Bio

Bio


Melosh's research is focused on developing methods to detect and control chemical processes on the nanoscale, to create materials that are responsive to their local environment. The research goal incorporates many of the hallmarks of biological adaptability, based on feedback control between cellular receptors and protein expression. Similar artificial networks may be achieved by fabricating arrays of nanoscale devices that can detect and influence their local surroundings through ionic potential, temperature, mechanical motion, capacitance, or electrochemistry. These devices are particularly suited as smart biomaterials, where multiple surface-cell interactions must be monitored and adjusted simultaneously for optimal cell adhesion and growth. Other interests include precise control over self-assembled materials, and potential methods to monitor the diagnostics of complicated chemical systems, such as the effect of drug treatments within patients.

Research Interests:
Molecular materials at interfaces
Directed dynamic self-assembly
Controlling molecular or biomolecular assembly and behavior
Influence of local electronic, optical or thermal stimuli

Academic Appointments


Professional Education


  • PhD, University of California at Santa Barbara, Materials Science and Engineering (2001)
  • BS, Harvey Mudd College, Chemistry (1996)

Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • Nanostraw-electroporation system for highly efficient intracellular delivery and transfection. ACS nano Xie, X., Xu, A. M., Leal-Ortiz, S., Cao, Y., Garner, C. C., Melosh, N. A. 2013; 7 (5): 4351-4358

    Abstract

    Nondestructive introduction of genes, proteins, and small molecules into mammalian cells with high efficiency is a challenging, yet critical, process. Here we demonstrate a simple nanoelectroporation platform to achieve highly efficient molecular delivery and high transfection yields with excellent uniformity and cell viability. The system is built on alumina nanostraws extending from a track-etched membrane, forming an array of hollow nanowires connected to an underlying microfluidic channel. Cellular engulfment of the nanostraws provides an intimate contact, significantly reducing the necessary electroporation voltage and increasing homogeneity over a large area. Biomolecule delivery is achieved by diffusion through the nanostraws and enhanced by electrophoresis during pulsing. The system was demonstrated to offer excellent spatial, temporal, and dose control for delivery, as well as providing high-yield cotransfection and sequential transfection.

    View details for DOI 10.1021/nn400874a

    View details for PubMedID 23597131

  • Measurement of elastic properties in fluid using high bandwidth atomic force microscope probes APPLIED PHYSICS LETTERS Vijayraghavan, K., Wang, A., Solgaard, O., Butte, M. J., Melosh, N. A. 2013; 102 (10)

    View details for DOI 10.1063/1.4795598

    View details for Web of Science ID 000316501200074

  • Microbead-separated thermionic energy converter with enhanced emission current PHYSICAL CHEMISTRY CHEMICAL PHYSICS Littau, K. A., Sahasrabuddhe, K., Barfield, D., Yuan, H., Shen, Z., Howe, R. T., Melosh, N. A. 2013; 15 (34): 14442-14446

    Abstract

    The efficiency of thermionic energy converters is a strong function of the inter-electrode separation due to space-charge limitations. Here we demonstrate vacuum thermionic energy converters constructed using barium dispenser cathodes and thin film tungsten anodes, separated by size specific alumina microbeads for simple device fabrication and inter-electrode gap control. The current and device efficiency at the maximum power point are strongly dependent on the inter-electrode gap, with a maximum device efficiency of 0.61% observed for a gap on the order of 5 μm. Paths to further reductions in space charge and improved anode work function are outlined with potential for over an order of magnitude improvement in output power and efficiency.

    View details for DOI 10.1039/c3cp52895b

    View details for Web of Science ID 000322725000036

    View details for PubMedID 23881241

  • Photon-enhanced thermionic emission from heterostructures with low interface recombination. Nature communications Schwede, J. W., Sarmiento, T., NARASIMHAN, V. K., Rosenthal, S. J., Riley, D. C., Schmitt, F., Bargatin, I., Sahasrabuddhe, K., Howe, R. T., Harris, J. S., Melosh, N. A., Shen, Z. 2013; 4: 1576-?

    Abstract

    Photon-enhanced thermionic emission is a method of solar-energy conversion that promises to combine photon and thermal processes into a single mechanism, overcoming fundamental limits on the efficiency of photovoltaic cells. Photon-enhanced thermionic emission relies on vacuum emission of photoexcited electrons that are in thermal equilibrium with a semiconductor lattice, avoiding challenging non-equilibrium requirements and exotic material properties. However, although previous work demonstrated the photon-enhanced thermionic emission effect, efficiency has until now remained very low. Here we describe electron-emission measurements on a GaAs/AlGaAs heterostructure that introduces an internal interface, decoupling the basic physics of photon-enhanced thermionic emission from the vacuum emission process. Quantum efficiencies are dramatically higher than in previous experiments because of low interface recombination and are projected to increase another order of magnitude with more stable, low work-function coatings. The results highlight the effectiveness of the photon-enhanced thermionic emission process and demonstrate that efficient photon-enhanced thermionic emission is achievable, a key step towards realistic photon-enhanced thermionic emission based energy conversion.

    View details for DOI 10.1038/ncomms2577

    View details for PubMedID 23481384

  • Power-independent wavelength determination by hot carrier collection in metal-insulator-metal devices. Nature communications Wang, F., Melosh, N. A. 2013; 4: 1711-?

    Abstract

    Wavelength separation and detection is generally performed by spatial dispersal of incident light onto separate detectors, or by appropriate wavelength-selective filters. Here we demonstrate direct wavelength determination of monochromatic light in a power-independent fashion with a single metal-insulator-metal device. This simple platform allows facile fabrication and scaling, and may be useful for on-chip optical communications. Although a single wavelength is power-independent, with two or more concurrent input signals, the output obeys a simple current sum rule, allowing the output to be tuned by choosing the input wavelengths and power. Finally, we demonstrate real-time deconvolution of three different wavelength asynchronous signals.

