Assuring Food Quality and Safety;
Development of Analytical Tools bases on LC-MS Technologies

Natacha Lourette, DSMResolve

Over the last decade, food quality and safety have received increased attention by authorities and industry. Here, the determination of the composition (quality) and the presence of possible toxins or pollutants (safety) play a profound role. With its widespread applicability, liquid chromatography coupled to mass spectrometric detection opened new window in food analysis and safety assessments.

In this communication, the experiences and competences at DSMResolve in these fields are highlighted. Amongst others, special attention will be given to, the characterization of food packaging (leaching of compounds) materials, lipid profiling and content determination in food and the classification of eggs by the assessment of so-called “molecular fingerprinting” by LC_MS, translating the analytical data applying chemometric tools.

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Ionic-Liquid Based Electrochemical Ethylene Sensor
Marcel Zevenbergen, Imec/Holst centre

We introduce an electrochemical sensor that exploits a thin ionic-liquid (IL) layer as electrolyte to detect ethylene, a plant hormone that induces ripening in fruit. We show that the sensor exhibits a linear response up to 10 ppm with a detection limit of 1 ppm, which is a useful range in fruit quality monitoring.

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Porous electrode millifluidics: separation of divalent from monovalent cations using capacitive deionization
Maarten Biesheuvel, Wetsus

Capacitive Deionization is an energy-efficient millifluidic flow technology for water desalination where ions are removed from water by the action of an electrical field between two porous electrodes. We discuss various novel results, such as the separation of divalent cations from a mixture of ions of different valencies. An upconcentration of 70 for Ca²⁺ has been achieved in a two-stage process.

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Enzyme-Catalyzed Modification of Surface Properties
Norhan Nady, Wageningen University & Research Centre

Influencing surface properties has already become a key technology in various industrial applications. Surfaces are modified either to minimize undesired
interactions that reduce the performance (e.g. adsorption or adhesion, leading to fouling), or to introduce additional interactions (binding or catalytic
properties) for improving selectivity or creating an entirely novel (separation) function. Grafting has emerged as a simple, stable, and versatile approach to
incorporate functional groups, such as amine, amide, or carboxylic groups that result in altered physical or chemical surface properties. However, the used grafting methods usually require harsh reaction conditions, and that is undesirable from an environmental point of view. We proved that it is possible to covalently link phenolic compounds such as 4-hydroxybenzoic acid and gallic acid to poly(ethersulfone) (PES) surfaces using laccase, an enzyme from Trametes versicolor that can catalyze the grafting reaction in aqueous medium at atmospheric conditions [1]. Spectroscopic investigations indicated that the phenolic acids were mostly covalently linked to the PES surface via their oxygen atoms. Surface modification led to improved performance, as shown by decreased adsorption of proteins, polysaccharides and polyphenols. The enzyme-catalyzed modification method shows remarkable flexibility and also allows careful tuning of e.g. the properties of PES membrane in such a way that the binding of all three tested foulants can be suppressed. Studies on the inhibition of cell adhesion and biofilm growth are currently underway.

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Functionalized Vertical InAs Nanowire Arrays for Gas Sensing
Peter Offermans, Holst Centre

Gas sensing with vertically integrated functionalized InAs nanowire arrays is demonstrated. InAs nanowires are contacted ohmically in their as-grown locations using an air bridge construction which allows gas adsorption and surface modification with molecules that are gas specific. Functionalization with Hemin enables the selective detection of NO and NO2 concentrations at the ppb-level.

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Electrical Characterization of Multilayered DNA Architectures
Louis de Smet, Delft University of Technology

Electrochemical Impedance Spectroscopy (EIS) has been used to study in great detail the adsorption of alternating layers of polycations and polyanions (including DNA) to form stable polyelectrolyte multilayers (PEMs) on a thin oxide layer of doped silicon semiconductors. The addition of each layer affects the system capacitance, which can be readily understood in terms of changes in the space charge region.

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Integrated Thermal and Microcoriolis Flow Sensing with a Dynamic Flow Range of More than 4 Decades
Joost Lötters, Bronkhorst High-Tech

We have realized a micromachined single chip flow sensing system with an unprecedented ultra-wide dynamic flow range of more than 4 decades, from less than 0.1 up to more than 1000 μl/h. The system comprises both a thermal and a micro Coriolis flow sensor with partially overlapping flow ranges.
Operation principle The thermal flow sensor, as shown in figure 1a, consists of a silicon nitride microchannel that is freely-suspended over an etched cavity in the silicon substrate. Two resistors, that fulfill both the heating and sensing function, are positioned on each channel segment. The resistors are connected in a Wheatstone bridge configuration. A flow through the channel results in a corresponding output voltage of the Wheatstone bridge. A Coriolis type flow sensor consists of a vibrating tube. Fluid flow inside the vibrating tube results in Coriolis forces that can be detected. The tube is actuated using Lorentz forces in a torsional mode indicated by ωam. A mass flow Φm inside the tube results in a Coriolis force Fc. The Coriolis force is capacitively detected by its induced out of plane vibration mode with an
amplitude proportional to the mass flow.

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X-rays Exploring the Nano Domain: a Unique Combination of SAXS and XRD
Peter Munk, PANalytical

This presentation reports on the development of a unique combination of X-ray diffractometer (XRD) with an integrated vacuum Small Angle X-ray Scattering (SAXS) module, as well as further development of application methods to characterize geometrical and behavioral properties of nanoparticles,
nanocomposites and nanostructures, such as particle sizes and size distribution, pore size and active surface area in a variety of dispersion media, in
particular nanoparticles in the range 1-100 nm, both single and composite phased. The project combines a wide variety of XRD techniques and SAXS on one laboratory instrument, allowing to characterize properties of relevant specimens, which would otherwise only be possible at synchrotron beamlines. Nanosized materials applicable for characterization are covering a very wide range, from well-defined inorganic particles/composite particles, like catalysts and highly porous carrier materials, to proteins/biomaterials including polymer-based potential drug carriers. Several interesting analysis results will be shown and discussed. This project runs under the current NanoNextNL program 2011

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Application of XPS to Surfaces and Nano-scale Materials Characterisation
Cees Heijboer, Thermo Fisher Scientific

X-ray photoelectron spectroscopy (XPS) is an analytical technique which is used to characterise surfaces, thin films and ultra-thin films. It provides quantitative elemental and chemical state information. The XPS signal is derived from the near surface region, typically from within 10 nm of the surface, making the method ideal for the characterisation of modern ultra-thin films (e.g. self-assembled monolayers, high-k dielectric materials used in modern transistors etc.). For thin films the technique is combined with sputtering so that layer structures up to a few micrometers in thickness can be characterised. The technique can be used in imaging mode to produce elemental maps, chemical state maps, layer thickness maps etc.

