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1.  Nearly complete regression of tumors via collective behavior of magnetic nanoparticles in hyperthermia 
Nanotechnology  2009;20(39):395103.
One potential cancer treatment selectively deposits heat to the tumor through activation of magnetic nanoparticles inside the tumor. This can damage or kill the cancer cells without harming the surrounding healthy tissue. The properties assumed to be most important for this heat generation (saturation magnetization, amplitude and frequency of external magnetic field) originate from theoretical models that assume non-interacting nanoparticles. Although these factors certainly contribute, the fundamental assumption of ‘no interaction’ is flawed and consequently fails to anticipate their interactions with biological systems and the resulting heat deposition. Experimental evidence demonstrates that for interacting magnetite nanoparticles, determined by their spacing and anisotropy, the resulting collective behavior in the kilohertz frequency regime generates significant heat, leading to nearly complete regression of aggressive mammary tumors in mice.
doi:10.1088/0957-4484/20/39/395103
PMCID: PMC4086622  PMID: 19726837
2.  Hydrodynamic flow in the vicinity of a nanopore induced by an applied voltage 
Nanotechnology  2013;24(24):245202.
Continuum simulation is employed to study ion transport and fluid flow through a nanopore in a solid-state membrane under an applied potential drop. Results show the existence of concentration polarization layers on the surfaces of the membrane. The nonuniformity of the ionic distribution gives rise to an electric pressure that drives vortical motion in the fluid. There is also a net hydrodynamic flow through the nanopore due to an asymmetry induced by the membrane surface charge. The qualitative behavior is similar to that observed in a previous study using molecular dynamic simulations. The current–voltage characteristics show some nonlinear features but are not greatly affected by the hydrodynamic flow in the parameter regime studied. In the limit of thin Debye layers, the electric resistance of the system can be characterized using an equivalent circuit with lumped parameters. Generation of vorticity can be understood qualitatively from elementary considerations of the Maxwell stresses. However, the flow strength is a strongly nonlinear function of the applied field. Combination of electrophoretic and hydrodynamic effects can lead to ion selectivity in terms of valences and this could have some practical applications in separations.
doi:10.1088/0957-4484/24/24/245202
PMCID: PMC3738177  PMID: 23689946
3.  Multifunctional porous silicon nanopillar arrays: antireflection, superhydrophobicity, photoluminescence, and surface-enhanced Raman scattering (SERS) 
Nanotechnology  2013;24(24):245704.
We have fabricated porous silicon nanopillar arrays over large areas with a rapid, simple, and low-cost technique. The porous silicon nanopillars show unique longitudinal features along their entire length and have porosity with dimensions on the single-nanometer scale. Both Raman spectroscopy and photoluminescence data were used to determine the nanocrystallite size to be < 3 nm. The porous silicon nanopillar arrays also maintained excellent ensemble properties, reducing reflection nearly fivefold from planar silicon in the visible range without any optimization and approaching superhydrophobic behavior with increasing aspect ratio, demonstrating contact angles up to 138°. Finally, the porous silicon nanopillar arrays were made into sensitive surface enhanced Raman scattering (SERS) substrates by depositing metal onto the pillars. The SERS performance of the substrates was demonstrated using a chemical dye Rhodamine 6G. With their multitude of properties (i.e., antireflection, superhydrophobicity, photoluminescence, and sensitive SERS), the porous silicon nanopillar arrays described here can be valuable in applications such as solar harvesting, electrochemical cells, self-cleaning devices, and dynamic biological monitoring.
doi:10.1088/0957-4484/24/24/245704
PMCID: PMC3994165  PMID: 23703091
4.  Use of self-actuating and self-sensing cantilevers for imaging biological samples in fluid 
Nanotechnology  2009;20(43):434003.