    View details for DOI 10.1038/ncomms2728

    View details for PubMedID 23591878

  • Nanostraw–Electroporation System for Highly Efficient Intracellular Delivery and Transfection Acs Nano Xie, X., Xu, A., M., Leal-Ortiz, S., Cao, Y., Garner, C., C., Melosh, N., A. 2013
  • Power-independent wavelength determination by hot carrier collection in metal-insulator-metal devices Nat Commun Wang, F., Melosh, N., A. 2013; 4: 1711
  • Measurement of elastic properties in fluid using high bandwidth atomic force microscope probes Applied Physics Letters Vijayraghavan, K., Wang, A., Solgaard, O., Butte, M., J., Melosh, N., A. 2013; 102: 103111 (4 pp.)-103111 (4 pp.)
  • Photon-enhanced thermionic emission from heterostructures with low interface recombination Nat Commun Schwede, J., W., Sarmiento, T., Narasimhan, V., K., Rosenthal, S., J., Riley, D., C., Schmitt, F., Melosh, Nicholas, A. 2013; 4: 1576
  • Photocathode device using diamondoid and cesium bromide films APPLIED PHYSICS LETTERS Clay, W. A., Maldonado, J. R., Pianetta, P., Dahl, J. E., Carlson, R. M., Schreiner, P. R., Fokin, A. A., Tkachenko, B. A., Melosh, N. A., Shen, Z. 2012; 101 (24)

    View details for DOI 10.1063/1.4769043

    View details for Web of Science ID 000312490000024

  • A model for emission yield from planar photocathodes based on photon-enhanced thermionic emission or negative-electron-affinity photoemission JOURNAL OF APPLIED PHYSICS Sahasrabuddhe, K., Schwede, J. W., Bargatin, I., Jean, J., Howe, R. T., Shen, Z., Melosh, N. A. 2012; 112 (9)

    View details for DOI 10.1063/1.4764106

    View details for Web of Science ID 000311968400139

  • Diamondoid coating enables disruptive approach for chemical and magnetic imaging with 10 nm spatial resolution APPLIED PHYSICS LETTERS Ishiwata, H., Acremann, Y., Scholl, A., Rotenberg, E., Hellwig, O., Dobisz, E., Doran, A., Tkachenko, B. A., Fokin, A. A., Schreiner, P. R., Dahl, J. E., Carlson, R. M., Melosh, N., Shen, Z., Ohldag, H. 2012; 101 (16)

    View details for DOI 10.1063/1.4756893

    View details for Web of Science ID 000310669300052

  • Nanostraws for Direct Fluidic Intracellular Access NANO LETTERS VanDersarl, J. J., Xu, A. M., Melosh, N. A. 2012; 12 (8): 3881-3886

    Abstract

    Nanomaterials are promising candidates to improve the delivery efficiency and control of active agents such as DNA or drugs directly into cells. Here we demonstrate cell-culture platforms of nanotemplated "nanostraws" that pierce the cell membrane, providing a permanent fluidic pipeline into the cell for direct cytosolic access. Conventional polymeric track-etch cell culture membranes are alumina coated and etched to produce fields of nanostraws with controllable diameter, thickness, and height. Small molecules and ions were successfully transported into the cytosol with 40 and 70% efficiency, respectively, while GFP plasmids were successfully delivered and expressed. These platforms open the way for active, reproducible delivery of a wide variety of species into cells without endocytosis.

    View details for DOI 10.1021/nl204051v

    View details for Web of Science ID 000307211000001

    View details for PubMedID 22166016

  • Shape Matters: Intravital Microscopy Reveals Surprising Geometrical Dependence for Nanoparticles in Tumor Models of Extravasation NANO LETTERS Smith, B. R., Kempen, P., Bouley, D., Xu, A., Liu, Z., Melosh, N., Dai, H., Sinclair, R., Gambhir, S. S. 2012; 12 (7): 3369-3377

    Abstract

    Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous.

    View details for DOI 10.1021/nl204175t

    View details for Web of Science ID 000306296200004

    View details for PubMedID 22650417

  • Optimal emitter-collector gap for thermionic energy converters APPLIED PHYSICS LETTERS Lee, J., Bargatin, I., Melosh, N. A., Howe, R. T. 2012; 100 (17)

    View details for DOI 10.1063/1.4707379

    View details for Web of Science ID 000303340300106

  • Mesoporous Thin-Film on Highly-Sensitive Resonant Chemical Sensor for Relative Humidity and CO2 Detection ANALYTICAL CHEMISTRY Lee, H. J., Park, K. K., Kupnik, M., Melosh, N. A., Khuri-Yakub, B. T. 2012; 84 (7): 3063-3066

    Abstract

    Distributed sensing of gas-phase chemicals is a promising application for mesoporous materials when combined with highly sensitive miniaturized gas sensors. We present a direct application of a mesoporous silica thin film on a highly sensitive miniaturized resonant chemical sensor with a mass sensitivity at the zeptogram scale for relative humidity and CO(2) detection. Using mesoporous silica thin-film, we report one of the lowest volume resolutions and a sensitive detection of 5.1 × 10(-4)% RH/Hz to water vapor in N(2), which is 70 times higher than a device with a nontemplated silica layer. In addition, a mesoporous thin-film that is functionalized with an amino-group is directly applied on the resonant sensor, which exhibits a volume sensitivity of 1.6 × 10(-4)%/Hz and a volume resolution of 1.82 × 10(-4)% to CO(2) in N(2).

