NYU-Poly
NYU Dental School
NYU Medical School
NYU-Poly
Whispering Gallery Mode Bio-sensing
The Whispering Gallery Mode Bio-sensor (WGM-B) is the optical analog of a tuning fork. Dust falling on a tuning fork lowers its tone. Not only does this frequency shift detect the binding event, but its magnitude also enables the mass of the dust to be determined. “Particular dust” would be detected by adding appropriate “antibodies” to the surface. Unlike the mechanical tuning fork, a WGM-B utilizes a laser driven microsphere that operates at an optical frequency 12 orders of magnitude higher and with little leakage of energy. This improves sensitivity- instead of being sensitive to 10 micro-grams, it can sense 10 nano-nanograms, less that the mass of an HIV or InfluenzaA virion. In addition the WGM-B is ideally suited for interaction measurements since the resonance shift directly measures the height of the antigen above the surface with nanoscopic precision, while temporal fluctuations in this shift quantitatively reveal interfacial forces. These features make the WGM-B a quantitative probe of interfacial interactions, and a research area that relies heavily on understanding these interactions.
Electroactive surfaces
Surface directed assembly of functional molecules creates opportunities for precision, confinement and enhanced binding both with ligands on device surfaces or with receptors on biological entities.
Kalle Levon's expertise on polyelectrolytes and organic electronics gives the initial pier reaching out to the vast ocean of health sciences. The three approaches on synthetic antibodies, potentiometric diagnostics and high entropy surfaces with modern electrochemical tools for nanosize control drive the innovations in the research, with the following examples:
- Interface control for diagnostics
- Surface imprinting for antibody mimics for early detection of cancer biomarkers
- Ion channel/bilayer as ionophores on Ion Selective Electrodes (ISE)
- Ion sensitive electrodes for monitoring antibody-antigen binding
- Floating gate surface for selective field effect transistor.
- Interfacial control of cell differentiation,
- Stem cells on charged controlled surfaces of electrospun nano-fibers
- Electroactive nanogels for surface modification and controlled release.
The research activity entails an annual meeting, the first Saturday in December, and for 15 years, international specialists in organic electronics have gathered at Poly: http://seam.poly.edu
The design of smart biomaterials capable of self-assembly is critical for producing advanced materials. The ultimate goal of research in the Montclare lab is to design and synthesize self-assembling artificial biomacromolecules capable of selectively and efficiently interacting with cells and tissue. Inspired by natural self-assembling proteins, the lab has synthesized and characterized block polymers comprised of the b-spiral elastin (E) and a-helical COMPcc (C) domains. These two protein motifs have been selected because they not only differ in structure but also bear distinct modes of self-assembly. The Montclare group have demonstrated that the overall micro- and macrostructures of the block polymers including the temperature and small molecule dependence are dictated by the orientation of the fusions as well as the number of repeated blocks, in stark contrast to synthetic block polymers. These protein block polymers demonstrate smart behavior in which an external stimulus can alter the conformation and mode of self-assembly. Moreover, they demonstrated that these polymers can bind small molecules such as vitamin D3 and all-trans retinol—two important molecules involved in signaling events for tissue formation. As a result, these polymers may serve as scaffolds or carriers for small molecule protection and delivery. For the future, the Montclare’s lab plans to combine orthogonal chemical handles as well as infuse additional binding motifs to alter the physical properties of these block polymers. A systematic approach to control the temperature dependence behavior, mechanical stiffness and density of cell binding domains are underway. Overall the long-term goal of the lab is to be abledesign or engineer artificial scaffolds for regenerative medicine.
Whispering Gallery Mode Sensor for Studies of surface molecules
Whispering gallery mode (WGM) sensor utilizes a sharp resonance of photonic modes in a glass microsphere. As molecules adsorb onto the glass surface, the resonance shifts, which can be detected with accuracy. The shift provides information on the size of the molecules, their surface density, and the orientation. Being selectively sensitive to the immediate neighborhood of the surface (< 100 nm), the sensor is a versatile tool to examine the changes that occur on the surface. The WGM sensor may open up a new area of molecular electromagnetism. Having a control over the electromagnetic field on the surface (the amplitude, the phase, and their spatial distributions), we can watch the surface-bound molecules as they undergo conformational changes.