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EUV Resist Metrology with the Scanning Helium Ion Microscope (HIM) – Benefits and Limitations
Jeroen Meessem, ASML

HIM is a new and promising imaging technique for the inspection and metrology of surfaces with Critical Dimensions (CDs) in the 1-100 nm range. This paper presents pros and cons of HIM and existing techniques like SEM, AFM and optical CD inspection. We will also present experimental results obtained with a scanning HIM and provide a limited benchmark of those results against state-of-the-art CD-SEM.

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Monte Carlo Simulations for Contrast and Detection in SEM
Eric Bosch, FEI Electron Optics

The resolution of modern scanning electron microscopes (SEMs) is now well below 1 nm, even for probe energies below 1 keV. The next challenge in SEM imaging is obtaining a maximum amount of information from given samples. Optimization of contrast and detection is therefore an important aspect of the design of modern SEMs. This requires knowledge of which electrons carry the contrast and strategies to get these on a detector.
To this end, a Monte Carlo tool for the simulation of the interaction of electrons with matter was developed. The tool is based on the Geant4 platform developed at CERN but with extensions that allow the accurate prediction of low energy (<50eV) interactions, required for the simulation of SE generation.
In order to facilitate detector design and optimization, a detailed model of the electromagnetic fields from actual SEM columns can be included in the model. This addition allows ray tracing of secondary and backscattered electrons through the column, while the Monte Carlo model handles the interactions of electrons both with the sample and with the different parts of the SEM column. The resulting simulation model is used to study and optimize contrast formation in SEM imaging as well as optimizing the detector performance. Simulation results are compared to experimental results including a wide range of experimental conditions. Simulated contrast to noise ratios (CNR) are generally accurate to within 10% of the measured values.

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Nanoprobing InAs Quantum Dots and Wetting Layers with Atom Probe Tomography and Cross-Sectional Scanning Tunneling Microscopy
Joris Keizer, Eindhoven University of Technology

Material analysis at the atomic level is one of the key driving forces behind current progress in nanotechnology. Only recently atom probe tomography (APT) became practicable for the atomic scale characterization of semiconductor materials in 3D. We have characterized epitaxially grown InAs/GaAs quantum dot (QD) layers with both the emerging technique of APT and the well established technique of cross-sectional STM. The composition of the wetting layer and the QDs was studied. The two techniques were linked by finite element calculations that model the outward relaxation of the cleaved surface. The analysis afforded by the combination of these two techniques provides levels of insight that were hitherto unobtainable, highlighting previously neglected features in QD structures. Cross-sectional view of a typical QD imaged by APT Comparative view of two QDs imaged by STM and APT

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X-Ray Methodology for Monitoring of Protein Aggregation in Solution
Vladimir Kogan, DANNALAB

Many neurodegenerative diseases are characterized by the formation of self-assembled protein nanostructures leading to loss of functional physiological
interactions. In Parkinson’s disease, the toxicity of protein aggregation has been assigned to oligomeric aggregation intermediates. Little is however known about the structure of oligomeric intermediate(s) and their role in the aggregation pathway. Here we report on the development of a dedicated methodology that makes possible the in-situ x-ray monitoring and structural nanoscale characterization of protein aggregation. . We report on the interfacing of the device for reagent addition, sample mixing and temperature control with a standalone small angle Xray scattering (SAXS) instrument. This approach allows us to monitor the structure of equilibrium aggregation intermediates and to follow fibril nucleation and elongation as a function of time. Ultimately this setup will make it possible to screen for drugs that inhibit the formation of aggregation intermediates.

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Frequency-Selective Rotation of Magnetic Nanoactuators for Rapid and Sensitive Solution-Based Detection of Biomolecules
Menno Prins, Philips Research /  Eindhoven University of Technology

We describe an optomagnetic bionanotechnology in which nanoactuators made from bio-active magnetic nanoparticles undergo frequency-controlled rotational motion. The scattered light relates to the number, the size and the magnetic properties of the nanoparticle clusters. We demonstrate rapid and sensitive cluster assays with sub-picomolar detection limit in buffer and in human plasma.

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Nano-Particles - Bio Interaction Studies using Advanced Electron Microscopy Techniques
Jan Andries Post, Utrecht University

It is important to investigate the biological effects of nanoparticles (NPs). Do NPs interact with cells, do they enter the cells, where do they accumulate and is cellular function affected? A combination of cell biology, cellular electron microscopy and analytical electron microscopy is used to investigate the (3D) distribution of nanoparticles within a biological relevant setting.

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From Solution to Surface Gradients
Sven Krabbenborg,  MESA+ Institute for Nanotechnology, University of Twente

In this work an interdigitated electrode array is used to form gradients in solution. A pH or Cu(I) gradient was electrochemically formed. The dynamic nature of the gradients was shown and the solution gradient was transferred to the surface via the pH dependent imine-bond formation/hydrolysis or the Cu(I)-catalyzed azide-alkyne cycloaddition (click reaction).

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Organic Surface Modification: a Key Process for Micro and Nanotechnology Based Devices
Luc Scheres. Surfix

In the emerging field of micro- and nanotechnology the relative surface area exposed increases rapidly as device structures become smaller and smaller. As a result surface properties start to play a considerable role, or might even overwhelm the properties of the underlying bulk material, by this means seriously affecting lifetime, quality, and performance of the device. There is no doubt that in order to develop new functional micro- and nano-scale devices unprecedented understanding of and control over the surface properties is essential. By using the toolbox of organic chemistry, functional organic surfaces comprising catalysts, sugars, antibodies, etc., can be prepared with relative ease. In addition, because the organic surface modification is a UV light induced process, which enables photolithography, the potential of this technology is compatible with micro- and nanotechnology and can be exploited to the fullest. As test cases for application in micro- and nanotechnology, organic surface modification of microcapillary electrophoresis (mCE) chips, AFM tips, and microengineered culture chips is being explored. Our latest result on these three topics will be discussed in detail.

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Scale-up of Multiphase Micro/Milli Channel Reactors
Ma'moun Al-Rawashdeh, Eindhoven University of Technology

Microstructured reactors are already at the production scale for single phase processes, for example, in fine-chemical applications in liquid phase and in fuelprocessing in gas-phase. However, gas-liquid micro processing remains mostly restricted to laboratory scale due to the complexity and expenditure needed for an adequate numbering-up with an equal distribution of the gas and liquid flows over multiple microchannels. Previously, we developed a barrier-based gas-liquid flow distributor. It was used for a water-nitrogen flow under the Taylor flow regime. Gasliquid channeling was prevented and a flow uniformity of more than 90% was achieved. Based on this “barrier channels” concept, a design strategy was developed for reaching sufficient flow uniformity. This strategy was used for designing the ‘Barrier-based Micro/Milli Reactor’ (BMMR).  The BMMR is a modular reactor for conducting a multiphase (gas-liquid) reaction in parallel micro or milli channels at a pressure up to 20 bar and a temperature up to 200 oC with a liquid flow rate of 150 mL/min. According to this design strategy, the appropriate fabrication techniques were chosen to deliver a flow uniformity of more than 90% in the BMMR. In the barrier channels, the fabrication tolerance (σ) of less than 2% was realized via wet chemical etching in glass. Powder blasting in glass was used in the mixer channels to achieve σ less than 5%. Milling in stainless steel was used in the reaction channels to reach σ below 10%. To verify the developed design strategy, the flow uniformity at different operating conditions has been investigated in the BMMR under cold flow conditions (without reaction). The influence of channel blockage on the reactor performance has also been studied.