In this paper, we present a detailed investigation into the suitability of atomic force microscopy (AFM) cantilevers with integrated deflection sensor and micro-actuator for imaging of soft biological samples in fluid. The Si cantilevers are actuated using a micro-heater at the bottom end of the cantilever. Sensing is achieved through p-doped resistors connected in a Wheatstone bridge. We investigated the influence of the water on the cantilever dynamics, the actuation and the sensing mechanisms, as well as the crosstalk between sensing and actuation. Successful imaging of yeast cells in water using the integrated sensor and actuator shows the potential of the combination of this actuation and sensing method. This constitutes a major step towards the automation and miniaturization required to establish AFM in routine biomedical diagnostics and in vivo applications.
doi:10.1088/0957-4484/20/43/434003
PMCID: PMC4035104  PMID: 19801750
5.  An Electro-hydrodynamics-based model for the ionic conductivity of solid-state nanopores during DNA translocation 
Nanotechnology  2013;24(19):195702.
A solid-state nanopore can be used to sense DNA (or other macromolecules) by monitoring ion-current changes that result from translocation of the molecule through the pore. When transiting a nanopore, the highly negatively charged DNA interacts with a nanopore both electrically and hydrodynamically, causing a current blockage or a current enhancement at different ion concentrations. This effect was previously characterized using a phenomenological model that can be considered as the limit of the electro-hydrodynamics model presented here. We show theoretically that the effect of surface charge of a nanopore (or electroosmotic effect) can be equivalently treated as modifications of electrophoretic mobilities of ions in the pore, providing an improved physical understanding of the current blockage (or enhancement).
doi:10.1088/0957-4484/24/19/195702
PMCID: PMC3681960  PMID: 23579206
6.  Multiplex detection of breast cancer biomarkers using plasmonic molecular sentinel nanoprobes 
Nanotechnology  2009;20(6):065101.
We have demonstrated for the first time the feasibility of multiplex detection using the surface-enhanced Raman scattering-based molecular sentinel (MS) technology in a homogeneous solution. Two MS nanoprobes tagged with different Raman labels were used to detect the presence of the erbB-2 and ki-67 breast cancer biomarkers. The multiplexing capability of the MS technique was demonstrated by mixing the two MS nanoprobes and tested in the presence of single or multiple DNA targets.
doi:10.1088/0957-4484/20/6/065101
PMCID: PMC4022306  PMID: 19417369
7.  Stimuli-responsive transformation in carbon nanotube/expanding microsphere-polymer composites 
Nanotechnology  2013;24(18):185703.
Our work introduces a class of stimuli-responsive expanding polymer composites with ability to unidirectionally transform physical dimensions, elastic modulus, density, and electrical resistance. Carbon nanotubes and core-shell acrylic microspheres were dispersed in polydimethylsiloxane, resulting in composites that exhibit a binary set of material properties. Upon thermal or infrared stimuli, liquid cores encapsulated within the microspheres vaporize, expanding the surrounding shells and stretching the matrix. Microsphere expansion results in visible dimensional changes, regions of reduced polymeric chain mobility, nanotube tensioning, and overall elastic to plastic-like transformation of the composite. Here we show composite transformations including macroscopic volume expansion (>500%), density reduction (>80%), and elastic modulus increase (>675%). Additionally, conductive nanotubes allow for remote expansion monitoring and exhibit distinct loading-dependent electrical responses. With ability to pattern regions of tailorable expansion, strength, and electrical resistance into a single polymer skin, these composites present opportunities as structural and electrical building blocks in smart systems.
doi:10.1088/0957-4484/24/18/185703
PMCID: PMC3697066  PMID: 23574648
8.  Integration of solid-state nanopores in a 0.5 μm cmos foundry process 
Nanotechnology  2013;24(15):155501.