Polysaccharides
Our research focuses on biological macromolecules, with unique expertise in the polysaccharide hyaluronan. We investigate the biophysical chemistry of macromolecules in solution, on surfaces, and in confined or crowded environments. We develop new analytical methods for the analysis of polysaccharide structure and protein binding interactions in biological environments. We are developing models for hyaluronan structure and function in pericellular and extracellular matrices. We apply atomic force microscopy methods for the imaging and physical characterization of single biological macromolecules and nanoparticles on surfaces of defined structure and hydration. Our work has resulted in the discovery and development of new biomaterials and bioactive surface- tethered complexes with medical applications.
Optical techniques and Crystallization
We have recently developed a new technique for characterizing the defect structure of block copolymer thin films. We call this technique guided wave depolarized light scattering (GWDLS). The method is based on the detection of depolarized light scattered from thin films by using the thin film as a planar optical waveguide, and it provides a global, average measure of defect structure in samples, in contrast to techniques such as SEM and AFM that measure local defect structure. By analyzing the intensity and angular spread of the depolarized scattered light, we can determine the size and nature of the grain structure in the film.
Recently, Garetz, Arnold and Ward at NYU have embarked on a collaboration involving the control of polymorph formation in levitated supersaturated microdroplets. In the small volumes of microdroplets, one can achieve much higher supersaturations than in bulk solutions, partly because the nucleation rate is directly proportional to the sample volume. To obtain an observable nucleation rate in a microdroplet, it is necessary to substantially increase the nucleation rate by increasing the supersaturation or by providing surface templates – surfactants – at the air-water interface to accelerate nucleation. These surfactant interfaces, ranging from ionic fatty acids to non-ionic ethoxylated alkanes to mixed surfactant layers, are expected to lower the activation barrier for nucleation and thus accelerate it. By eliminating impurity-induced heterogeneous crystallization through confinement in ultrapure microdroplets, this approach provides a unique opportunity to examine designer interfaces for better control of heterogeneous nucleation.
Self-Assembled Monolayers, Nanoparticles
We synthesize surface active molecules and use them to prepare self-assembled monolayers (SAMs) and mixed SAMs. These molecularly designed systems provide engineered surfaces for wetting studies, surface-initiated polymerization, two-dimensional nucleation and growth, as well as attachment of biomolecules, e.g., enzymes. In addition, our group is preparing different nanoparticles and functionalizes them to serve as drug and gene delivery systems, as well as “magnetic enzymes”.
Recently, we showed that Adenylate Kinase protein preserves its high functionality after being immobilized on a gold surface, using a new, fast, easy, and reliable procedure. The mutated protein was attached to the gold surface via a SAM of 1,6-hexanedithiole. Enzymatic activity tests of the enzyme, attached through S-S bonds to a gold surface, were 100 times higher than what is expected for this amount of protein. Future development of this technology might produce interesting applications of protein-based sensors, and assembly lines, which will mimic processes in nature, for obtaining desirable product with greater yield, lower cost and with no adverse effects on the environment.
Macromolecular Dynamics
This part of the proposed work focuses on the dynamics of ultra-thin, nano-size materials exposed to various external perturbations (electric, magnetic and/or mechanical field).
The knowledge of dynamics is crucial because we learn about molecular motions with vastly different time scales and length scales that govern properties and functions of these materials.
The systems of interest are broadly defined as complex fluids and include both synthetic (copolymers, networks, liquid crystals, gels) and biological molecules (proteins, DNA). Targeted applications include drug encapsulation, enzyme catalysis, molecular electronic circuitry, oil-recovery, high-throughput screening, optical filters, sensors, magneto-optical systems, and so on.