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A Microfluidic Method to Assess Emulsion Stability in Crude-Oil/Water Separators
Thomas Krebs, Wageningen University & Research Centre

The control of emulsion stability and droplet size is of crucial importance for oil production, especially for the processes of crude/oil water separation and cleanup of produced water. To recover pure oil and water, coalescence between droplets needs to take place, the extent of which will depend on the flow parameters as well as on the presence of emulsifying agents. For a successful separation, the demulsification time of the mixture must be smaller than its residence time in the separator. A direct measurement of the coalescence rate in dense flowing emulsions has not been achieved until now. In this work we present a microfluidic method that permits to assess the kinetic parameters governing coalescence in flowing emulsions.
Monodisperse droplets of oil in water formed at a microfluidic T-junction were injected into a wide channel where droplets are accumulated to form a twodimensional emulsion layer (see figure). The droplets undergo collisions and coalesce. The coalescence process was followed with a microscope and a highspeed camera. Counting the number of coalescence events permits to calculate the coalescence rate and evolution of the droplet size distribution, which were mapped as a function of initial droplet size, flow rate and dispersed phase volume fraction.
The results obtained provide information about the timescale of separation of the liquid mixture and may thus help in the design of the separation process for a given produced fluid.

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Meander Reactor with G/L Contacting and Electrokinetic Separation Functionalities
Elif Karatay, University of Twente

There is a substantial growth in the integration of unit operations on microfluidic devices. By means of integrating repetitive mixing, conversion and separation functionalities in a microreactor, high reaction selectivity at high conversion can be possible for reactions that traditionally do not give reasonable yields. The proposed system of study is the production of hydroxylamine from ammonia via partial oxidation. This reaction is known to occur at very low conversions. To achieve high reaction selectivity and high conversion, a multiplexed reactor is developed in which the reactant dissolved oxygen is dosed in a controlled manner and reaction product, hydroxylamine, is removed selectively. Meander microchannels are saturated with oxygen by two different methods. Porous, hydrophobic, home-made PVDF membranes are used to feed oxygen to the reactor. G/L contacting is also studied with a silicon-glass micro device including tiny side channels between gas and liquid micro channels enabling the formation of bubble mattresses and saturation of liquid channel with oxygen by controlling gas side pressure. Hydroxylamine is removed from the reaction medium, which is mainly composed of ammonia, based on charge differences; by means of applying an electric field across a nanojunction including an ion selective Nafion membrane and pressure driven flow, it is proposed to divide the reaction mixture at a specific pH into two streams, one with a high ionic conductivity mainly composing of ammonium, and the other one including neutral hydroxylamine. During operation, it is possible to isolate ion enriched and ion depleted zones and hence to push away the charged species from the Nafion nanojunction [1]. In order to investigate the separation and mass transfer mechanisms, this non-linear non-equilibrium process is also analyzed numerically. The full model including the Nafion nanoslot membrane is based on classical Poisson, Nernst-Planck, Navier-Stokes equations.

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Advanced Processes in Microreactors
Bas van den Broek, FutureChemistry

Objectives: Continuous processing in microreactors is increasingly used for the past decade and shows high potential in chemical synthesis allowing simple (catalytic) procedures and shows enhanced safety over batchwise production. In addition, a fast optimisation with regard to the amount of substrate, reaction time and temperature can be performed. This drastically accelerates the search for the optimal parameters of a process. Here we present the opportunities and diversity FutureChemistry’s microreactortechnology1 offers in thermically and chemically hazardous processes difficult to perform batchwise and at large scale. Results: The exothermic Vilsmeier-Haack formylation has been investigated in which the in situ formed iminium ion (Vilsmeier-Haack reagent) reacts to the corresponding aldehyde. Previous (calorimetric) studies have demonstrated that this reaction poses specific thermal hazards as the Vilsmeier-Haack reagent is thermally unstable and can generate high and fast temperature rises when heated resulting in a thermal runaway2. In a microreactor, the reaction takes place on a microliter scale which allows excellent heat dissipation and makes active cooling of the system unnecessary. In the microreactor setup, a quantitative conversion (>99%) was obtained with a throughput of 6.0 g/h after optimisation. This approach enables the Vilsmeier-Haack formylation at industrial scale. In addition to the Vilsmeier-Haack formylation, the chlorination of primary and secondary alcohols, with formation of the chlorophosphonium salt, and peptide synthesis, with activation of the amino acid, have been investigated, analogue to the Vilsmeier-Haack formylation. Conclusions: A diversity of chemical processes has been developed, demonstrating the potential of FutureChemistry’s B200 Flowstart system. The results show the enhanced safety and ease of use for intrinsic hazardous processes.

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A Flexible Flow Platform for Rapid Reaction Screening and Process Scale-up under High Temperature and Pressure Conditions
Theo Veenstra, LioniX

Throughout the numerous stages of chemical process development there are many associated risks; perhaps none as costly as the failure to scale-up a
synthetic process to achieve the desired production capacity of a key intermediate or API (Active pharmaceutical ingredient). Whilst the emerging technique of micro reaction technology enables those working in R&D to rapidly screen ‘extreme’ reaction conditions using continu ous flow, the production volume of such units is inherently small. It has long been discussed that once identified, the optimal reaction conditions can be used to increase production volume using a combination of continuous operation and/or numbering-up. Looking at this from a commercial stand-point however, it becomes clear that this is not economically feasible as to produce chemicals on a tonnes annum-1 scale would require hundreds to thousands of micro reactors; consequently, at a certain point it is necessary to increase the reactor volume. With efficient heat and mass transfer being key to the success of micro reactors, it is imperative that these features are retained when the reactor volume is increased. Otherwise the same ‘failure to scale’ scenario would be encountered; resulting in the need for costly re-optimisation steps. With this in mind, we present new data which validates our up-scaling principle of taking optimal conditions from Labtrix® micro reactors (1-20 μl) to Plantrix® meso reactors (0.8 to 6.5 ml) without a loss of mixing performance and demonstrate the suitability of such reactors for the performance of synthetic transformations, such as SNAr reactions, under high temperatures (195 ºC) and pressures (25 bar). Illustration of the glass meso reactor (0.8-6.5ml) 4th Bourne reaction used for mixing quantification

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Measurement of Platelet Activation with Anti-P-selectin Coated Magnetic Microparticles
Loes van Zijp, Eindhoven University of Technology

Under normal conditions, platelets have very little interaction with each other or with other cells. However platelets become activated for instance, when they are exposed to collagen by vascular damage. Upon activation, several molecules get exposed on the cell membrane to support adhesion, spreading and aggregation of the platelets onto the damaged vessel. Platelet activation is involved in cardiovascular diseases. Traditionally, platelet activation is quantified with fluorescent markers in combination with flow cytometry. However flow cytometry requires complex and expensive equipment.
We are studying novel technologies for platelet activation biosensors that are inexpensive and require minimal sample preparation. We present a proof of principle measurement of platelet activation with magnetic particles. Particles coated with anti-P-selectin were used to remove activated platelets from samples stimulated with different concentrations of activation agonists. We analyzed the platelet activation level by measuring the remaining unbound cells in the solution. We compared our new approach to traditional flow cytometry and found good agreement (figure). Our cell removal assay has the potential to be used in integrated cell biosensors which don’t rely on fluorescent labeling and detection of cells.