High-bandwidth and low-noise nanopore sensor and detection electronics are crucial in achieving single-DNA base resolution. A potential way to accomplish this goal is to integrate solid-state nanopores within a CMOS platform, in close proximity to the biasing electrodes and custom-designed amplifier electronics. Here we report the integration of solid-state nanopore devices in a commercial complementary metal-oxide semiconductor (CMOS) potentiostat chip implemented in On-Semiconductor’s 0.5 μm technology. Nanopore membranes incorporating electrodes are fabricated by post-CMOS micromachining utilizing the N+ polysilicon/SiO2/N+ polysilicon capacitor structure available in the aforementioned process. Nanopores are created in the CMOS process by drilling in a transmission electron microscope and shrinking by atomic layer deposition. We also describe a batch fabrication method to process a large of number of electrode-embedded nanopores with sub-10 nm diameter across CMOS-compatible wafers by electron beam lithography and atomic layer deposition. The CMOS-compatibility of our fabrication process is verified by testing the electrical functionality of on-chip circuitry. We observe high current leakage with the CMOS nanopore devices due to the ionic diffusion through the SiO2 membrane. To prevent this leakage, we coat the membrane with Al2O3 which acts as an efficient diffusion barrier against alkali ions. The resulting nanopore devices also exhibit higher robustness and lower 1/f noise as compared to SiO2 and SiNx. Furthermore, we propose a theoretical model for our low-capacitance CMOS nanopore devices, showing good agreement with the experimental value. In addition, experiments and theoretical models of translocation studies are presented using 48.5 kbp λ-DNA in order to prove the functionality of on-chip pores coated with Al2O3.
doi:10.1088/0957-4484/24/15/155501
PMCID: PMC3672232  PMID: 23519330
9.  Silver Nanoparticle Toxicity in the Embryonic Zebrafish is Governed by Particle Dispersion and Ionic Environment 
Nanotechnology  2013;24(11):115101.
The mechanism of action of silver nanoparticles (AgNPs) is unclear due to the particles’ strong tendency to agglomerate. Preventing agglomeration could offer precise control of the physicochemical properties that drive biological response to AgNPs. In an attempt to control agglomeration, we exposed zebrafish embryos to AgNPs of 20 or 110 nm core size, and polypyrrolidone (PVP) or citrate surface coatings in media of varying ionic strength. AgNPs remained unagglomerated in 62.5 μM CaCl2 (CaCl2) and ultrapure water (UP), but not in standard zebrafish embryo medium (EM). Zebrafish embryos developed normally in the low ionic strength environments of CaCl2 and UP. Exposure of embryos to AgNPs suspended in UP and CaCl2 resulted in higher toxicity than suspensions in EM. 20 nm AgNPs were more toxic than 110 nm AgNPs, and the PVP coating was more toxic than the citrate coating at the same particle core size. The silver tissue burden correlated well with observed toxicity but only for those exposures where the AgNPs remained unagglomerated. Our results demonstrate that size- and surface coating-dependent toxicity is a result of AgNPs remaining unagglomerated, and thus a critical-design consideration for experiments to offer meaningful evaluations of AgNP toxicity.
doi:10.1088/0957-4484/24/11/115101
PMCID: PMC3782284  PMID: 23449170
10.  Upconversion in NaYF4: Yb, Er Nanoparticles Amplified by Metal Nanostructures 
Nanotechnology  2011;22(32):325604.
Upconversion (UC) fluorescence in NaYF4: Yb, Er nanoparticles amplified by metal nanostructures was compared in two nanostructure geometries: gold nanoshells surrounding nanoparticles and silver nanostructures adjacent to the nanoparticles, both placed on a dielectric silica surface. Enhanced UC luminescence signals and modified lifetimes induced by these two metals were observed in our study. The UC luminescence intensities of green and red emissions were enhanced by Ag nanostructures by a factor of approximately 4.4 and 3.5, respectively. The corresponding UC lifetimes were reduced ~1.7-fold and ~2.4-fold. In NaYF4: Yb, Er nanoparticles encapsulated in gold nanoshells, higher luminescence enhancement factors were obtained (~9.1-fold for the green emission and ~6.7-fold for the red emission). However, the Au shell coating extended the red emission by a factor of 1.5 and did not obviously change the lifetime of green emission. The responsible mechanisms such as plasmonic enhancement and surface effects are discussed.
doi:10.1088/0957-4484/22/32/325604
PMCID: PMC3962131  PMID: 21772069
11.  The structure of monomeric components of self-assembling CXCR4 antagonists determines the architecture of resulting nanostructures 
Nanotechnology  2011;22(50):505101.
