Publications
86 results found
Paulose Nadappuram B, Cadinu P, Barik A, et al., 2019, Nanoscale tweezers for single-cell biopsies, Nature Nanotechnology, Vol: 14, Pages: 80-88, ISSN: 1748-3387
Much of the functionality of multicellular systems arises from the spatial organization and dynamic behaviours within and between cells. Current single-cell genomic methods only provide a transcriptional ‘snapshot’ of individual cells. The real-time analysis and perturbation of living cells would generate a step change in single-cell analysis. Here we describe minimally invasive nanotweezers that can be spatially controlled to extract samples from living cells with single-molecule precision. They consist of two closely spaced electrodes with gaps as small as 10–20 nm, which can be used for the dielectrophoretic trapping of DNA and proteins. Aside from trapping single molecules, we also extract nucleic acids for gene expression analysis from living cells without affecting their viability. Finally, we report on the trapping and extraction of a single mitochondrion. This work bridges the gap between single-molecule/organelle manipulation and cell biology and can ultimately enable a better understanding of living cells.
Xue L, Cadinu P, Paulose Nadappuram B, et al., 2018, Gated single-molecule transport in double-barreled nanopores, ACS Applied Materials and Interfaces, Vol: 10, Pages: 38621-38629, ISSN: 1944-8244
Single-molecule methods have been rapidly developing with the appealing prospect of transforming conventional ensemble-averaged analytical techniques. However, challenges remain especially in improving detection sensitivity and controlling molecular transport. In this article, we present a direct method for the fabrication of analytical sensors that combine the advantages of nanopores and field-effect transistors for simultaneous label-free single-molecule detection and manipulation. We show that these hybrid sensors have perfectly aligned nanopores and field-effect transistor components making it possible to detect molecular events with up to near 100% synchronization. Furthermore, we show that the transport across the nanopore can be voltage-gated to switch on/off translocations in real time. Finally, surface functionalization of the gate electrode can also be used to fine tune transport properties enabling more active control over the translocation velocity and capture rates.
Al Sulaiman D, Cadinu P, Ivanov AP, et al., 2018, Chemically modified hydrogel-filled nanopores: a tunable platform for single-molecule sensing, Nano Letters: a journal dedicated to nanoscience and nanotechnology, Vol: 18, Pages: 6084-6093, ISSN: 1530-6984
Label-free, single-molecule sensing is an ideal candidate for biomedical applications that rely on the detection of low copy numbers in small volumes and potentially complex biofluids. Among them, solid-state nanopores can be engineered to detect single molecules of charged analytes when they are electrically driven through the nanometer-sized aperture. When successfully applied to nucleic acid sensing, fast transport in the range of 10–100 nucleotides per nanosecond often precludes the use of standard nanopores for the detection of the smallest fragments. Herein, hydrogel-filled nanopores (HFN) are reported that combine quartz nanopipettes with biocompatible chemical poly(vinyl) alcohol hydrogels engineered in-house. Hydrogels were modified physically or chemically to finely tune, in a predictable manner, the transport of specific molecules. Controlling the hydrogel mesh size and chemical composition allowed us to slow DNA transport by 4 orders of magnitude and to detect fragments as small as 100 base pairs (bp) with nanopores larger than 20 nm at an ionic strength comparable to physiological conditions. Considering the emergence of cell-free nucleic acids as blood biomarkers for cancer diagnostics or prenatal testing, the successful sensing and size profiling of DNA fragments ranging from 100 bp to >1 kbp long under physiological conditions demonstrates the potential of HFNs as a new generation of powerful and easily tunable molecular diagnostics tools.
Ivanov AP, Edel JB, 2018, Scissoring genes with light, NATURE CHEMISTRY, Vol: 10, Pages: 800-801, ISSN: 1755-4330
Cadinu P, Campolo G, Pud S, et al., 2018, Double barrel nanopores as a new tool for controlling single-molecule transport, Nano Letters, Vol: 18, Pages: 2738-2745, ISSN: 1530-6984
The ability to control the motion of single biomolecules is key to improving a wide range of biophysical and diagnostic applications. Solid-state nanopores are a promising tool capable of solving this task. However, molecular control and the possibility of slow readouts of long polymer molecules are still limited due to fast analyte transport and low signal-to-noise ratios. Here, we report on a novel approach of actively controlling analyte transport by using a double-nanopore architecture where two nanopores are separated by only a ∼ 20 nm gap. The nanopores can be addressed individually, allowing for two unique modes of operation: (i) pore-to-pore transfer, which can be controlled at near 100% efficiency, and (ii) DNA molecules bridging between the two nanopores, which enables detection with an enhanced temporal resolution (e.g., an increase of more than 2 orders of magnitude in the dwell time) without compromising the signal quality. The simplicity of fabrication and operation of the double-barrel architecture opens a wide range of applications for high-resolution readout of biological molecules.