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Biosensor with Single-Label Resolution Based on Optical Scattering of Magnetic Nanoparticles
Jean Schleipen, Philips Research

Biomedical research delivers detailed knowledge about how specific molecules relate to human health and disease. Such specific molecules are called
biomarkers when they can be used for diagnostic purposes. For example, the presence of certain protein biomarkers in blood indicates the onset of a heart attack. To enable wide-spread application of biomarker testing, biosensor systems are needed which can easily be used by doctors and patients. The requirements are challenging: the systems need to be highly sensitive, reliable, cost-effective, rapid, and very easy to use. Smart integrations of bio-technologies with micronano-technologies are being investigated in order to meet the application demands. In this paper we present a novel sensing technology for very high sensitivity biosensor assays with single-label and single-molecule resolution. The system is based on microscopy-based dark-field detection of scattering of bio-active magnetic nanoparticles. As a result, the detection of nanoparticles and biomolecules is a digital process (see Figure 1) and the system sensitivity will ultimately be governed by counting statistics. In this talk we will present an overview of the biosensor instrumentation and we will show our latest assay results.

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Capture of Unamplified Mycobacterial rRNA on a Liquid Bead Array for Species Determination from Liquid Cultures
Richard Anthony, KIT - Royal Tropical Institute

Here we present a multiplex method with the potential to be simpler than an DNA amplification / DNA array approach, for bacterial species identification. To achieve this a crude extract bacterial NA is hybridized to a "liquid bead array" composed of fluorescently encoded magnetic beads coupled to specific oligonucleotides.

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Integration of Risk Analysis and Technology Assessment in Nanotechnology Development
Arie Rip, University of Twente

Theme 1 of the NanoNextNL R&D Program has to integrate risk analysis with broader considerations about governance and responsibilities. It must also link up with the other themes in the Program, and can do so with the help of sociotechnical scenarios. Promise and concern assessment is important to inform strategic decision making.

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Characterization of Translocation of Silver Nanoparticles and Effects on Whole-Genome Gene Expression Using an In Vitro Intestinal Epithelium Coculture Model
Hans Bouwmeester, Wageningen University & Research Centre

Applications of nanoparticles in the food sector are eminent. Silver nanoparticles are among the most frequently used, making consumer exposure to silver nanoparticles inevitable. Information about uptake through the intestines and possible toxic effects of silver nanoparticles is therefore very important but still lacking. In the present study, we used an in vitro model for the human intestinal epithelium consisting of Caco-2 and M-cells to study the passage of silver nanoparticles and their ionic equivalents and to assess their effects on wholegenome mRNA expression. This in vitro intestine model was exposed to four sizes of silver nanoparticles for 4 h. Exposure to silver ions was included as a control since 6 to 17% of the silver nanoparticles were found to be dissociated into silver ions. The amount of silver ions that passed the Caco-2 cell barrier was equal for the silver ion and nanoparticle exposures. The nanoparticles induced clear changes in gene expression in a range of stress responses including oxidative stress, endoplasmatic stress response, and apoptosis. The gene expression response to silver nanoparticles, however, was very similar to that of AgNO3. Therefore, the observed effects of the silver nanoparticles are likely exerted by the silver ions that are released from the nanoparticles.

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Biodistribution and Toxicity of Silver Nanoparticles in Rats after Subchronic Oral Administration
Meike van der Zande, RIKILT - Institute of Food Safety - Wageningen University & Research centre

In this 28-day exposure study in rats we examined the bioavailability and toxicity of silver nanoparticles (AgNPs) compared to AgNO3. Wash-out groups were also examined on days 36 and 90. Results confirm bioavailability of silver and AgNPs to organs tested. An equal silver distribution behavior between AgNPs and Ag+ suggests comparable systemic toxicity and wash-out groups showed retention of silver in testis, brain and kidney, implying an elevated toxic potential in these tissues.

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Nanoparticles in consumer products: Methods and Measurements
Ruud Peters, RIKILT - Institute of Food Safety - Wageningen University & Research centre

Products based on nanotechnology or containing engineered nanoparticles are beginning to impact consumer products and food. As a consequence direct and indirect consumer exposure to nanoparticles is likely. We have developed and applied a number of methods for the detection and characterization of nanoparticles in food, consumer products and in biological samples. Methods will be briefly introduced and results of the analysis of food, consumer products and biological samples will be discussed.

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Cationic Thermosensitive Liposomes - a Novel Heat-Triggered Drug Delivery Approach for Endothelial and Tumor Cells
Bilyana Dicheva, TLM, Laboratory Experimental Surgical Oncology

Introduction. Cationic liposomes have strong affinity for angiogenic endothelial cells and tumor cells. We aim to develop PEGylated cationic thermosensitive liposomes (CTSL) to increase the therapeutic efficacy of chemotherapy by enhanced particle retention in tumors followed by heat-triggered drug release. Methods. CTSL and noncationic TSL were prepared with entrapped carboxyfluorescein (CF) representing encapsulated drugs. Temperature and timedependent release profiles of CF were established by fluorometry. CTSL and TSL binding to melanoma (BLM) and endothelial cells (HUVEC) was studied by flow cytometry. Intra-and extracellular content release was studied by confocal microscopy. Intravital microscopy on tumors implanted in dorsal skin-fold window chamber-bearing mice was performed to study CTSL binding to endothelial and tumor cells and content release upon heat. Results. CTSL released the entrapped CF rapidly at 43 ıC. CTSL bound in vitro to a higher extent to BLM and HUVEC than TSL. Hyperthermia (HT) of 43 ıC induced intra - and extracellular CF release in BLM and HUVEC cells. Intravital microscopy experiments in B16BL6 and LLC tumors displayed binding of CTSL to tumor vasculature and tumor cells and massive intratumoral CF release upon HT. Summary. The developed cationic thermosensitive liposomes have a higher ability to bind to tumor cells and endothelial cells than TSL and demonstrate heat triggered release both in vitro and in vivo. Therefore, CTSL represent a promising new trigger-induced delivery system for improved drug delivery to solid tumors.