Self-assembling peptides play increasingly important roles in the development of novel materials and drug delivery vehicles. Understanding mechanisms governing the assembly of nanoarchitectures is essential for the generation of peptide-based nanodevices. We find that a cone-shaped derivative of the second transmembrane domain of CXCR4 receptor, x4-2-6 self-assembles into nanospheres, while a related cylindrical peptide, x4-2-9 forms fibrils. Stronger intermolecular interactions in nanospheres than in fibrils result in slow rates of particle disassembly and protection against proteolytic degradation.
doi:10.1088/0957-4484/22/50/505101
PMCID: PMC3950977  PMID: 22107755
12.  Nanoscale Protein Arrays of Rich Morphologies via Self-assembly on Chemically Treated Diblock Copolymer Surfaces 
Nanotechnology  2013;24(9):095601.
Well-controlled assembly of proteins on supramolecular templates of block copolymers can be extremely useful for high-throughput biodetection. We report the adsorption and assembly characteristics of a model antibody protein to various polystyrene-block-poly(4-vinylpyridine) templates whose distinctive nanoscale structures are obtained through time-regulated exposure to chloroform vapor. Strong adsorption preference of the protein to the polystyrene segment in the diblock copolymer templates leads to an easily predictable, controllable, rich set of nanoscale protein morphologies through self-assembly. We also demonstrate that the chemical identities of various subareas within individual nanostructures can be readily elucidated by investigating the corresponding protein adsorption behavior to each chemically distinct area of the template. In our approach, a rich set of intricate nanoscale morphologies of protein arrays that cannot be easily attained through other means can be generated straightforwardly via self-assembly of proteins on chemically treated diblock copolymer surfaces, without the use of clean room-based fabrication tools. Our approach provides much-needed flexibility and versatility for the use of block copolymer-based protein arrays in biodetection. The ease of fabrication in producing well-defined and self-assembled templates can contribute to a high degree of versatility and simplicity in acquiring intricate nanoscale geometry and spatial distribution of proteins in arrays. These advantages can be extremely beneficial both for fundamental research and biomedical detection, especially in the areas of solid-state based, high-throughput protein sensing.
doi:10.1088/0957-4484/24/9/095601
PMCID: PMC3600641  PMID: 23395956
protein assembly; protein adsorption; protein array; diblock copolymer; polymeric nanotemplate
13.  Template synthesis of test tube nanoparticles using non-destructive replication 
Nanotechnology  2013;24(8):085601.
Nano test tubes are a promising delivery vehicle for a range of therapeutics including small molecule drugs and biologics. However, current template synthesis methods of producing nano test tubes are prohibitively expensive and time consuming. Here, non-destructive template replication was used to increase nano test tube yield from porous alumina by more than a hundredfold. We demonstrate how to produce nano test tubes of several sizes and compositions including hybrid tubes with different inner and outer surfaces for targeted surface chemistry. Nano test tubes were readily suspended and stored in aqueous solutions without the need for chemical treatment. These nano test tubes should find application as delivery vehicles for therapeutics, particularly for processive “bionanoreactors” loaded with enzymes.
doi:10.1088/0957-4484/24/8/085601
PMCID: PMC3689541  PMID: 23376956
14.  Growth of textured thin Au coatings on iron oxide nanoparticles with near infrared absorbance 
Nanotechnology  2012;24(2):025606.
A homologous series of Au-coated iron oxide nanoparticles, with hydrodynamic diameters smaller than 60 nm was synthesized with very low Auto-iron mass ratios as low as 0.15. The hydrodynamic diameter was determined by dynamic light scattering and the composition by atomic absorption spectroscopy and energy dispersive x-ray spectroscopy (EDS). Unusually low Au precursor supersaturation levels were utilized to nucleate and grow Au coatings on iron oxide relative to formation of pure Au nanoparticles. This approach produced unusually thin coatings, by lowering autocatalytic growth of Au on Au, as shown by transmission electron microscopy (TEM). Nearly all of the nanoparticles were attracted by a magnet indicating a minimal amount of pure Au particles The coatings were sufficiently thin to shift the surface plasmon resonance (SPR) to the near infrared (NIR), with large extinction coefficients., despite the small particle hydrodynamic diameters, observed from dynamic light scattering to be less than 60 nm.
doi:10.1088/0957-4484/24/2/025606
PMCID: PMC3893819  PMID: 23238021
15.  LOAD TRANSFER AND MECHANICAL PROPERTIES OF CHEMICALLY DERIVED SINGLE LAYER GRAPHENE REINFORCEMENTS IN POLYMER COMPOSITES 
Nanotechnology  2012;23(50):505713.