Peveler WJ, Noimark S, Al-Azawi H, et al., 2018, Covalently attached antimicrobial surfaces using BODIPY: improving efficiency and effectiveness, ACS Applied Materials and Interfaces, Vol: 10, Pages: 98-104, ISSN: 1944-8244
The development of photoactivated antimicrobial surfaces that kill pathogens through the production of singlet oxygen has proved very effective in recent years, with applications in medical devices and hospital touch surfaces, to improve patient safety and well being. However, many of these surfaces require a swell-encapsulation-shrink strategy to incorporate the photoactive agents in a polymer matrix, and this is resource intensive, given that only the surface fraction of the agent is active against bacteria. Furthermore, there is a risk that the agent will leach from the polymer and thus raises issues of biocompatibility and patient safety. Here, we describe a more efficient method of fabricating a silicone material with a covalently attached monolayer of photoactivating agent that uses heavy-atom triplet sensitization for improved singlet oxygen generation and corresponding antimicrobial activity. We use boron-dipyrromethane with a reactive end group and incorporated Br atoms, covalently attached to poly(dimethylsiloxane). We demonstrate the efficacy of this material in producing singlet oxygen and killing Staphylococcus aureus and suggest how it might be easily modifiable for future antimicrobial surface development.
Kunstmann-Olsen C, 2018, Joshua Edel, Aleksandar Ivanov, and MinJun Kim (Eds): Nanofluidics, 2nd Edn, Chromatographia, Vol: 81, Pages: 173-173, ISSN: 0009-5893
Sze JYY, Ivanov AP, Cass AEG, et al., 2017, Single molecule multiplexed nanopore protein screening in human serum using aptamer modified DNA carriers, Nature Communications, Vol: 8, Pages: 1-10, ISSN: 2041-1723
The capability to screen a range of proteins at the single-molecule level with enhanced selectivity in biological fluids has been in part a driving force in developing future diagnostic and therapeutic strategies. The combination of nanopore sensing and nucleic acid aptamer recognition comes close to this ideal due to the ease of multiplexing, without the need for expensive labelling methods or extensive sample pre-treatment. Here, we demonstrate a fully flexible, scalable and low-cost detection platform to sense multiple protein targets simultaneously by grafting specific sequences along the backbone of a double-stranded DNA carrier. Protein bound to the aptamer produces unique ionic current signatures which facilitates accurate target recognition. This powerful approach allows us to differentiate individual protein sizes via characteristic changes in the sub-peak current. Furthermore, we show that by using DNA carriers it is possible to perform single-molecule screening in human serum at ultra-low protein concentrations.
Crick CR, Albella P, Kim H-J, et al., 2017, Low-Noise Plasmonic Nanopore Biosensors for Single Molecule Detection at Elevated Temperatures, ACS Photonics, Vol: 4, Pages: 2835-2842, ISSN: 2330-4022
Advanced single molecular analysis is a key stepping stone for the rapid sensing and characterization of biomolecules. This will only be made possible through the implementation of versatile platforms, with high sensitivities and the precise control of experimental conditions. The presented work details an advancement of this technology, through the development of a low-noise Pyrex/silicon nitride/gold nanopore platform. The nanopore is surrounded by a plasmonic bullseye structure and provides targeted and controllable heating via laser irradiation, which is directed toward the center of the pore. The device architecture is investigated using multiwavelength laser heating experiments and 'individual DNA molecules are detected under controlled heating. The plasmonic features, optimized through numerical simulations, are tuned to the wavelength of incident light, ensuring a platform that provides substantial heating with high signal-to-noise.