    View details for DOI 10.1021/ac300225c

    View details for Web of Science ID 000302829800006

    View details for PubMedID 22372606

  • Photocathode device using diamondoid and cesium bromide films Applied Physics Letters Clay, W., A., Maldonado, J., R., Pianetta, P., Dahl, J., E.P., Carlson, R., M.K., Schreiner, P., R., Melosh, Nicholas, A. 2012; 101: 241605 (5 pp.)-241605 (5 pp.)
  • Diamondoid coating enables disruptive approach for chemical and magnetic imaging with 10 nm spatial resolution Applied Physics Letters Ishiwata, H., Acremann, Y., Scholl, A., Rotenberg, E., Hellwig, O., Dobisz, E., Melosh, Nicholas, A. 2012; 101: 163101 (5 pp.)-163101 (5 pp.)163101 (5 pp.)
  • Optimal emitter-collector gap for thermionic energy converters Applied Physics Letters Lee, J., H., Bargatin, I., Melosh, N., A., Howe, R., T. 2012; 100
  • A model for emission yield from planar photocathodes based on photon-enhanced thermionic emission or negative-electron-affinity photoemission Journal of Applied Physics Sahasrabuddhe, K., Schwede, J., W., Bargatin, I., Jean, J., Howe, R., T., Shen, Z., X., Melosh, Nicholas, A. 2012; 112: 094907 (10 pp.)-094907 (10 pp.)094907 (10 pp.)
  • Plasmonic Energy Collection through Hot Carrier Extraction NANO LETTERS Wang, F., Melosh, N. A. 2011; 11 (12): 5426-5430

    Abstract

    Conversion of light into direct current is important for applications ranging from energy conversion to photodetection, yet often challenging over broad photon frequencies. Here we show a new architecture based on surface plasmon excitation within a metal-insulator-metal device that produces power based on spatial confinement of electron excitation through plasmon absorption. Plasmons excited in the upper metal are absorbed, creating a high concentration of hot electrons which can inject above or tunnel through the thin insulating barrier, producing current. The theoretical power conversion efficiency enhancement achieved can be almost 40 times larger than that of direct illumination while utilizing a broad spectrum of IR to visible wavelengths. Here we present both theoretical estimates of the power conversion efficiency and experimental device measurements, which show clear rectification and power conversion behavior.

    View details for DOI 10.1021/nl203196z

    View details for Web of Science ID 000297950200056

    View details for PubMedID 22023372

  • Photoluminescence of diamondoid crystals JOURNAL OF APPLIED PHYSICS Clay, W. A., Sasagawa, T., Iwasa, A., Liu, Z., Dahl, J. E., Carlson, R. M., Kelly, M., Melosh, N., Shen, Z. 2011; 110 (9)

    View details for DOI 10.1063/1.3657522

    View details for Web of Science ID 000297062100028

  • Molecular Structure Influences the Stability of Membrane Penetrating Biointerfaces NANO LETTERS Almquist, B. D., Melosh, N. A. 2011; 11 (5): 2066-2070

    Abstract

    Nanoscale patterning of hydrophobic bands on otherwise hydrophilic surfaces allows integration of inorganic structures through biological membranes, reminiscent of transmembrane proteins. Here we show that a set of innate molecular properties of the self-assembling hydrophobic band determine the resulting interface stability. Surprisingly, hydrophobicity is found to be a secondary factor with monolayer crystallinity the major determinate of interface strength. These results begin to establish guidelines for seamless bioinorganic integration of nanoscale probes with lipid membranes.

    View details for DOI 10.1021/nl200542m

    View details for Web of Science ID 000290373000037

    View details for PubMedID 21469728

  • Rapid spatial and temporal controlled signal delivery over large cell culture areas LAB ON A CHIP VanDersarl, J. J., Xu, A. M., Melosh, N. A. 2011; 11 (18): 3057-3063

    Abstract

    Controlled chemical delivery in microfluidic cell culture devices often relies on slowly evolving diffusive gradients, as the spatial and temporal control provided by fluid flow results in significant cell-perturbation. In this paper we introduce a microfluidic device architecture that allows for rapid spatial and temporal soluble signal delivery over large cell culture areas without fluid flow over the cells. In these devices the cell culture well is divided from a microfluidic channel located directly underneath the chamber by a nanoporous membrane. This configuration requires chemical signals in the microchannel to only diffuse through the thin membrane into large cell culture area, rather than diffuse in from the sides. The spatial chemical pattern within the microfluidic channel was rapidly transferred to the cell culture area with good fidelity through diffusion. The cellular temporal response to a step-function signal showed that dye reached the cell culture surface within 45 s, and achieved a static concentration in under 6 min. Chemical pulses of less than one minute were possible by temporally alternating the signal within the microfluidic channel, enabling rapid flow-free chemical microenvironment control for large cell culture areas.

    View details for DOI 10.1039/c1lc20311h

    View details for Web of Science ID 000294263400004

    View details for PubMedID 21805010

  • Nanoscale patterning controls inorganic-membrane interface structure NANOSCALE Almquist, B. D., Verma, P., Cai, W., Melosh, N. A. 2011; 3 (2): 391-400

    Abstract

    The ability to non-destructively integrate inorganic structures into or through biological membranes is essential to realizing full bio-inorganic integration, including arrayed on-chip patch-clamps, drug delivery, and biosensors. Here we explore the role of nanoscale patterning on the strength of biomembrane-inorganic interfaces. AFM measurements show that inorganic probes functionalized with hydrophobic bands with thicknesses complimentary to the hydrophobic lipid bilayer core exhibit strong attachment in the bilayer. As hydrophobic band thickness increases to 2-3 times the bilayer core the interfacial strength decreases, comparable to homogeneously hydrophobic probes. Analytical calculations and molecular dynamics simulations predict a transition between a 'fused' interface and a 'T-junction' that matches the experimental results, showing lipid disorder and defect formation for thicker bands. These results show that matching biological length scales leads to more intimate bio-inorganic junctions, enabling rational design of non-destructive membrane interfaces.