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The Application of Micro-and Nanofluidics in Wobbe Index Meters
Albert Mouris, Hobré Instruments

A new concept for Wobbe Index, Heating Value and Air Demand analysis of gaseous fuels is introduced. This technology enables the analysis of fuel gas properties at a fraction of the current costs. Applications include monitoring of gas grid entry specifications (for example biogas) and optimization of small gas fired combustion processes.

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Thermal Transpiration Studied as a Time-Dependent and Non Time-Dependend Phenomenon.
Marcos Rojas Cardenas, AOES

Thermal transpiration is the macroscopic movement of rarefied gas induced by a temperature gradient. The gas moves from the lower temperature to the
higher temperature region. In recent times the advent of micro-electro mechanical systems (MEMS) made way for new perspectives on thermal transpiration. The possibility of using the pumping effect of thermal transpiration to create a micro-compressor is one of them. Here an original method is proposed to measure the mass flow rate induced by the phenomenon along a circular cross-section micro-tube where a temperature gradient is induced along its surface. This is done in order to characterize what could be a precise system of gas flow control. The experimental methodology is based on the constant volume measuring method where the dynamic pressure-response in time of the system is monitored and analyzed. The experimental setup is composed by a glass micro-tube connected to two external reservoirs where the pressure is monitored by means of two capacitance diaphragm gauges. An infrared camera monitors the temperature gradient along the glass tube's surface and the test section is hold constantly under vacuum conditions. The experiments are conducted for three different gases and for different temperature differences which are imposed between inlet and outlet of the tube. For these experimental conditions and for the here used tube the gas rarefaction goes from transitional to slip regime. Second aim of this work is to investigate, by using the direct simulation Monte Carlo method, the intensity of parasite thermal transpiration effects which are intrinsically present in commonly used capacitance diaphragm internally-heated gauges. This parasite effects affect the absolute measured pressure value given an error which is function of the gas rarefaction, the gas nature, the gas temperature and the gauge source temperature.

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The Phaseguide Paradigm: Priming and Emptying of Monolithic Polymer Chips
Sebastiaan Trietsch, Leiden University

Conventional chip design is limited by the need for proper priming and emptying. Phaseguide technology gives complete control over filling and emptying of any shape of microfluidic structure by utilizing passive capillary pressure barriers, typically in the form of ridges in the channels or chambers. Phaseguides control fluid flow for complete filling and emptying of glass-hybrid or monolithic polymer chips.

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Directional Wetting on Chemically Patterned Substrated
Stefan Kooij, MESA+ Institute for Nanotechnology, University of Twente

The ability to control liquid behaviour at surfaces is highly relevant for a number of application areas, including for example the performance and reliability of inkjet nozzles. Generally, the wettability of solid substrates can be modified both by morphological micro-and nanostructuring as well as by chemical functionalization. Here we explore the potential of chemically defined patterns consisting of hydrophobic self-assembled monolayers (fluoroalkylsilane) on hydrophilic (pristine SiO2) substrates to control dynamic liquid behaviour on morphologically flat surfaces. We review our recent results on the wetting behaviour of chemically stripe-patterned anisotropic surfaces [1,2]. The equilibrium shapes of asymmetric droplets, arising from patterns of alternating hydrophilic and hydrophobic stripes with dimensions in the low-micrometer range, are investigated in relation to the stripe widths. Owing to the well-defined small droplet volume, the equilibrium shape as well as the observed contact angles exhibit unique scaling behaviour as a function of the relative hydrophobicity. Additionally, high-speed camera measurements reveal the kinetics involved in the formation of the asymmetric droplets. We also present results of experiments investigating the motion of the liquid from surface areas with low macroscopic wettability towards areas with a higher wettability. The density of self-assembled fluoroalkylsilane monolayers as defined by the chemical patterning proves to be of paramount importance. Both linear
and radial patterns are presented, which induce liquid movement across chemically defined gradients in surface energy.

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Thermal-Hydraulic Performance of a Counter-Flow Heat Exchanger in a Micromachined Cryocooler
Haishan Cao, University of Twente

Micromachined cryogenic coolers were developed at the University of Twente that work on basis of the Joule-Thomson (JT) effect. A single-stage JT microcooler with a cooling capacity of about 10 mW at 100 K has been realized. In this present study, research aimed at developing a two-stage 30 K JT microcooler is presented. 

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New materials for luminescent and non-luminescent solar concentrators
Dick de Boer, Philips Research

Concentrator systems help to minimize the amount of solar-cell area for photovolataics. Luminescent concentrators would allow for high concentration if losses by reabsorption and escape could be minimized. We present new phosphors and filters for this. Another type of concentrators is diffraction based. We discuss first results and plans for concentrators in which luminescence and diffraction are combined.

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New method to Characterize Light Trapping in Ultra-Thin Thin Solar Cells
Jorik van de Groep, FOM Institute for Atomic and Molecular Physics

Thin-film solar cells are advantageous compared to their thick counterparts, as they can be made at lower costs, show larger open circuit voltage, enhanced current collection and (in some cases) lower photodegradation. However, thin cells exhibit poor light absorption. Light trapping schemes such as random texturing of the front surface are commercially applied to enhance absorption inside the active layer. However, for ultra-thin solar cells such large-scale texturing is difficult to realize, and leads to unwanted surface recombination. Recently, plasmonic nanoparticles printed on top of the solar cell have proven to be an efficient light trapping scheme as they allow light to couple to the waveguide modes supported by thin films.
In this work a Silicon-On-Insulator wafer with a 200 nm Si waveguide is used as a model system for solar cells to investigate the mechanism of light coupling to waveguide modes in ultra-thin optically active layers. Two-dimensional arrays of silver nanoparticles with a diameter varying between 270-300 nm and pitch between 500-700 nm were made on top of the SOI wafer using Substrate Conformal Imprint Lithography. Spectrally resolved total reflection measurements showed clear reflection dips that correspond to light coupling to waveguide modes, in agreement with calculations and simulations. To prove that light is absorbed inside the waveguide, erbium ions were implanted inside the waveguide. The Photoluminescence (PL) of the erbium ions was used to directly probe the intensity enhancement. Angular resolved measurements by varying the incident pump beam (wavelength 980 nm), show clear peaks in the PL intensity enhancement as a function of angle, that are assigned to coupling to well-defined waveguide modes. Light trapping intensity enhancements up to a factor 9 are observed. This work directly demonstrates that that light absorption in a semiconductor layer is strongly enhanced due to the scattering from plasmonic nanoparticles.

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Nano-Opto-Electro-Mechanical Photonic Crystal Cavities
Andrea Fiore, Eindhoven University of Technology

We present a novel method to tune a sharp optical resonance over a broad spectral range. It is based on the electro-mechanical tuning of a semiconductor photonic crystal cavity. A spectral shift exceeding 10 nm is obtained with < 6 V applied bias. The integration of a detector within the cavity may result in a fully monolithic, micron-sized spectrometer.