All samples are ultra thin films in the range between ca. 5 and 150 nm. Sample are confined between two solid substrates or deposited on a solid substrate with one free (air) interface. Confinement affects dynamics and the nature of the solid-liquid interface is expected to play an important role in the interactions between the surface and the complex fluid that affect dynamics.
Among available experimental techniques for the study of molecular dynamics, dielectric relaxation spectroscopy (DRS) is rapidly becoming a dominant tool because of its unparalleled frequency range of up to 16 decades. This feature of DRS enables one to capture dynamic events over a remarkably broad range of length scales and time scales, from minutes to picoseconds.
Biomolecular Interactions at Interfaces
The Levicky group is studying biomolecular interactions at interfaces, with emphasis on the physical behavior of biomacromolecules such as nucleic acids and the associated impact on applications, especially in the diagnostic arena. These studies often involve the use of fluorescently-tagged species to monitor the time evolution and extents of bioaffinity surface reactions. Availability of fluorescence-based imaging is essential to these efforts because it is imaging that enables measurements to be carried out in an array format, thus bringing a number of key benefits similar to commercial microarray platforms. From an experimental perspective, array formats allow multiple measurement replicates to be performed under fixed sample conditions so as to provide statistical error
analysis, as well as to carefully test the effect of a deliberately-varied surface variable (e.g. surface chemistry) while keeping solution conditions fixed. From the perspective of applications, array formats enable the parallel monitoring of multiple surface reactions simultaneously, thus allowing highly multiplexed diagnostics.
Molecular Probes
Kim’s lab is focusing on development of a molecular probe for rapid and specific detection of toxic protein aggregates in the Alzheimer’s disease (AD) patient brain. Rapid detection is important since the toxic species can change their shapes, structures, and toxicities over short periods of time. Currently available compounds or methods, however, are inappropriate for rapid and specific detection of toxic species in AD. A peptide probe, which generates detectable signals upon recognition of toxic species in AD, has been developed in Kim’s lab. We are currently applying a protein engineering approach to optimize a peptide probe for improved specificity and sensitivity. A peptide probe will further be tested for in vivo detection of toxic protein aggregates. This approach holds promise for imaging applications leading to patient diagnosis as well as for screening of therapeutic agents that can alter the protein aggregation process and the resulting aggregate toxicity.
The Kim group has also been developing a novel and potentially general method for stabilization of enzymes by domain fusion. The developed method increased kinetic stability of an enzyme by > 6-fold without any compromise in activity. We are currently exploring various ways of domain fusion through rational and combinatorial designs. The method will further be applied to other enzymes to test its generality. This approach will allow functional integration of an enzyme into non-proteinous structures as well as exploration of larger sequence spaces for evolution of proteins into variants with distinct properties.
Liposomes
Lipid rafts or lipid heterogeneities on plasma membranes are associated with critical biological phenomena including cell signaling and viral infection mechanisms. Understanding the biophysical forces among lipids that play a role in these phenomena may potentially impact the control of related cell functions and associated diseases. Sofou’s research has a twofold aim. First, to evaluate the role of intermolecular forces governing the formation of lipid heterogeneities in model membranes, and the significance of these heterogeneities in altering collective membrane properties such as permeability, fusogenicity and local multivalency. Second, to engineer heterogeneous lipid membranes in the form of unilamellar vesicles exhibiting triggered permeability, fusogenicity and effective reactivity, in order to devise multi-responsive drug delivery carriers for the targeted therapy of cancer.
In particular, Sofou’s group performs fundamental studies on the formation of heterogeneities on lipid bilayers: e.g. kinetics of formation and growth of lipid rafts on giant lipid vesicles. Transbilayer pH-gradients are exploited in order to alter the balance among electrostatic, hydrogen bonding, and Van der Waals interactions among lipids, therefore, resulting in formation of lateral heterogeneities. Lipid leaflet coupling, transbilayer registration of heterogeneities, and reversibility and kinetics of the formation of heterogeneites are among the issues of interest. Sofou’s translational agenda is to establish at NYU-Poly a research program focused on Drug Delivery. The multi- responsive drug delivery carriers designed by her group are a paradigm of enabling technology: they are excellent carriers for therapeutics and contrast agents for early diagnosis, and can be used as carriers for vaccination or to transport therapeutics against cancerous tumors.
