilities include combining data from the chips with PET and the new micro-PET technology for cancer diagnosis. "The key is an infrastructure and people that know what to do, a culture that fosters creativity," Henion said.

Other new biotechnologies

Dan Luo (Cornell) elicited a chuckle from the audience when he called NBTC one of the world's three most important inventions, the other two being polymers and DNA.

Luo uses DNA as a nanoscale material not only to do basic studies, but for applications in nanotechnology, medicine, materials science, and engineering. "We use DNA to construct nanoscale architecture," Luo said. "In other words we want to do DNA Lego or Tinkertoys." Luo's group has created DNA dendrimers, DNA-addressable molecules and materials, DNA-based barcode systems, DNA hydrogels, DNA liposomes, DNA-Au hybrid nanoparticles, and a DNA gel that can produce a large quantity of proteins without any living organisms.

Nanoscale technologies can be used to build new materials, and could play a role in environmental sustainability.

With the aforementioned DNA barcode they were able to detect anthrax bacteria, ebola virus, and SARS virus simultaneously. Using a form of the DNA encapsulated hydrogel, insulin was delivered to the cells of patients to treat type 1 diabetes. The latter was done in collaboration with researchers at Cornell Weill Medical Center.

Luo says that he and his partners have taken the first steps toward commercialization forming a company called DNANO. The group has received a $500,000 NYSTAR technology transfer award to support the barcode technology.

Concerns about energy costs and availability, and more recently issues of climate change, greenhouse gas emissions, national security, and global competition, have spurred the promotion of biofuels as one component of the nation's renewable energy portfolio. "Success in meeting the objective of developing 'green' industrial processes that are cost effective and sustainable requires coupling the core basic sciences with advanced materials, separation processes and, yes, nanobiotechnology to develop the next generation of bioconversion processes and systems," said Cornell's Larry Walker. "An emphasis on industrial biotechnology links us with nanobiotechnology, which in turn links us to biofuels."

A reception and lively poster session with more than 60 posters allowed meeting participants to probe the day's topics in more detail and exchange ideas about future collaborations.