We report load transfer and mechanical properties of chemically derived single layer graphene (SLG) as reinforcements in poly (dimethyl) siloxane (PDMS) composites. Mixing single layer graphene in polymers resulted in the marked decrease of the G’ or 2D band intensity due to doping and functionalization. A Raman G mode shift of 11.2 cm−1/% strain in compression and 4.2 cm−1/% strain in tension is reported. An increase in elastic modulus of PDMS by ~42%, toughness by ~39%, damping capability by ~673%, and strain energy density of ~43% by the addition of 1 wt. % SLG in PDMS is reported.
doi:10.1088/0957-4484/23/50/505713
PMCID: PMC3697060  PMID: 23196792
16.  Nanomechanical detection of cholera toxin using microcantilevers functionalized with ganglioside nanodiscs 
Nanotechnology  2010;21(43):10.1088/0957-4484/21/43/435502.
The label-free detection of cholera toxin is demonstrated using microcantilevers functionalized with ganglioside nanodiscs. The cholera toxin molecules bind specifically to the active membrane protein encased in nanodiscs, nanoscale lipid bilayers surrounded by an amphipathic protein belt, immobilized on the cantilever surface. The specific molecular binding results in cantilever deflection via the formation of a surface stress-induced bending moment. The nanomechanical cantilever response is quantitatively monitored by optical interference. The consistent and reproducible nanomechanical detection of cholera toxin in nanomolar range concentrations is demonstrated. The results validated with such a model system suggest that the combination of a microcantilever platform with receptor nanodiscs is a promising approach for monitoring invasive pathogens and other types of biomolecular detection relevant to drug discovery.
doi:10.1088/0957-4484/21/43/435502
PMCID: PMC3868204  PMID: 20890017
17.  DNA Translocating Through a Carbon Nanotube Can Increase Ionic Current 
Nanotechnology  2012;23(45):455107.
DNA translocation through a narrow, single-walled carbon nanotube can be accompanied by large increases of ion current, recently observed in contrast to the ion current blockade. We use molecular dynamics simulations to show large electro-osmotic flow can be turned into a large net current via ion-selective filtering by a DNA molecule inside the carbon nanotube.
doi:10.1088/0957-4484/23/45/455107
PMCID: PMC3508069  PMID: 23090315
18.  Mass transport through vertically aligned large diameter MWCNT embedded in parylene 
Nanotechnology  2012;23(45):455101.
We have fabricated porous membranes using a parylene encapsulated vertically aligned forest of multi-walled carbon nanotube (MWCNT, about 7nm inner diameter). The transport of charged particles in electrolyte through these membranes was studied by applying electric field and pressure. Under an electric field in the range of 4.4×104 V/m, electrophoresis instead of electroomosis is found to be the main mechanism for ion transport. Small molecules and 5 nm gold nanoparticles can be driven through the membranes by an electric field. However, small biomolecules, like DNA oligomers, cannot. Due to the weak electric driving force, the interactions between charged particles and the hydrophobic CNT inner surface play important roles in the transport, leading to enhanced selectivity for small molecules. Simple chemical modification on the CNT ends also induces an obvious effect on the translocation of single strand DNA oligomer and gold nanoparticle under a modest pressure (<294 Pa).
doi:10.1088/0957-4484/23/45/455101
PMCID: PMC3563677  PMID: 23064678
nanofluidics; nanopore; nanochannel; vertical aligned carbon nanotube forest; parylene thin film
19.  On the Role of low-energy electrons in the radiosensitization of DNA by gold nanoparticles 
Nanotechnology  2011;22(46):10.1088/0957-4484/22/46/465101.