    View details for DOI 10.1039/c0nr00486c

    View details for Web of Science ID 000287363500006

    View details for PubMedID 20931126

  • Photoluminescence of Diamond Crystals Journal of Applied Physics Clay, W., A., Sasagawa, T., Iwasa, A., Liu, Z., Dahl, J., E., Carlson, R., M.K., Melosh, Nicholas, A. 2011
  • Plasmonic energy collection through hot carrier extraction Nano Letters Wang, F., Melosh, N., A. 2011; 11: 5426-30
  • Nanostraws for Direct Fluidic Intracellular Access Nano Letters Vandersarl, J., J., Xu, A., M., Melosh, N., A. 2011
  • ENZYME ASSAYS Detection by failure NATURE CHEMISTRY Melosh, N. A. 2010; 2 (12): 1006-1007

    View details for DOI 10.1038/nchem.914

    View details for Web of Science ID 000284527300004

    View details for PubMedID 21107359

  • Effects of tip-induced material reorganization in dynamic force spectroscopy PHYSICAL REVIEW E Hager-Barnard, E. A., Melosh, N. A. 2010; 82 (3)

    Abstract

    Dynamic force spectroscopy (DFS) has become a well-established method for characterizing bond strength, yet may also be useful for examining more complex phenomena such as dynamic processes or multiple reaction pathways. Here, we analyze the case where contact between an atomic force microscopy (AFM) tip and the sample induces sample reorganization during testing. Surface contact often causes molecular rearrangement in soft materials, which could also result in an altered reaction energy landscape. We model this situation by allowing the energy barrier position and magnitude to be time-dependent functions with a characteristic time scale ? . We find dynamic energy barriers result in two linear regimes with a dramatic transition near t=? in the DFS analysis. The sharp transition region is a hallmark of a moving energy barrier and indicates the time scale of reorganization. These results illustrate that DFS may be useful to monitor dynamic transitions and also highlight the importance of extending the loading rate range used in DFS studies.

    View details for DOI 10.1103/PhysRevE.82.031911

    View details for Web of Science ID 000282133400008

    View details for PubMedID 21230112

  • Photon-enhanced thermionic emission for solar concentrator systems NATURE MATERIALS Schwede, J. W., Bargatin, I., Riley, D. C., Hardin, B. E., Rosenthal, S. J., Sun, Y., Schmitt, F., Pianetta, P., Howe, R. T., Shen, Z., Melosh, N. A. 2010; 9 (9): 762-767

    Abstract

    Solar-energy conversion usually takes one of two forms: the 'quantum' approach, which uses the large per-photon energy of solar radiation to excite electrons, as in photovoltaic cells, or the 'thermal' approach, which uses concentrated sunlight as a thermal-energy source to indirectly produce electricity using a heat engine. Here we present a new concept for solar electricity generation, photon-enhanced thermionic emission, which combines quantum and thermal mechanisms into a single physical process. The device is based on thermionic emission of photoexcited electrons from a semiconductor cathode at high temperature. Temperature-dependent photoemission-yield measurements from GaN show strong evidence for photon-enhanced thermionic emission, and calculated efficiencies for idealized devices can exceed the theoretical limits of single-junction photovoltaic cells. The proposed solar converter would operate at temperatures exceeding 200 degrees C, enabling its waste heat to be used to power a secondary thermal engine, boosting theoretical combined conversion efficiencies above 50%.

    View details for DOI 10.1038/NMAT2814

    View details for Web of Science ID 000281178400029

    View details for PubMedID 20676086

  • Gigaohm resistance membrane seals with stealth probe electrodes APPLIED PHYSICS LETTERS Verma, P., Melosh, N. A. 2010; 97 (3)

    View details for DOI 10.1063/1.3464954

    View details for Web of Science ID 000280255800104

  • An Electrostatic Model for DNA Surface Hybridization BIOPHYSICAL JOURNAL Wong, I. Y., Melosh, N. A. 2010; 98 (12): 2954-2963

    Abstract

    DNA hybridization at surfaces is a crucial process for biomolecular detection, genotyping, and gene expression analysis. However, hybridization density and kinetics can be strongly inhibited by electric fields from the negatively charged DNA as the reaction proceeds. Here, we develop an electrostatic model to optimize hybridization density and kinetics as a function of DNA surface density, salt concentrations, and applied voltages. The electrostatic repulsion from a DNA surface layer is calculated numerically and incorporated into a modified Langmuir scheme, allowing kinetic suppression of hybridization. At the low DNA probe densities typically used in assays (<10(13)/cm(2)), electrostatics effects are largely screened and hybridization is completed with fast kinetics. However, higher hybridization densities can be achieved at intermediate DNA surface densities, albeit with slower kinetics. The application of positive voltages circumvents issues resulting from the very high DNA probe density, allowing highly enhanced hybridization densities and accelerated kinetics, and validating recent experimental measurements.

    View details for DOI 10.1016/j.bpj.2010.03.017

    View details for Web of Science ID 000278913500024

    View details for PubMedID 20550908

  • Dynamic actuation using nano-bio interfaces MATERIALS TODAY Wong, I. Y., Almquist, B. D., Melosh, N. A. 2010; 13 (6): 14-22
  • Continuum model of mechanical interactions between biological cells and artificial nanostructures BIOINTERPHASES Verma, P., Wong, I. Y., Melosh, N. A. 2010; 5 (2): 37-44

    Abstract

    The controlled insertion of artificial nanostructures into biological cells has been utilized for patch clamping, targeted drug delivery, cell lysing, and cell mechanics measurements. In this work, an elastic continuum model is implemented to treat the deformation of spherical cells in solution due to their interaction with cylindrical probes. At small deformations, the force varies nonlinearly with indentation due to global deformation of the cell shape. However, at large indentations, the force varies linearly with indentation due to more localized deformations. These trends are consistent with experimental measurements under comparable conditions and can be used to develop design rules for optimizing probe-cell interactions.