Synamical Systems
The dynamical systems laboratory (DSL) directed by Dr. Porfiri conducts fundamental research in the broad field of modeling and control of complex dynamical systems with specialized expertise in smart materials and multifunctional structures for underwater applications. Activities span applied mathematics, design and fabrication of novel hardware, and advanced computations.
A central research theme in the DSL is the development of mathematical models for ionic polymer metal composites in aqueous environments towards the design of underwater sensors, actuators, and energy harvesting systems. An ionic polymer metal composite is composed of an ionomeric membrane that is saturated by an electrolytic solution and plated by noble metal electrodes. Chemo-electro-mechanical sensing and actuation in these materials is largely dictated by diffuse charge layers and chemical reactions at the ionomer-electrode interface. The DSL has developed rigorous mathematical models for determining the influence of the physical and geometrical properties of the ionomer-electrode interface on the complex response of ionic polymer metal composites. Such models are currently being used to engineer optimal surface structures for biomimetic underwater propulsion, dynamic pressure sensing, and harvesting of energy from coherent fluid structures and ambient vibrations.
Nanocomposites
Composite Materials and Mechanics Laboratory (CMML) is one of the leaders in hollow particle filled composites. The laboratory is directed by Dr. Nikhil Gupta and is focused on developing novel material microstructures, structural health monitoring techniques, and applications of lightweight materials in military and civilian structure. Interfaces play an important role in composite materials, especially in defining their fracture behavior. A new microstructure of hollow particle filled composites is designed in CMML, which is based on creating a gradient of hollow particles according to their wall thickness in the composite. Compared to the popular approach of creating particle volume fraction gradient, the new material provides advantage that the particle-matrix interfacial area is maintained constant throughout the structure and the interface can be independently used to tailor the material properties. Multiscale reinforced materials having two different reinforcement scales are also being investigated for their effectiveness in energy absorption. The applications of such structure are envisioned in blast resistant armors, spacecraft structures, and artificial bone segments.
The laboratory is also active in investigating porous biomaterials in order to create porous bio-inspired composite materials. The current theme of work is directed towards characterizing biomaterials for compressive, impact, and shock response through experimental and finite element analysis studies. The knowledge obtained from the testing will be used in designing multifunctional composites that closely mimic the physical and mechanical properties of bones. Porous composites present possibilities of inducing additional functionalities such as controlled drug delivery in these engineered structures, which will be explored.
NYU Dental School
Van Thompson, DDS, PhD
http://www.nyu.edu/gsas/program/biomaterials/vpthompson.htm
Professor and Chair, Department of Biomaterials and Biomimetics
van.thompson@nyu.edu
212-998-9638
Daniel Malamud, PhD
http://www.nyu.edu/dental/faculty/bios/ft/dm111
Professor , Basic Science and Craniofacial Biology
daniel.malamud@nyu.edu
212-998-9331
John Ricci, PhD
http://www.nyu.edu/gsas/program/biomaterials/jlricci.htm
Associate Professor, Department of Biomaterials and Biomimetics