Ren R, Zhang Y, Paulose Nadappuram B, et al., 2017, Nanopore extended field effect transistor for selective single molecule biosensing, Nature Communications, Vol: 8, Pages: 1-9, ISSN: 2041-1723
There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry. We report on a polypyrrole functionalized nexFET, with controllable gate voltage that can be used to switch on/off, and slow down single-molecule DNA transport through a nanopore. This strategy enables higher molecular throughput, enhanced signal-to-noise, and even heightened selectivity via functionalization with an embedded receptor. This is shown for selective sensing of an anti-insulin antibody in the presence of its IgG isotype.
Cadinu P, Paulose Nadappuram B, Lee DJ, et al., 2017, Single molecule trapping and sensing using dual nanopores separated by a zeptoliter nanobridge, Nano Letters, Vol: 17, Pages: 6376-6384, ISSN: 1530-6984
There is a growing realization, especially within the diagnostic and therapeutic community, that the amount of information enclosed in a single molecule can not only enable a better understanding of biophysical pathways, but also offer exceptional value for early stage biomarker detection of disease onset. To this end, numerous single molecule strategies have been proposed, and in terms of label-free routes, nanopore sensing has emerged as one of the most promising methods. However, being able to finely control molecular transport in terms of transport rate, resolution, and signal-to-noise ratio (SNR) is essential to take full advantage of the technology benefits. Here we propose a novel solution to these challenges based on a method that allows biomolecules to be individually confined into a zeptoliter nanoscale droplet bridging two adjacent nanopores (nanobridge) with a 20 nm separation. Molecules that undergo confinement in the nanobridge are slowed down by up to 3 orders of magnitude compared to conventional nanopores. This leads to a dramatic improvement in the SNR, resolution, sensitivity, and limit of detection. The strategy implemented is universal and as highlighted in this manuscript can be used for the detection of dsDNA, RNA, ssDNA, and proteins.
Lin X, Ivanov AP, Edel JB, 2017, Selective single molecule nanopore sensing of proteins using DNA aptamer-functionalised gold nanoparticles, Chemical Science, Vol: 8, Pages: 3905-3912, ISSN: 2041-6539
Single molecule detection methods, such as nanopore sensors have found increasing importance in applications ranging from gaining a better understanding of biophysical processes to technology driven solutions such as DNA sequencing. However, challenges remain especially in relation to improving selectivity to probe specific targets or to alternatively enable detection of smaller molecules such as small-sized proteins with a sufficiently high signal-to-noise ratio. In this article, we propose a solution to these technological challenges by using DNA aptamer-modified gold nanoparticles (AuNPs) that act as a molecular carrier through the nanopore sensor. We show that this approach offers numerous advantages including: high levels of selectivity, efficient capture from a complex mixture, enhanced signal, minimized analyte-sensor surface interactions, and finally can be used to enhance the event detection rate. This is demonstrated by incorporating a lysozyme binding aptamer to a 5 nm AuNP carrier to selectively probe lysozyme within a cocktail of proteins. We show that nanopores can reveal sub-complex molecular information, by discriminating the AuNP from the protein analyte, indicating the potential use of this technology for single molecule analysis of different molecular analytes specifically bound to AuNP.
Pitchford WH, Crick CR, Kim H-J, et al., 2017, Low Noise Nanopore Platforms Optimised for the Synchronised Optical and Electrical Detection of Biomolecules, NANOFLUIDICS, 2ND EDITION, Editors: Edel, Ivanov, Kim, Publisher: ROYAL SOC CHEMISTRY, Pages: 270-300, ISBN: 978-1-84973-404-2
, 2016, Nanofluidics, Publisher: The Royal Society of Chemistry, ISBN: 9781849734042
<jats:p>There has been significant growth in the field of nanofluidics, where nanoscale analytical instruments employ micromachined features and are able to manipulate fluid samples with high precision and efficiency and have many advantages over their conventional (larger) analogues.</jats:p> <jats:p>The new edition of Nanofluidics has been fully revised and updated with the latest advancements and applications. With a focus on bioanalysis, specific applications are given with case studies. The end of each chapter now also features a methodology section to explain experimental protocols and “tips and tricks”.</jats:p> <jats:p>The editors draw on an international authorship and provide a handbook for the community. Written at an accessible level the book is suitable for both experts and non-experts alike.</jats:p>
Edel J, Ivanov A, Kim M, 2016, Nanofluidics (Second Edition), Publisher: Royal Society of Chemistry, ISBN: 9781849734042
Despite the growth of this field, there are surprisingly few books dedicated to nanofluidics. This book will fill the gap in the literature for a text focusing on bioanalytical applications.