    View details for DOI 10.1116/1.3431960

    View details for Web of Science ID 000282333300003

    View details for PubMedID 20831347

  • Single-Step Process to Reconstitute Cell Membranes on Solid Supports LANGMUIR Mager, M. D., Melosh, N. A. 2010; 26 (7): 4635-4638

    Abstract

    A new technique is presented to create supported lipid bilayers from whole cell lipids without the use of detergent or solvent extraction. In a modification of the bubble collapse deposition (BCD) technique, an air bubble is created underwater and brought into contact with a population of cells. The high-energy air/water interface extracts the lipid component of the cell membrane, which can subsequently be redeposited as a fluid bilayer on another substrate. The resulting bilayers were characterized with fluorescence microscopy, and it was found that both leaflets of the cell membrane are transferred but the cytoskeleton is not. The resulting supported bilayer was fluid over an area much larger than a single cell, demonstrating the capacity to create large, continuous bilayer samples. This capability to create fluid, biologically relevant bilayers will facilitate the use of high-resolution scanning microscopy techniques in the study of membrane-related processes.

    View details for DOI 10.1021/la100583f

    View details for Web of Science ID 000275995100020

    View details for PubMedID 20205459

  • Fusion of biomimetic stealth probes into lipid bilayer cores PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Almquist, B. D., Melosh, N. A. 2010; 107 (13): 5815-5820

    Abstract

    Many biomaterials are designed to regulate the interactions between artificial and natural surfaces. However, when materials are inserted through the cell membrane itself the interface formed between the interior edge of the membrane and the material surface is not well understood and poorly controlled. Here we demonstrate that by replicating the nanometer-scale hydrophilic-hydrophobic-hydrophilic architecture of transmembrane proteins, artificial "stealth" probes spontaneously insert and anchor within the lipid bilayer core, forming a high-strength interface. These nanometer-scale hydrophobic bands are readily fabricated on metallic probes by functionalizing the exposed sidewall of an ultrathin evaporated Au metal layer rather than by lithography. Penetration and adhesion forces for butanethiol and dodecanethiol functionalized probes were directly measured using atomic force microscopy (AFM) on thick stacks of lipid bilayers to eliminate substrate effects. The penetration dynamics were starkly different for hydrophobic versus hydrophilic probes. Both 5- and 10 nm thick hydrophobically functionalized probes naturally resided within the lipid core, while hydrophilic probes remained in the aqueous region. Surprisingly, the barrier to probe penetration with short butanethiol chains (E(o,5 nm) = 21.8k(b)T, E(o,10 nm) = 15.3k(b)T) was dramatically higher than longer dodecanethiol chains (E(o,5 nm) = 14.0k(b)T, E(o,10 nm) = 10.9k(b)T), indicating that molecular mobility and orientation also play a role in addition to hydrophobicity in determining interface stability. These results highlight a new strategy for designing artificial cell interfaces that can nondestructively penetrate the lipid bilayer.

    View details for DOI 10.1073/pnas.0909250107

    View details for Web of Science ID 000276159500024

    View details for PubMedID 20212151

  • Gigaohm resistance membrane seals with stealth probe electrodes Applied Physics Letters Verma, P., Melosh, N., A. 2010; 97
  • Effects of tip-induced material reorganization in dynamic force spectroscopy Phys. Rev. E Hager-Barnard, E., Melosh, N., A. 2010; 82: 31911
  • ENZYME ASSAYS: Detection by failure Nature Chemistry Melosh, N., A. 2010; 2: 1006-1007
  • Directed Hybridization and Melting of DNA Linkers using Counterion-Screened Electric Fields NANO LETTERS Wong, I. Y., Melosh, N. A. 2009; 9 (10): 3521-3526

    Abstract

    Dynamic self-assembly using responsive, "smart" materials such as DNA is a promising route toward reversible assembly and patterning of nanostructures for error-corrected fabrication, enhanced biosensors, drug delivery and gene therapy. DNA linkers were designed with strategically placed mismatches, allowing rapid attachment and release from a surface in a counterion-screened electric field. These electrostatic fields are inherently highly localized, directing assembly with nanometer precision while avoiding harmful electrochemical reactions. We show that depending on the sign of the applied field, the DNA hybridization density is strongly enhanced or diminished due to the high negative charge density of immobilized DNA. This use of dynamic fields rather than static templates enables fabrication of heterogeneously hybridized electrodes with different functional moieties, despite the use of identical linker sequences.

    View details for DOI 10.1021/nl901710n

    View details for Web of Science ID 000270670500025

    View details for PubMedID 19606816

  • Determining orientational structure of diamondoid thiols attached to silver using near-edge X-ray absorption fine structure spectroscopy JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA Willey, T. M., Lee, J. R., Fabbri, J. D., Wang, D., Nielsen, M. H., Randel, J. C., Schreiner, P. R., Fokin, A. A., Tkachenko, B. A., Fokina, N. A., Dahl, J. E., Carlson, R. M., Terminello, L. J., Melosh, N. A., van Buuren, T. 2009; 172 (1-3): 69-77
  • Identification and Passivation of Defects in Self-Assembled Monolayers LANGMUIR Preiner, M. J., Melosh, N. A. 2009; 25 (5): 2585-2587

    Abstract

    We demonstrate imaging of nanoscale defects in self-assembled monolayers (SAMs). Atomic layer deposition of aluminum oxide (AlO(x)) onto hydrophobic SAMs is followed by imaging using scanning electron microscopy (SEM). The insulating AlO(x) selectively deposits onto the exposed substrate at defect sites and becomes charged during imaging, providing high contrast even for nanometer scale defects. The deposited AlO(x) also acts as a barrier for electron transfer, thereby simultaneously electrically passivating the defects in the SAM as it labels them.