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Towards a predictive device model for multilayer white OLEDs
Rein de Vries, Philips Research 

In the near future LED (light emitting diode) and OLED (organic LED) technology will replace traditional light sources [1]. We present the step-by-step development of a predictive device model for realistic OLEDs, based on the results of first principles 3D Monte Carlo modeling. Such a device model can make it possible to rationally design multilayer OLEDs for efficient white lighting.

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Nanoscale Dispersion of Catalyst by Spark Discharge
Tobias Pfeiffer, Delft University of Technology

Abstract: Solid state diffusion presents the major bottleneck in hydrogen ab/desorption in magnesium-based hydrogen storage materials. This makes the distribution of catalyst within the storage material as important as the catalyst material itself. By producing catalyst particles in situ in a bulk aerosol flow, 4nm niobium particles were homogeneously dispersed down to 20nm length scales into agglomerates of ~10nm magnesium particles.

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Safe Design of Engineered NanoParticles : Synthesis of Less Toxic Luminescent Quantum Dots
Mariëlle Wouters, TNO Science & Industry

Nanomaterials display novel functional characteristics when compared to their bulk counterparts, and they offer widespread industrial possibilities. The safe use of engineered nanoparticles, such as QuantumDots (QDs) is of extreme importance in a growing market with new applications. In this contribution we will show that we are able to design luminescent engineered nanoparticles that are potentially less toxic without losing their luminescent properties.

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Optical Response of Semiconductor Quantum Dot - Metal Nanoparticle Heterodimer: Bistability and Spectra
Bintoro Nugroho, Zernike Institute for Advanced Materials

Optical bistability is an important phenomenon because of its promising applications to optical logic and signal processing. The key ingredients for bistable response to occur are an optical nonlinearity of the material and a feedback, which, if combined, may result in a multi-valued nonlinear output. We report on a theoretical study of bistable optical response of a semiconductor quantum dot (SQD) coupled to a closely positioned metallic nano-particle (MNP). The crux for the possible occurrence of bistability in this system is that the optical properties of the MNP give rise to a feedback of the SQD. As the
SQD is a nonlinear system, the hetero-dimer optical response may then exhibit bistable behavior. In our calculation, the system is assumed to be embedded in a dielectric host with the dielectric constant εb and driven by a linearly polarized monochromatic external field. The interaction between the two nanoparticles is determined by a complex coupling parameter G. It turns out that both the real and imaginary parts of G (Gr and Gi ) play a role in the occurrence of bistable optical response. From our calculations we found that at Gr = 0, the critical value for bistability to occur is Gi = 8Γ (Fig 1), while at Gi = 0, the critical value of Gr = 4Γ. Additionally, the optical bistable response results in a discontinuity of the SQD-MNP absorption spectrum, depending on which branch of the SQD population difference Z versus the incident intensity I the systems finds itself . For larger clusters of nanoparticles, such as two
interacting arrays of SQDs and MNPs, we expect that the effect can also be observed, because the MNPs still play the role of a mirror, providing a feedbackto the SQDs.

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Nanopatterning by Direct-Write Atomic Layer Deposition
Adrie Mackus, Eindhoven University of Technology

A novel approach for direct-write fabrication of Pt nanostructures based on a combination of electron beam induced deposition (EBID) with atomic layer deposition (ALD) is presented. The developed approach comprises seed layer deposition by EBID followed by area-selective ALD growth. Pt structures were fabricated with an unparalleled high material quality, which makes direct-write ALD suitable for adding electrical contacts to nanodevices.

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Diffusion Driven Self Organisation of SrRuO3 Nanowires on Ordered Surface Terminations
Gertjan Koster, MESA+ Institute for Nanotechnology, University of Twente

Complex oxides from the perovskite class provide a unique toolset of materials to the structure composition to property relationship in correlated electronic systems. By using thin film deposition techniques that allow for atomic control, one can essentially build artificial crystal structures bottom up. Hetrostructures consisting of alternating sheets of material are grown on a single terminated substrate template; typically TiO2 terminated SrTiO3, which can be obtained through well-established chemical etching procedures [1, 2]. In literature, there are examples of spontaneous self-organization of deposited material, with the starting template of the mixed variant [3]. Here we use diffusion driven self-assembly to formation of structures on ordered areas of different surface termination [4]. On (001) DyScO3 lines parallel to the vicinal steps define the regions of mixed termination. SrRuO3 appears to grow selectively on one termination. This growth type results in conducting wires of tens of nanometers wide and a few nanometers tall. One could possibly exploit this diffusion driven self organization to create not only structures of layered sheets, but in fact create more complicated heterostructures. Preliminary experiments of deposition of ferroelectric PbTiO3 demonstrate the usability of the nanowires as patterned electrodes. We have further characterized these nanowires by in situ SPM and PES, ex-situ XRD and HRTEM. We finally provide evidence for a possible growth mechanism by Monte Carlo solid-on-solid simulations.

1. G. Koster, B.L. Kropman, G. Rijnders, D.H.A. Blank and H. Rogalla, Appl. Phys. Lett. 73 (1998) 2920-2922
2. R. Bachelet, F. Sanchez, J. Santiso, C. Munuera, C. Ocal, J. Fontcuberta Chemistry of Materials 2009 21 (12), 2494-2498
3. Kleibeuker et al., Adv. Functional Mat. 2010, in press
4. Kuiper et al., submitted

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PZT Thin Film Sputter Deposition for Piezo-Electric Energy Harvesters
Madhusudhanan Jambunathan, Imec/Holst centre

Lead Zirconium Titanate (PZT) thin film based vibration energy harvesters are of great interest for frequency tuning due its actuation characteristics. Next to the actuation, the energy harvesting power output is important and is characterized by the coupling coefficient figure of merit, e₃₁²/ε_rε_o.. In this lecture, we focus on the  industry feasible reactive sputter deposited PZT film and figure of merit related factors such as deposition method, substrate choice, orientation, composition and morphology .

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Nanofluidic Devices for Single-Molecule Electrochemical Detection
Kang Shuo, MESA+ Institute for Nanotechnology, University of Twente

Developing the ability to electrically detect and manipulate single molecules in solution with high time resolution represents an ongoing challenge in fields ranging from nanofluidics, analytical chemistry and lab-on-a-chip applications. Electrochemically active molecules are particularly amenable to electrical detection since they can exchange electrons with electrodes immersed in solution. Electrochemical reactions however transfer one or few electrons per reacting molecule, rendering the direct detection of single molecules in solution virtually impossible. We have recently overcome this barrier using nanofluidic devices and so-called redox cycling, in which two electrodes are used to repeatedly flip the charge state of target molecules and thus permit each molecule to contribute a very large number of electrons to the measured current. In this talk, we introduce a new self-aligned process for fabricating redox cycling nanofluidic devices suitable for single-molecule detection. This process, which is based on optical lithography and standard microfabrication steps, is suitable for mass production. Using these devices, we further developed a method for quantifying the degree of adsorption of target analyte molecules on the electrodes. This adsorption limits the sensitivity of our devices by slowing down redox cycling. It also represents an opportunity, however, since it provides a means of controlling the magnitude of the response of the sensor to different chemical species. By controlling adsorption, we aim to develop the ability to discriminate between different molecular species in solution, providing a new form of molecular fingerprint based on electrochemistry.