Crick CR, Noimark S, Peveler WJ, et al., 2016, Advanced Compositional Analysis of Nanoparticle-polymer Composites Using Direct Fluorescence Imaging, Jove-Journal of Visualized Experiments, Vol: 113, ISSN: 1940-087X
The fabrication of polymer-nanoparticle composites is extremely important in the development of many functional materials. Identifying the precise composition of these materials is essential, especially in the design of surface catalysts, where the surface concentration of the active component determines the activity of the material. Antimicrobial materials which utilize nanoparticles are a particular focus of this technology. Recently swell encapsulation has emerged as a technique for inserting antimicrobial nanoparticles into a host polymer matrix. Swell encapsulation provides the advantage of localizing the incorporation to the external surfaces of materials, which act as the active sites of these materials. However, quantification of this nanoparticle uptake is challenging. Previous studies explore the link between antimicrobial activity and surface concentration of the active component, but this is not directly visualized. Here we show a reliable method to monitor the incorporation of nanoparticles into a polymer host matrix via swell encapsulation. We show that the surface concentration of CdSe/ZnS nanoparticles can be accurately visualized through cross-sectional fluorescence imaging. Using this method, we can quantify the uptake of nanoparticles via swell encapsulation and measure the surface concentration of encapsulated particles, which is key in optimizing the activity of functional materials.
Freedman KJ, Crick CR, Albella P, et al., 2016, On-Demand Surface and Tip Enhanced Raman Spectroscopy Using Dielectrophoretic Trapping and Nanopore Sensing, ACS Photonics, Vol: 3, Pages: 1036-1044, ISSN: 2330-4022
Surface enhanced Raman spectroscopy (SERS) and tip-enhanced Raman Spectroscopy (TERS) have shown great promise in the detection and analysis of trace analytes throughout numerous fields of study. Both SERS and TERS utilize nanoscale plasmonic surface features to increase the intensity of observed Raman signals by many orders of magnitude (> 108). One of the major factors limiting the wider and more routine implementation of the enhanced Raman phenomena, is in the difficulty of forming consistent and reliable plasmonic substrates with well defined “hot-spots”. We address this limitation by designing a platform which can be used for both SERS and TERS respectively. The presented technique allows for rapid, controlled, “on-demand”, and reversible formation of a SERS substrate using dielectrophorisis (DEP) at the end of a nanoscale pipette. This drives gold nanoparticles in solution to concentrate and self-assemble at the tip of the pipette, where analytes can be detected effectively using SERS. An additional benefit of the platform is that the nanopipette containing a nanopore can be used for detection of individual nanoparticles facilitated by the added enhancement originating from the nanopipette tip enhanced signal. Complementing the experimental results are simulations highlighting the mechanism for SERS substrate formation and TERS detection.
Edel JB, Freedman K, Otto L, et al., 2016, Nanopore sensing at ultra-low concentrations using single molecule dielectrophoretic trapping, Nature Communications, Vol: 7, Pages: 1-9, ISSN: 2041-1723
Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data. One exceptionally promising route is in the use of nanopore sensors. However, a well-known complexity is that detection and capture is predominantly diffusion limited. This problem is compounded when taking into account the capture volume of a nanopore, typically 108–1010 times smaller than the sample volume. To rectify this disproportionate ratio, we demonstrate a simple, yet powerful, method based on coupling single-molecule dielectrophoretic trapping to nanopore sensing. We show that DNA can be captured from a controllable, but typically much larger, volume and concentrated at the tip of a metallic nanopore. This enables the detection of single molecules at concentrations as low as 5 fM, which is approximately a 103 reduction in the limit of detection compared with existing methods, while still maintaining efficient throughput.