    View details for DOI 10.1021/la804162a

    View details for Web of Science ID 000263770800009

    View details for PubMedID 19437743

  • Determining orientational structure of diamondoid thiols attached to silver using near-edge X-ray absorption fine structure spectroscopy Journal of Electron Spectroscopy and Related Phenomena Willey, T., M., Lee, J., R.I., Fabbri, J., D., Wang, D., Nielsen, M., H., Randel, J., C., Melosh, Nicholas, A. 2009; 172: 69-77
  • Origin of the Monochromatic Photoemission Peak in Diamondoid Monolayers NANO LETTERS Clay, W. A., Liu, Z., Yang, W., Fabbri, J. D., Dahl, J. E., Carlson, R. M., Sun, Y., Schreiner, P. R., Fokin, A. A., Tkachenko, B. A., Fokina, N. A., Pianetta, P. A., Melosh, N., Shen, Z. 2009; 9 (1): 57-61

    Abstract

    Recent photoemission experiments have discovered a highly monochromatized secondary electron peak emitted from diamondoid self-assembled monolayers on metal substrates. New experimental data and simulation results are presented to show that a combination of negative electron affinity and strong electron-phonon scattering is responsible for this behavior. The simulation results are generated using a simple Monte Carlo transport algorithm. The simulated spectra recreate the main spectral features of the measured ones.

    View details for DOI 10.1021/nl802310k

    View details for Web of Science ID 000262519100010

    View details for PubMedID 18975993

  • Nanopore-Spanning Lipid Bilayers for Controlled Chemical Release ADVANCED MATERIALS Mager, M. D., Melosh, N. A. 2008; 20 (23): 4423-4427
  • Formation and Characterization of Fluid Lipid Bilayers on Alumina LANGMUIR Mager, M. D., Almquist, B., Melosh, N. A. 2008; 24 (22): 12734-12737

    Abstract

    Fluid lipid bilayers were deposited on alumina substrates with the use of bubble collapse deposition (BCD). Previous studies using vesicle rupture have required the use of charged lipids or surface functionalization to induce bilayer formation on alumina, but these modifications are not necessary with BCD. Photobleaching experiments reveal that the diffusion coefficient of POPC on alumina is 0.6 microm (2)/s, which is much lower than the 1.4-2.0 microm (2)/s reported on silica. Systematically accounting for roughness, immobile regions and membrane viscosity shows that pinning sites account for about half of this drop in diffusivity. The remainder of the difference is attributed to a more tightly bound water state on the alumina surface, which induces a larger drag on the bilayer.

    View details for DOI 10.1021/la802726u

    View details for Web of Science ID 000260874800004

    View details for PubMedID 18942863

  • Diamondoids as low-kappa dielectric materials APPLIED PHYSICS LETTERS Clay, W. A., Sasagawa, T., Kelly, M., Dahl, J. E., Carlson, R. M., Melosh, N., Shen, Z. 2008; 93 (17)

    View details for DOI 10.1063/1.3010379

    View details for Web of Science ID 000260571800066

  • Near-edge X-ray absorption fine structure spectroscopy of diamondoid thiol monolayers on gold JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Willey, T. M., Fabbri, J. D., Lee, J. R., Schreiner, P. R., Fokin, A. A., Tkachenko, B. A., Fokina, N. A., Dahl, J. E., Carlson, R. M., Vance, A. L., Yang, W., Terminello, L. J., van Buuren, T., Melosh, N. A. 2008; 130 (32): 10536-10544

    Abstract

    Diamondoids, hydrocarbon molecules with cubic-diamond-cage structures, have unique properties with potential value for nanotechnology. The availability and ability to selectively functionalize this special class of nanodiamond materials opens new possibilities for surface modification, for high-efficiency field emitters in molecular electronics, as seed crystals for diamond growth, or as robust mechanical coatings. The properties of self-assembled monolayers (SAMs) of diamondoids are thus of fundamental interest for a variety of emerging applications. This paper presents the effects of thiol substitution position and polymantane order on diamondoid SAMs on gold using near-edge X-ray absorption fine structure spectroscopy (NEXAFS) and X-ray photoelectron spectroscopy (XPS). A framework to determine both molecular tilt and twist through NEXAFS is presented and reveals highly ordered diamondoid SAMs, with the molecular orientation controlled by the thiol location. C 1s and S 2p binding energies are lower in adamantane thiol than alkane thiols on gold by 0.67 +/- 0.05 and 0.16 +/- 0.04 eV, respectively. These binding energies vary with diamondoid monolayer structure and thiol substitution position, consistent with different degrees of steric strain and electronic interaction with the substrate. This work demonstrates control over the assembly, in particular the orientational and electronic structure, providing a flexible design of surface properties with this exciting new class of diamond nanoparticles.

    View details for DOI 10.1021/ja711131e

    View details for Web of Science ID 000258293800038

    View details for PubMedID 18642809

  • Interfacial effects in thin films of polymeric semiconductors JOURNAL OF VACUUM SCIENCE & TECHNOLOGY B Rivnay, J., Jimison, L. H., Toney, M. F., Preiner, M., Melosh, N. A., Salleo, A. 2008; 26 (4): 1454-1460

    View details for DOI 10.1116/1.2952454

    View details for Web of Science ID 000258494400036

  • Electronically activated actin protein polymerization and alignment JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Wong, I. Y., Footer, M. J., Melosh, N. A. 2008; 130 (25): 7908-7915

    Abstract

    Biological systems are the paragon of dynamic self-assembly, using a combination of spatially localized protein complexation, ion concentration, and protein modification to coordinate a diverse set of self-assembling components. Biomimetic materials based upon biologically inspired design principles or biological components have had some success at replicating these traits, but have difficulty capturing the dynamic aspects and diversity of biological self-assembly. Here, we demonstrate that the polymerization of ion-sensitive proteins can be dynamically regulated using electronically enhanced ion mixing and monomer concentration. Initially, the global activity of the cytoskeletal protein actin is inhibited using a low-ionic strength buffer that minimizes ion complexation and protein-protein interactions. Nucleation and growth of actin filaments are then triggered by a low-frequency AC voltage, which causes local enhancement of the actin monomer concentration and mixing with Mg(2+). The location and extent of polymerization are governed by the voltage and frequency, producing highly ordered structures unprecedented in bulk experiments. Polymerization rate and filament orientation could be independently controlled using a combination of low-frequency (approximately 100 Hz) and high frequency (1 MHz) AC voltages, creating a range of macromolecular architectures from network hydrogel microparticles to highly aligned arrays of actin filaments with approximately 750 nm periodicity. Since a wide range of proteins are activated upon complexation with charged species, this approach may be generally applicable to a variety of biopolymers and proteins.