john.ricci@nyu.edu
Timothy Bromage, PhD
http://www.nyu.edu/dental/faculty/bios/bio/tgb3
Adjunct Professor, Biomaterials and Biomimetics
tim.bromage@nyu.edu
212-998-9597
Paulo Coelho
Assistant Professor, Biomaterials, College of Dentistry
Louis Terracio
http://www.nyu.edu/dental/faculty/bios/ft/lt34
Professor, Basic Science and Craniofacial Biology
louis.terracio@nyu.edu
212-998-9917
NYU Medical School
Achiau Ludomirsky, MD
http://www.med.nyu.edu/people/ludoma01.html#
Chief, Pediatric Cardiology
Achi.Ludomirsky@nyumc.org
212 263 5940
Bruce Cronstein
http://www.med.nyu.edu/people/cronsb01.html
Director, Clinical and Translational Science Institute
Bruce.Cronstein@nyumc.org
212 263 6404
Chaim B. Reich, MD
http://www.med.nyu.edu/people/cbr1.html
Assistant Professor, Department of Medicine
Chaim.Reich@nyumc.org
212 263 7235
Daniel Antonius, PhD
http://psych-institute.med.nyu.edu/node/492
Assistant Professor, Department of Psychiatry
David Rapoport, MD
http://www.med.nyu.edu/research/rapopd01.html
Director, Sleep Medicine Program
David.Rapoport@nyumc.org
212 263 6407
Derya Unutmaz, MD
http://pathology.med.nyu.edu/people/faculty/unutmaz-derya
Associate Professor of Microbiology and Pathology
Derya.Unutmaz@nyumc.org
212 263 9203
Frederick Naftolin, MD, PhD
http://www.kronosinstitute.org/about/governance/advisoryboard/frederick_naftolin.cfm
Director, Reproductive Biology Research
George Foltin, MD, FAAP, FACEP
http://www.ahrq.gov/news/ulp/btpediatric/foltintxt.htm
Director, Center for Pediatric Emergency Medicine Bellevue Hospital
Hailing Liu, MD
Department of Medicine, Division of Clinical Pharmacology
Lung-Chi Chen, PhD
http://www.med.nyu.edu/people/lcc4.html
Professor, Department of Environmental Medicine
Lung-Chi.Chen@nyumc.org
845 731 3560
Marc Bloom, MD, PhD
http://www.med.nyu.edu/people/bloomm03.html
Clinical Associate Professor, Department of Anesthesiology
Marc.Bloom@nyumc.org
212 263 5072
Michael Dustin, PhD
http://pathology.med.nyu.edu/people/faculty/dustin-michael
Professor, Department of Pathology
michael.dustin@med.nyu.edu
212 263 3207 - 212 263 6282
Michelle Krogsgaard, PhD
http://pathology.med.nyu.edu/people/faculty/krogsgaard-michelle
Asst Professor, Pathology and NYU Cancer Institute
Michelle.Krogsgaard@nyumc.org
212 263 9266
Nandor Ludvig, MD, PhD
http://www.med.nyu.edu/people/ludvin01.html
Associate Professor, NYU Comprehensive Epilepsy Center
Nandor.Ludvig@nyumc.org
718 270 1796
Paul Pevsner, MD
http://www.med.nyu.edu/people/pevsnp01.html
Research Associate Professor, Depts. Of Pharmacology & Radiation Oncology
Paul.Pevsner@nyumc.org
212 263 0233
Peter S. Walker, PhD
Department of Orthopaedics
Peter.Walker@nyumc.org
212 353 4326
Thomas Franke, PhD, MD
http://www.med.nyu.edu/people/frankt03.html
Departments of Psychiatry and Pharmacology
Thomas.Franke@nyumc.org
212 263 5521
Thorsten Kirsch, PhD
http://www.med.nyu.edu/people/kirsct01.html
Director, Musculoskeletal Research Center
Thorsten.Kirsch@nyumc.org
212 598 6589
Doris Tse, PhD
Center for AIDS Research
Boyce Griffith, MD
Assistant Professor, Department of Cardiology
Boyce.Griffith@nyumc.org
212 263 4131
Bud Mishra, PhD
http://cs.nyu.edu/cs/faculty/mishra/
Professor, Department of Cell Biology
Mario Svirsky, PhD
http://www.med.nyu.edu/people/svirsm01.html
Professor, Department of Otolaryngology
Mario.Svirsky@NYUMC.ORG
212 263 7217
Sally Frenkel, PhD
http://mrc.med.nyu.edu/laboratories/sally-frenkel
Associate Professor, Depts of Orthopedic Surgery and Cell Biology
Sally.Frenkel@nyumc.org
212 598 6563
Thomas Thesen, PhD
http://www.med.nyu.edu/people/theset01.html
Assistant Professor, Department of Neurology
thomas.thesen@nyumc.org