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Depletion Zone Isotachophoresis: (dzITP): Beating the Simplicity of Electrophoresis
Jos Quist, Netherlands Metabolomics Centre, Leiden University

A radically new approach towards isotachophoresis is presented in which a nanochannel-induced ionic depletion zone replaces a trailing electrolyte.
Isotachophoresis (ITP) is arguably today’s most powerful electrokinetic separation and concentration technique. In practice, however, it lags in popularity to the much simpler technique of zone electrophoresis. A reason is that it needs both a leading electrolyte and a terminating electrolyte, making method development and sample introduction rather complicated. Here we present a radically different approach towards ITP employing nanofluidic phenomena. Only a single electrolyte is needed. The technique makes use of anion/cation asymmetry in a nanochannel to create a depletion zone in a H-shaped nano-microchannel setup. In the microchannel, electro-osmotic flow (EOF) opposes depletion zone growth and supplies compounds that focus at the depletion border. The focused compounds are separated into pure zones arranged in order of their electrophoretic mobility. We show the separation of four compounds in distinctive zones. Variation of voltages allows both zone sharpening and positioning. The position of the zones has little variation over time. dzITP works both for continuous and discrete sample injection. dzITP will prove particularly useful for our metabolomics research. Low abundant metabolites from complex biological samples can be separated and strongly enriched, while removing low-mobility proteins and high-mobility salts. The use of one single background electrolyte and flexible sample injection renders dzITP handling not only much simpler than conventional ITP, but also than on-chip zone electrophoresis. Furthermore, the method is quasi-static without the need of EOF suppression and 3-point voltage actuation gives full control over the analyte zones. The increased simplicity and functionality of our approach thus paves the way for claiming ITP’s rightful position as best electrokinetic separation technique, not only in theory, but also in practice.

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Integrated Microfluidic Platform for Studies on Membrane Proteins and Drug Screening Arrays
Verena Stimberg, University of Twente

The combination of microfluidics with BLM (bilayer lipid membrane) experimentation provides a promising route towards high-throughput screening platforms for studies and drug screening on membrane proteins. The microfluidic format is ideal for multiplexed and automated assays, the miniaturization of the device goes together with enhanced electrical capabilities and more stable bilayers, and dual optical and electrical measurements are possible with a horizontal configuration of the membrane. In that context, we have developed a sandwich device consisting of two glass substrates separated by a Teflon membrane. The glass substrates contain two independent and orthogonal microfluidic channels being the two fluidic reservoirs for BLM experimentation; the Teflon film presents a micrometer-size aperture, located at the intersection of the microchannels, and across which BLMs are made. Leakage-free assembly of the three layers is demonstrated using an optical adhesive. The closed configuration of the device prompted us to develop a novel methodology for BLM preparation. Lipid solution and buffer are successively flushed in both channels, so that the lipid plug deposited in the aperture spontaneously thins into a bilayer. BLM formation is monitored electrically (patch-amplifier) and optically ((fluorescence) microscopy). This lipid-plug-thinning technique gives highly stable BLMs (> 12 hrs lifetime) with an almost 100% success yield and reproducible bilayer characteristics in terms of sealing quality (G
) and capacitance (pF). Pore-forming species such as α-hemolysin and gramicidin are used to confirm the formation of a bilayer structure. Additionally, gramicidin is applied as model to study the impact of BLM properties on membrane protein activity by recording the dynamics of channel formation and their lifetime. We will present the detailed fabrication of the microfluidic platform, BLM formation and characterization in the closed environment, and on-chip single proteins studies.

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Electrocavitation in Nanochannels: A New Fundamental Effect
Kjeld Janssen, Leiden University

We present a new fundamental nanofluidic phenomenon: the liquid column in a nanochannel filled with two adjacent solutions of different conductivity
cavitates above a certain threshold voltage, visible as the sudden rapid formation of bubbles in the channel. Under a continued electric field application, the whole channel, 3.5 cm in length, would empty. Upon turning off the field, the empty section of channel was seen to refill due to capillary action. This effect is relevant for the study of the physics of fluids since it provides a controllable cavitation mechanism, and it is important for the downscaling of electrophoretic techniques in nanochannels as it puts a fundamental limit on the applicable field strength. When a nanochannel is filled with adjacent solutions of high and low conductivity, an applied potential difference will drop predominantly over the lowconductivity solution. A stronger electroosmotic flow (EOF) will therefore be induced in the low-conductivity solution and will drag the other. This imbalance puts strain on the liquid column, inducing negative pressures of several hundreds of bars. For capillarity induced negative pressure, theoretically the channels are too small to support the critical cavitation radius, rcrit [2]. However, for sufficiently high negative pressures p bubble cavitation can occur, where: rcrit=2γ/p [3]. With most of the channel at negative pressure, breakup need not occur particularly at the interface between the two electrolytes, and surface heterogeneities may also influence the position and the critical pressure required. We discovered and explained the new nanofluidic phenomenon of electrocavitation. Breakup due to gradients in EOF, puts a fundamental limit on those techniques that employ conductivity gradients for example isotachophoresis, electrochromatography and certain types of nanofluidic pumps.

1.H. Bruus, Oxford University Press, Oxford, 2007
2.N. R. Tas et al., Nano Letters 3(2003).
3.J. C. Fisher., Journal of Applied Physics 19,1062(1948).

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An On-Chip Three-Port Interferometer for Metrology and Fiber Bragg Grating Interrogation
Peter Harmsma, TNO Science and Industry

We present a three-port interferometer in Silicon-On-Insulator waveguide technology. We have already applied fiber-based three-port interferometers for Fiber Bragg Grating interrogation and displacement tracking. Our recent waveguide-based device offers improved mechanical stability, reduced size and weight, and potentially lower cost. Moreover, it can be integrated with other components on a single chip for increased functionality.

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Near-Field Study of the Scattering of Surface Plasmon Polaritons from Single Sub-Wavelength Holes
Nir Rotenberg, FOM Institute for Atomic and Molecular Physics, AMOLF

We map the complex electric fields associated with the scattering of surface Plasmon polaritons from individual subwavelength holes in gold films. We show that the scattered field is isotropic in the plane of the film, and study both its dependence on the size of the hole, as well as resolve its temporal evolution.