Turek VA, Francescato Y, Cadinu P, et al., 2015, Self-Assembled Spherical Supercluster Metamaterials from Nanoscale Building Blocks, ACS Photonics, Vol: 3, Pages: 35-42, ISSN: 2330-4022
We report on a simple, universal and large scale self-assembly method for generation of spherical superclusters from nanoscopic building blocks. The fundamentals of this approach relies on the ultra-high pre-concentration of nanoparticles (NP) followed by either using emulsification strategies or alternatively multiphase microfluidic microdroplets. In both cases drying of the NP droplets yield highly spherical self-assembled superclusters with unique optical properties. We demonstrate that the behaviour of these spheres can be controlled by surface functionalization before and after the self-assembly process. These structures show unique plasmonic collective response both on the surface and within the supercluster in the visible and infrared regions. Furthermore, we demonstrate that these strong, tunable optical modes can be used towards ultra-sensitive, reproducible, surface-enhanced spectroscopies.
Daeubler M, Ivanov A, Sjenitzer BL, et al., 2015, High-fidelity coupled Monte Carlo neutron transport and thermal-hydraulic simulations using Serpent 2/SUBCHANFLOW, Annals of Nuclear Energy, Vol: 83, Pages: 352-375, ISSN: 0306-4549
Abstract Efforts to develop high-fidelity, in silico or ab initio, high performance multi-physics tools are undertaken by many groups due to the availability of relatively cheap, large-scale parallel computers. To this end, an internal coupling between the Monte Carlo reactor physics code Serpent 2 and the sub-channel code SUBCHANFLOW has been developed. The coupled code system is intended to serve as reference for deterministic reactor dynamics code developments in the future. It exploits the fact that Serpent was conceived as a lattice code for such deterministic tools. The coupling utilizes Serpent's recently introduced universal multi-physics interface. With the multi-physics interface enabled, Serpent treats temperature dependence of nuclear data using the target motion sampling method. Since the target motion sampling methodology cannot be applied to thermal bound-atom scattering or unresolved resonances, a stochastic mixing fall back algorithm to enable the simulation of thermal reactors has been implemented. The developed coupled code is verified by code-to-code comparison with an external coupling of the Monte Carlo tool TRIPOLI4 and SUBCHANFLOW as well as the internally coupled code MCNP5/SUBCHANFLOW. Simulation results of all code systems were found to be in good agreement. Thereafter, the second exercise of the OECD/NEA and U.S. NRC PWR MOX/UO2 core transient benchmark is studied to demonstrate that Serpent 2/SUBCHANFLOW may be employed to analyze realistic, industry-like cases such as a full PWR core under hot full power conditions in a reasonable amount of time. The obtained simulation results are compared to known benchmark solutions and the numerical performance of Serpent 2/SUBCHANFLOW is analyzed to assess the feasibility of routine application. While Serpent 2/SUBCHANFLOW's performance in terms of physics and numerical efficiency is found to be generally satisfactory, options to further improve the coupled tool concerning both aspects are discusse
Ivanov A, Sanchez V, Stieglitz R, et al., 2015, Large-scale Monte Carlo neutron transport calculations with thermal hydraulic feedback, Annals of Nuclear Energy, Vol: 84, Pages: 204-219, ISSN: 0306-4549
The Monte Carlo method provides the most accurate description of the particle transport problem. The criticality problem is simulated by following the histories of individual particles without approximating the energy, angle or the coordinate dependence. These calculations are usually done using homogeneous thermal hydraulic conditions. This is a very crude approximation in the general case. In this paper, the method of internal coupling between neutron transport and thermal hydraulics is presented. The method is based on dynamic material distribution, where coordinate dependent temperature and density information is supplied on the fly during the transport calculation. This method does not suffer from the deficiencies characteristic of the external coupling via the input files. In latter case, the geometry is split into multiple cells having distinct temperatures and densities to supply the feedback. The possibility to efficiently simulate large scale geometries at pin-by-pin and subchannel level resolution was investigated. The Wielandt shift method for reducing the dominance ratio of the system and accelerating the fission source convergence was implemented. During the coupled iteration a detailed distribution of the fission heat deposition is required by the thermal hydraulics calculation. Providing reasonable statistical uncertainties for tallies having large numbers of bins, is a complicated task. This problem was resolved by applying the Uniform Fission Site method. Previous investigations showed that the convergence of the coupled neutron transport/thermal hydraulics calculation is limited by the statistical uncertainty and exhibits strong nonuniform behavior. The stochastic approximation scheme was used to stabilize the convergence. In combination with the Uniform Fission Site method, uniform convergence was achieved.