Four different gold nanoparticle (GNP) preparations, including nude GNP and GNP coated either with thiolated undecane (S-C11H23), or with dithiolated diethylenetriaminepentaacetic (DTDTPA) or gadolinium (Gd) DTDTPA chelating agents were synthesized. The average diameters, for each type of nanoparticle are 5 nm, 10 and 13 nm, respectively. Dry films of plasmid DNA pGEM-3Zf(-), DNA with bound GNP and DNA with coated GNP were bombarded with 60 keV electrons. The yields of single and double strand breaks were measured as a function of exposure by electrophoresis. The binding of only one GNP without coating to DNA containing 3197 base pairs increases single and double strand breaks by a factor of 2.3 while for GNP coated with S-C11H23 this factor is reduced to 1.6. GNP coated with the DTDTPA and DTDTPA:Gd in same ratio with DNA, produce essentially no increment in damage. These results could be explained by the attenuation by the coatings of the intensity of low energy photoelectrons emitted from GNP. Thus, coatings of GNP may considerably attenuate short-range low energy electrons emitted from gold, leading to a considerable decrease of radiosensitization. According to our results, the highest radiosensitization should be obtained with GNP having the shortest possible ligand, directed to the DNA of cancer cells.
doi:10.1088/0957-4484/22/46/465101
PMCID: PMC3829822  PMID: 22024607 CAMSID: cams1998
20.  Automated Dispersion and Orientation Analysis for Carbon Nanotube Reinforced Polymer Composites 
Nanotechnology  2012;23(43):435706.
The properties of carbon nanotube (CNT)/polymer composites are strongly dependent on the dispersion and orientation of CNTs in the host matrix. Quantification of the dispersion and orientation of CNTs by microstructure observation and image analysis has been demonstrated as a useful way to understand the structure-property relationship of CNT/polymer composites. However, due to the various morphologies and large amount of CNTs in one image, automatic and accurate identification of CNTs has become the bottleneck for dispersion/orientation analysis. To solve this problem, shape identification is performed for each pixel in the filler identification step, so that individual CNT can be exacted from images automatically. The improved filler identification enables more accurate analysis of CNT dispersion and orientation. The obtained dispersion index and orientation index of both synthetic and real images from model compounds correspond well with the observations. Moreover, these indices help to explain the electrical properties of CNT/Silicone composite, which is used as a model compound. This method can also be extended to other polymer composites with high aspect ratio fillers.
doi:10.1088/0957-4484/23/43/435706
PMCID: PMC3492886  PMID: 23060008
21.  Palladium Electrodes for Molecular Tunnel Junctions 
Nanotechnology  2012;23(42):425202.
Gold has been the metal of choice for research on molecular tunneling junctions, but it is incompatible with CMOS fabrication because it forms deep level traps in silicon. Palladium electrodes do not contaminate silicon, and also give higher tunnel current signals in the molecular tunnel junctions we have studied. The result is cleaner signals in a recognition-tunneling junction that recognizes the four natural DNA bases as well as 5-methyl cytosine, with no spurious background signals. More than 75% of all the recorded signal peaks call the base correctly.
doi:10.1088/0957-4484/23/42/425202
PMCID: PMC3501205  PMID: 23037952
22.  Ion transport through a graphene nanopore 
Nanotechnology  2012;23(39):395501.
Molecular dynamics simulation is utilized to investigate the ionic transport of NaCl in solution through a graphene nanopore under an applied electric field. Results show the formation of concentration polarization layers in the vicinity of the graphene sheet. The nonuniformity of the ion distribution gives rise to an electric pressure which drives vortical motions in the fluid if the electric field is sufficiently strong to overcome the influence of viscosity and thermal fluctuations. The relative importance of hydrodynamic transport and thermal fluctuations in determining the pore conductivity is investigated. A second important effect that is observed is the mass transport of water through the nanopore, with an average velocity proportional to the applied voltage and independent of the pore diameter. The flux arises as a consequence of the asymmetry in the ion distribution which can be attributed to differing mobilities of the sodium and chlorine ions, and, to the polarity of water molecules. The accumulation of liquid molecules in the vicinity of the nanopore due to reorientation of the water dipoles by the local electric field is seen to result in a local increase in the liquid density. Results confirm that the electric conductance is proportional to the nanopore diameter for the parameter regimes that we simulated. The occurrence of fluid vortices is found to result in an increase in the effective electrical conductance.