    View details for DOI 10.1021/ja7103284

    View details for Web of Science ID 000256962000042

    View details for PubMedID 18507467

  • Creating large area molecular electronic junctions using atomic layer deposition APPLIED PHYSICS LETTERS Preiner, M. J., Melosh, N. A. 2008; 92 (21)

    View details for DOI 10.1063/1.2917870

    View details for Web of Science ID 000256303500073

  • A nonvolatile plasmonic switch employing photochromic molecules NANO LETTERS Pala, R. A., Shimizu, K. T., Melosh, N. A., Brongersma, M. L. 2008; 8 (5): 1506-1510

    Abstract

    We demonstrate a surface plasmon-polariton (SPP) waveguide all-optical switch that combines the unique physical properties of small molecules and metallic (plasmonic) nanostructures. The switch consists of a pair of gratings defined in an aluminum film coated with a 65 nm thick layer of photochromic (PC) molecules. The first grating couples a signal beam consisting of free space photons to SPPs that interact effectively with the PC molecules. These molecules can reversibly be switched between transparent and absorbing states using a free space optical pump. In the transparent (signal "on") state, the SPPs freely propagate through the molecular layer, and in the absorbing (signal "off") state, the SPPs are strongly attenuated. The second grating serves to decouple the SPPs back into a free space optical beam, enabling measurement of the modulated signal with a far-field detector. In a preliminary study, the switching behavior of the PC molecules themselves was confirmed and quantified by surface plasmon resonance spectroscopy. The excellent (16%) overlap of the SPP mode profile with the thin layer of switching molecules enabled efficient switching with power densities of approximately 6.0 mW/cm2 in 1.5 microm x 8 microm devices, resulting in plasmonic switching powers of 0.72 nW per device. Calculations further showed that modulation depths in access of 20 dB can easily be attained in optimized designs. The quantitative experimental and theoretical analysis of the nonvolatile switching behavior in this letter guides the design of future nanoscale optically or electrically pumped optical switches.

    View details for DOI 10.1021/nl0808839

    View details for Web of Science ID 000255906400042

    View details for PubMedID 18412401

  • Efficient optical coupling into metal-insulator-metal plasmon modes with subwavelength diffraction gratings APPLIED PHYSICS LETTERS Preiner, M. J., Shimizu, K. T., White, J. S., Melosh, N. A. 2008; 92 (11)

    View details for DOI 10.1063/1.2898509

    View details for Web of Science ID 000254292400085

  • Diamondoids as low-kappa dielectric materials Applied Physics Letters Clay, W., A., Sasagawa, T., Kelly, M., Dahl, J., E., Carlson, R., M.K., Melosh, N. 2008; 93: 172901
  • Efficient optical coupling into metal-insulator-metal plasmon modes with subwavelength diffraction gratings Applied Physics Letters Preiner, M., J., Shimizu, K., T., White, J., S., Melosh, N., A. 2008; 92: 113109-1-3
  • Creating large area molecular electronic junctions using atomic layer deposition Applied Physics Letters Preiner, M., J., Melosh, N., A. 2008; 92
  • Lipid bilayer deposition and patterning via air bubble collapse LANGMUIR Mager, M. D., Melosh, N. A. 2007; 23 (18): 9369-9377

    Abstract

    We report a new method for forming patterned lipid bilayers on solid substrates. In bubble collapse deposition (BCD), an air bubble is first "inked" with a monolayer of phospholipid molecules and then touched to the surface of a thermally oxidized silicon wafer and the air is slowly withdrawn. As the bubble shrinks, the lipid monolayer pressure increases. Once the monolayer exceeds the collapse pressure, it folds back on itself, depositing a stable lipid bilayer on the surface. These bilayer disks have lateral diffusion coefficients consistent with high quality supported bilayers. By sequentially depositing bilayers in overlapping areas, fluid connections between bilayers of different compositions are formed. Performing vesicle rupture on the open substrate surrounding this bilayer patch results in a fluid but spatially isolated bilayer. Very little intermixing was observed between the vesicle rupture and bubble-deposited bilayers.

    View details for DOI 10.1021/la701372b

    View details for Web of Science ID 000248886700037

    View details for PubMedID 17683151

  • Monochromatic electron photoemission from diamondoid monolayers SCIENCE Yang, W. L., Fabbri, J. D., Willey, T. M., Lee, J. R., Dahl, J. E., Carlson, R. M., Schreiner, P. R., Fokin, A. A., Tkachenko, B. A., Fokina, N. A., Meevasana, W., Mannella, N., Tanaka, K., Zhou, X. J., van Buuren, T., Kelly, M. A., Hussain, Z., Melosh, N. A., Shen, Z. 2007; 316 (5830): 1460-1462

    Abstract

    We found monochromatic electron photoemission from large-area self-assembled monolayers of a functionalized diamondoid, [121]tetramantane-6-thiol. Photoelectron spectra of the diamondoid monolayers exhibited a peak at the low-kinetic energy threshold; up to 68% of all emitted electrons were emitted within this single energy peak. The intensity of the emission peak is indicative of diamondoids being negative electron affinity materials. With an energy distribution width of less than 0.5 electron volts, this source of monochromatic electrons may find application in technologies such as electron microscopy, electron beam lithography, and field-emission flat-panel displays.