Crick CR, Noimark S, Peveler WJ, et al., 2015, Advanced analysis of nanoparticle composites – A neans toward increasing the efficiency of functional materials, RSC Advances, Vol: 5, Pages: 53789-53795, ISSN: 2046-2069
The applications of functional materials containing nanoparticles are rapidly increasing. This area is especially relevant to the healthcare industry and the design of new light activated antimicrobials. Wider application of these materials will require quantification of localised nanoparticle concentration, which is currently only available through indirect estimates (including functional testing and bulk spectroscopy). The work presented uses direct visualisation of embedded cadmium selenide quantum dots (Ø - 13.1 nm) using fluorescence lifetime imaging. The nanoparticles used in this study are embedded into a polydimethylsiloxane host matrix via swell encapsulation. The swell encapsulation of the particles is shown to achieve the highest concentration of material at the polymers surface, while a lower concentration is found in the bulk. Fluorescence imaging provides direct comparison of nanoparticle concentration between samples. A comparative swell encapsulation of titanium dioxide nanoparticles (Ø - 12.6 nm) provides further analysis, including photocatalytic dye degradation, water contact angle measurement and energy-dispersive X-ray analysis. The techniques demonstrated allow quantification of nanoparticle concentration within a host matrix, both the functional nanoparticles at the materials’ surface and the redundant particles within the bulk.
Sze JYY, Kumar S, Ivanov AP, et al., 2015, Fine tuning of nanopipettes using atomic layer deposition for single molecule sensing, Analyst, Vol: 14, Pages: 4828-4834, ISSN: 0003-2654
Nanopipettes are an attractive single-molecule tool for identification and characterisation of nucleic acids and proteins in solutions. They enable label-free analysis and reveal individual molecular properties, which are generally masked by ensemble averaging. Having control over the pore dimensions is vital to ensure that the dimensions of the molecules being probed match that of the pore for optimization of the signal to noise. Although nanopipettes are simple and easy to fabricate, challenges exist, especially when compared to more conventional solid-state analogues. For example, a sub-20 nm pore diameter can be difficult to fabricate and the batch-to-batch reproducibility is often poor. To improve on this limitation, atomic layer deposition (ALD) is used to deposit ultrathin layers of alumina (Al2O3) on the surface of the quartz nanopipettes enabling sub-nm tuning of the pore dimensions. Here, Al2O3 with a thickness of 8, 14 and 17 nm was deposited onto pipettes with a starting pore diameter of 75 ± 5 nm whilst a second batch had 5 and 8 nm Al2O3 deposited with a starting pore diameter of 25 ± 3 nm respectively. This highly conformal process coats both the inner and outer surfaces of pipettes and resulted in the fabrication of pore diameters as low as 7.5 nm. We show that Al2O3 modified pores do not interfere with the sensing ability of the nanopipettes and can be used for high signal-to-noise DNA detection. ALD provides a quick and efficient (batch processing) for fine-tuning nanopipettes for a broad range of applications including the detection of small biomolecules or DNA-protein interactions at the single molecule level.
Ivanov AP, Actis P, Jönsson P, et al., 2015, On-demand delivery of single DNA molecules using nanopipettes, ACS Nano, Vol: 9, Pages: 3587-3595, ISSN: 1936-086X
Understanding the behavioral properties of single molecules or larger scale populations interacting with single molecules is currently a hotly pursued topic in nanotechnology. This arises from the potential such techniques have in relation to applications such as targeted drug delivery, early stage detection of disease, and drug screening. Although label and label-free single molecule detection strategies have existed for a number of years, currently lacking are efficient methods for the controllable delivery of single molecules in aqueous environments. In this article we show both experimentally and from simulations that nanopipets in conjunction with asymmetric voltage pulses can be used for label-free detection and delivery of single molecules through the tip of a nanopipet with “on-demand” timing resolution. This was demonstrated by controllable delivery of 5 kbp and 10 kbp DNA molecules from solutions with concentrations as low as 3 pM.