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Ultimate Fast Optical Switching of a Semiconductor Microcavity in the Telecom Wavelength Range
Georgios Ctistis, Mesa+ Institute for Nanotechnology, University of Twente

We present ultrafast pump-probe reflectivity measurements on GaAs-AlAs microcavities with a cavity resonance at telecom wavelengths. We have resolved the ultimate fast decrease of the cavity resonance frequency due to the instantaneous electronic Kerr effect. The dynamics of the switching process is only limited by the cavity storage time and allow for repetitive switching rates approaching the THz regime.

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Probing Radiation Patterns of Sincle Plasmonic and Metamaterial Structures

Ivana Sersic, FOM Institute for Atomic and Molecular Physics, AMOLF

Plasmonic and metamaterial nanoscatterers are excellently suited solid-state building blocks for realizing subwavelength photonic components due to their strong response to light. This response is characterized by the existence of electric and magnetic polarizabilities that when mutually cross-coupled, give rise to interesting non-isotropic radiation patterns. In this contribution, we report a new experimental technique for quantifying the distribution and directionality of light scattered by these nanoscatterers. We custom built a Fourier microscope to image radiation patterns of single photonic nanostructures. It is well known that single plasmonic and metamaterial structures have extinction cross sections that exceed their geometrical area. However, absolute cross sections scattered by single structures are still low compared to the diffraction limit, making it very difficult to detect their radiation patterns. Here we present a dark field microscopy set up for scattering experiments on single nanostructures that are essentially background free. Our sample is excited by means of total internal reflection (TIR) from a glass prism that gives rise to an evanescent wave at the surface of the prism. We use a high NA objective (NA=0.95) to collect a large range of k-vectors. In this contribution we present measurements on Au nanobars that can be viewed as simple nanoantennas composed of phased arrays of single dipoles. We show that when decreasing the nanorod length, we can detect the radiation patterns of single 200 nm Au nanorods that exhibit a single dipolar radiation pattern. This set up is a powerful tool for mapping the Fourier space of nanophotonic structures and is highly suitable for measurements on variety of plasmonic and metamaterial structures, such as gap-antennas, split ring resonators (SRRs) and cut-wire pairs. Furthermore, this new experimental set up will allow us to verify our recent theoretical predictions on the radiation patterns of SRRs at LC resonance frequencies

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Nano-Engineering with Helium Ions
Diederik Maas, TNO Science and Industry

Helium Ion Microscopy (HIM) was introduced only a few years ago, and today many new application fields are budding. On the one hand, the HIM turns out to be a viable tool for imaging of sensitive and/or charging samples at the true nanometer scale. On the other hand, the sub-nanometer sized helium ion probe enables nanofabrication through direct write, helium ion beam induced deposition and etch, as well as nanolithography at very high resolution and high pattern densities. This presentation will show some application highlights for these domains. The connecting factor between these novel applications is the unique interaction of the primary helium ion beam with the sample at and just below its surface. The sub-nanometer sized probe of the 10-35 keV ion beam generates Secondary Electrons (SEs) that have a typical energy between 0 and 20 eV. In most materials, the mean free path of these low-energy SEs is in the order of a few nanometers. Hence the SE signal stems from an area that is very well localized around the point of incidence of the primary beam. This makes the HIM well-suited for both high-resolution imaging as well as high resolution nanofabrication. An extra advantage in nanofabrication is the low ion backscattering fraction, leading to a weak proximity effect. To explore the possibilities of the helium ion microscope as a nanofabrication tool, the HIM at the TNO VLL is equipped with a pattern generator and a gas injection system. This presentation will also touch on the latest lithography results as well as nanostructures made with Helium Ion Beam Induced Processes like deposition and etching. Next to the generation of SEs, used for both imaging and nanofabrication, sample interactions also comprise helium implantation, neutralization, backscattering and some sputtering of target atoms.

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Soft-Lithographic Nanometer-scale Patterning of Functional Oxides
Andre ten Elshof, University of Twente

The soft lithographic techniques are a family of methodologies for the parallel patterning of functional ceramic materials. This contribution discusses recent progress on nanometer-scale patterning of functional ceramics and hybrid organosilicas with resolutions down to 50 nm, including zinc oxide, titania, barium titanate and lead zirconate titanate (PZT).

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A Thin Film Transistor on Poly(Ethylene Naphthalate) Foil using Step-and-Flash Imprint Lithografie
Pieter Moonen, University of Twente

Advanced and flexible organic electronic devices demand high resolution patterning techniques that, for the sake of low-cost fabrication, can be integrated in high throughput manufacturing lines like roll-to-roll (R2R) and roll-to-plate assemblies. The low-cost, alternative lithography technique nanoimprint lithography (NIL)[1] provides high resolution patterning as small as 5 nm[2] combined with short process times. The enhanced functionality of flexible electronic devices (bendable, rollable) combined with low-weight and possible transparency, enables integration into products such as mobile phones, E-readers and thin-film-transistor (TFT) displays. However, the surface flatness and dimensional stability of the flexible substrates needs to be well controlled to obtain good registration accuracy for multi-layer devices, like TFTs. In this paper, the fabrication of flexible thin film transistors (TFTs) on poly(ethylene naphthalate) (PEN) foil in a bottom gate, bottom contact architecture is reported. All functional metal – insulator – metal (MIM) layers are patterned by step-and-flash imprint lithography on the foil, allowing sub-micrometer alignment of the source-drain electrodes to the gate. With the here presented technique, flexible TFTs with channel widths from five micron down to the sub-micrometer regime have been fabricated on PEN foil. The semiconductor, a blend of TIPS pentacene and polystyrene, has been deposited by drop-on-demand inkjet printing. Technology challenges like overlay accuracies, dimensional stability of the flexible substrates and pattern fidelity will be addressed as well In the future, the here developed UV imprint lithography based flexible TFT fabrication process is to be further developed, to allow self-aligned patterning of the source and drain electrodes to the gate; sub-micrometer alignment steps for an good overlay accuracy are not required anymore. The integration into a R2R assembly, to fabricate low cost, high throughput flexible electronic devices is ambitioned.

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Multilayer Extreme UV Optics
Fred Bijkerk, FOM Institute for Plasma Physics Rijnhuizen

Ultrathin layered structures are known to act well as Bragg reflectors for light with wavelengths down to a few nanometers. However, the application of such structures in multi-element optics for photolithography at the wavelength of 13.5 nm has imposed tremendous challenges to the underlying thin film physics. Required is full physical and chemical stability, 10 W/cm2 radiation damage resistance, atomically sharp refractive index profiles, and dimension-controlled thicknesses down to the sub-nanometer range. Layer interdiffusion in the multilayers, for instance, needs to be controlled over pm distances during the typically 30,000 hrs lifetime of the optics. At the top surface of the multilayers, photo-induced chemical phenomena need to be mitigated to avoid even monolayers of contamination during usage of the optics. Pursuing such properties has been the goal of several thin film and optical research programmes, executed in collaboration with end users of the optics. This work has enabled an improved understanding of the basic physics with results immediately being used in state-of-the-art photolithography. An overview will be given of the relevant physics processes as well as the required optics fabrication techniques.

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