    View details for DOI 10.1126/science.1141811

    View details for Web of Science ID 000247066400037

    View details for PubMedID 17556579

  • Monochromatic Electron Emission from Negative Electron Affinity Diamondoid Monolayers Science Yang, W., L., Fabbri, J., D., Willey, T., M., Lee, J., R.I., Dahl, J., E., Carlson, R., M.K., Melosh, Nicholas, A. 2007; 315: 1460-1462
  • Dynamic control of biomolecular activity using electrical interfaces SOFT MATTER Wong, I. Y., Footer, M. J., Melosh, N. A. 2007; 3 (3): 267-274

    View details for DOI 10.1039/b607279h

    View details for Web of Science ID 000246006700003

  • Probing molecular junctions using surface plasmon resonance spectroscopy NANO LETTERS Shimizu, K. T., Pala, R. A., Fabbri, J. D., Brongersma, M. L., Melosh, N. A. 2006; 6 (12): 2797-2803

    Abstract

    The optical absorption spectra of nanometer-thick organic films and molecular monolayers sandwiched between two metal contacts have been measured successfully using surface plasmon resonance spectroscopy (SPRS). The electric field within metal-insulator (organic)-metal (MIM) cross-bar junctions created by surface plasmon-polaritons excited on the metal surface allows sensitive measurement of molecular optical properties. Specifically, this spectroscopic technique extracts the real and imaginary indices of the organic layer for each wavelength of interest. The SPRS sensitivity was calculated for several device architectures, metals, and layer thicknesses to optimize the organic film absorptivity measurements. Distinct optical absorption features were clearly observed for R6G layers as thin as a single molecular monolayer between two metal electrodes. This method also enables dynamic measurement of molecular conformation inside metallic junctions, as shown by following the optical switching of a thin spiropyran/polymer film upon exposure to UV light. Finally, optical and electrical measurements can be made simultaneously to study the effect of electrical bias and current on molecular conformation, which may have significant impact in areas such as molecular and organic electronics.

    View details for DOI 10.1021/nl061893h

    View details for Web of Science ID 000242786500029

    View details for PubMedID 17163708

  • Soft deposition of large-area metal contacts for molecular electronics ADVANCED MATERIALS Shimizu, K. T., Fabbri, J. D., Jelincic, J. J., Melosh, N. A. 2006; 18 (12): 1499-?
  • Soft Deposition of Large Area Metal Contacts for Molecular Electronics Advanced Materials Shimizu, K., T., Fabbri, J., D., Jelincic, J., J., Melosh, N., A. 2006; 18: 1499-1504
  • Probing molecular junctions using surface plasmon resonance spectroscopy Nano Letters Shimizu, K., T., Pala, R., A., Fabbri, J., D., Brongersma, M., L., Melosh, N., A. 2006; 6: 2797-2803
  • Ultrahigh-density nanowire lattices and circuits Science Melosh, N., A., Boukai, A., Diana, F., Gerardot, B., Badolato, A., Petroff, P., M. 2003; 300: 112-15
  • Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 angstrom pores Science Zhao, D., Y., Feng, J., L., Huo, Q., S., Melosh, N., Fredrickson, G., H., Chmelka, B., F. 1998; 279: 548-552

Conference Proceedings


  • Nanostraw-Mediated Intracellular Delivery: Direct Observation of Cell/Nanotube Interfaces Xu, A. M., Aalipour, A., Melosh, N. A. CELL PRESS. 2013: 194A-194A
  • MICROFABRICATED SILICON CARBIDE THERMIONIC ENERGY CONVERTER FOR SOLAR ELECTRICITY GENERATION Lee, J. H., Bargatin, I., Gwinn, T. O., Vincent, M., Littau, K. A., Maboudian, R., Shen, Z., Melosh, N. A., Howe, R. T. IEEE. 2012
  • Engineering cell access with nano-functionalized posts Verma, P., Tayebi, N., Almquist, B., Melosh, N. AMER CHEMICAL SOC. 2011
  • Theoretical analysis of hot electron collection in metal-insulator-metal devices Wang, F., Melosh, N. A. SPIE-INT SOC OPTICAL ENGINEERING. 2011

    View details for DOI 10.1117/12.894250

    View details for Web of Science ID 000303797800011

  • Lateral fusion of lipid membranes to nanoscale functionalized Almquist, B., Melosh, N. AMER CHEMICAL SOC. 2010
  • Clathrin protein assemblies as a biotemplate VanDersarl, J. J., Melosh, N. A. AMER CHEMICAL SOC. 2010
  • AFM force spectroscopy on TAT membrane penetration Hager-Barnard, E. A., Almquist, B. D., Melosh, N. A. AMER CHEMICAL SOC. 2010
  • Fusion of Biomimetic ‘Stealth’ Probes into Lipid Bilayer Cores Almquist, B., D., Melosh, N., A. 2010
  • Influence of electrostatic fields in self assembly Melosh, N. A. AMER CHEMICAL SOC. 2009
  • An Internally Amplified Signal SOI Nano-bridge Biosensor for Electrical Detection of DNA Hybridization Parizi, K. B., Melosh, N., Nishi, Y. IEEE. 2009: 67-68
  • Suspension of nanoparticles in SU-8: Processing and characterization of nanocomposite polymers Chiamori, H. C., Brown, J. W., Adhiprakasha, E. V., Hantsoo, E. T., Straalsund, J. B., Melosh, N. A., Pruitt, B. L. ELSEVIER SCI LTD. 2008: 228-236
  • COLL 108-Lateral fusion of lipid membranes to nanoscale functionalized posts Almquist, B. D., Melosh, N. A. AMER CHEMICAL SOC. 2007
  • BIOT 53-Nanoscale reservoirs for spatially and temporally controlled biointerfaces Melosh, N. A., VanDersarl, J. J., Hagar-Barnard, E., Yenilmez, E. AMER CHEMICAL SOC. 2007
  • Silicon chip-based patch-clamp electrodes integrated with PDMS microfluidics Nagarah, J. M., Wang, P., Luo, Y., Pantoja, R., Melosh, N. A., Starace, D. M., Blunk, R., Bezanilla, F., Heath, J. R. CELL PRESS. 2005: 522A-522A

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