Pitchford WH, Kim H-J, Ivanov AP, et al., 2015, Synchronized Optical and Electronic Detection of Biomolecules Using a Low Noise Nanopore Platform, ACS NANO, Vol: 9, Pages: 1740-1748, ISSN: 1936-0851
Ivanov A, Sanchez V, 2015, Variance reduction in high resolution coupled Monte Carlo-thermal-hydraulics calculations, Pages: 1981-1994
This paper presents the methodologies implemented in the coupled code system between MCNP and the in-house code SUBCHANFLOW to improve the variance of the fission heat deposition. Reducing the variance is essential for the uniform convergence of the large-scale criticality calculations with thermal-hydraulic feedback. The power distribution and the criticality eigenvalue depend on local material temperatures throughout the reactor core. To ensure simulation accuracy, this temperature dependence should be included in nuclear calculations for reactor analysis and design. In essence the coupled Monte Carlo - thermal-hydraulics calculations involve a series eigenvalue calculations that take into account the distributions of the density and the temperature within the nuclear reactor core. Therefore, these type of calculations have all the problems of the usual eigenvalue calculations when applied to high dominance ratio problems, among others, slow convergence of the power iteration method and large tally variances. Since the fission heat deposition is used as boundary conditions it has to be estimated within acceptable statistical accuracy. Otherwise the large variances that propagate to the temperature distributions lead to convergence failure and extensive run times. To resolve this issue and make the simulation of real reactor core geometries, adequate variance reduction techniques have to be implemented in the Monte Carlo codes.
Sanchez V, Ivanov A, Hoogenboom JE, 2015, Towards the development of coupled Monte Carlo/subchannel thermal hydraulic codes for high-fidelity simulation of LWR full cores, Pages: 1968-1980
Recent investigations are focused on the development of coupled Monte Carlo / thermal hydraulic solvers to provide high-fidelity simulations of pin clusters, fuel assemblies, fuel assembly clusters and full cores taking into account local thermal hydraulic feedback effects in the Monte Carlo neutron transport simulations. At KIT, the developmental work is focused on the Monte Carlo / Thermal Hydraulic (MC-TH) coupled solutions for industry-like applications meaning high-accuracy prediction of local parameters using fast running and validated solutions. To achieve these goals, break-through innovative methods must be implemented in order to simulate full cores with high accuracy in acceptable computing time. For this purpose, KIT is developing novel coupling approaches between MCNP and SUBCHANFLOW. Those include internal coupling of codes, on-the-fly thermal hydraulic feedback treatment during the calculation of the neutron transport, introduction of the collision estimator to tally fission heat deposition and special treatment of the temperature dependence of the thermal scattering data. Since the estimation of a fixed point is of interest, the stochastic approximation was implemented to accelerate the convergence of the coupled calculation. The stochastic approximation technique significantly accelerates the standard fixed point iteration and ensures uniform convergence. This paper presents selected results obtained with the coupled MC/TH codes for large scale geometries at pin-level.
Hoogenboom JE, Ivanov A, Sanchez V, 2015, Maximum efficiency in massively parallel execution of Monte Carlo criticality calculations, Pages: 1436-1448
The parallel efficiency of Monte Carlo codes in reactor criticality calculations is deteriorating at large numbers of processor cores. Many useful improvements to the structure of Monte Carlo codes are discussed to improve the parallel efficiency. Major improvements are running almost independent tasks on different computer nodes and limiting the execution time of the simulations per node to a maximum wall clock time. In a demonstration calculation with an improved version of MCNP5 for a full-size reactor core it was shown that the parallel efficiency when using 2,048 computer nodes each with 16 processor cores was 99 % of the theoretical maximum.
Crick CR, Albella P, Ng B, et al., 2014, Precise Attolitre Temperature Control of Nanopore Sensors using a Nanoplasmonic Bullseye, Nano Letters, Vol: 15, Pages: 553-559, ISSN: 1530-6992
Targeted temperature control in nanopores isgreatly important in further understanding biological molecules.Such control would extend the range of examinablemolecules and facilitate advanced analysis, including thecharacterization of temperature-dependent molecule conformations.The work presented within details well-definedplasmonic gold bullseye and silicon nitride nanoporemembranes. The bullseye nanoantennae are designed andoptimized using simulations and theoretical calculations forinteraction with 632.8 nm laser light. Laser heating wasmonitored experimentally through nanopore conductancemeasurements. The precise heating of nanopores is demonstratedwhile minimizing the accumulation of heat in the surrounding membrane material
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