doi:10.1088/0957-4484/23/39/395501
PMCID: PMC3446844  PMID: 22962262
23.  Simultaneous quantification of multiple magnetic nanoparticles 
Nanotechnology  2010;21(45):455101.
Distinct magnetic nanoparticle designs can have unique spectral responses to an AC magnetic field in a technique called the magnetic spectroscopy of Brownian motion (MSB). The spectra of the particles have been measured using desktop spectrometers and in vivo measurements. If multiple particle types are present in a region of interest, the unique spectral signatures allow for the simultaneous quantification of the various particles. We demonstrate such a potential experimentally with up to three particle types. This ability to concurrently detect multiple particles will enable new biomedical applications.
doi:10.1088/0957-4484/21/45/455101
PMCID: PMC3786441  PMID: 20947953
24.  Selective Filling of Nanowells in Nanowell Arrays Fabricated Using Polystyrene Nanosphere Lithography with Cytochrome P450 Enzymes 
Nanotechnology  2012;23(38):385101.
This work describes an original and simple technique for protein immobilization into nanowells, fabricated using nanopatterned-array fabrication methods, while ensuring the protein retains the normal biological activity. Nanosphere-lithography was used to fabricate a nanowell array with nanowells that were 100 nm in diameter and a periodicity of 500 nm. The base of the nanowells was gold and the surrounding material was silicon dioxide. The different surface chemistries of these materials were used to attach two different self-assembled monolayers (SAM) with different affinities for the protein used here, cytochrome P450 (P450). The nanowell SAM, a methyl terminated thiol, had high affinity for the P450. The surrounding SAM, a polyethylene glycol silane, displayed very little affinity toward the P450 isozyme CYP2C9, as demonstrated by x-ray photoelectron spectroscopy and surface plasmon resonance. The regularity of the nanopatterned array was examined by scanning electron microscopy and atomic force microscopy. P450-mediated metabolism experiments of known substrates demonstrated that the nanowell bound P450 enzyme exceeded its normal activity, as compared to P450 solutions, when bound to the methyl terminated self-assembled monolayer. The nanopatterned array chips bearing P450 display long term stability and give reproducible results making them potentially useful for high throughput screening assays or as nanoelectrode arrays.
doi:10.1088/0957-4484/23/38/385101
PMCID: PMC3465080  PMID: 22947619
Nanowell array; Self-assembled monolayer; cytochrome P450
25.  Fabrication and Characterization of Solid-state Nanopore Arrays for High Throughput DNA Sequencing 
Nanotechnology  2012;23(38):385308.
We report the fabrication and characterization of uniformly-sized nanopore arrays, integrated into an optical detection system for high-throughput DNA sequencing applications. Nanopore arrays were fabricated using Focused Ion Beam milling followed by TiO2 coating using Atomic Layer Deposition (ALD). The TiO2 layer decreases the initial pore diameter down to sub-10nm range, compatible with the requirements for nanopore-based sequencing using optical readout. We find that the TiO2 layers produce a lower photoluminescence background as compared with the more broadly used Al2O3 coatings. The functionality of the nanopore array was demonstrated by the simultaneous optical detection of DNA-quantum dot-conjugates, which were electro-kinetically driven through the nanopores. Our optical scheme employs Total Internal Reflection Fluorescence (TIRF) microscopy to illuminate a wide area of the TiO2-coated membrane. A highly parallel system for observing DNA capture events in a uniformly-sized 6×6 nanopore array was experimentally realized.
doi:10.1088/0957-4484/23/38/385308
PMCID: PMC3557807  PMID: 22948520

Results 1-25 (109)