Conference program Poster Abstracts
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A facile and efficient method for graphene oxide preparation A novel method for preparing a large scale of graphene oxide based on graphite oxide preparation presented here. Atomic force micrograph (AFM), X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), and Fourier transform infrared (FTIR) analysis methods are used to analyze the Controlling Surface Plasmon Polaritons by Linear Arrays of Metal Nano-Particles well below the diffraction limit, can carry a signal with nearly the speed of light and therefore have a high potential for optoelectronic applications at the Conduction at domain walls in multiferroic BiFeO3 thin films Multiferroics are materials that exhibit simultaneous electric and magnetic order. This confers them great potential for applications such as memories written with electric fields and read with magnetic fields, spin valves operated with electric field or four-state memories. For practical devices, multiferroics are preferred in thin film form. Moreover, the strain induced by the mismatch between the lattice parameters of the film and the substrate can be used to tune and change the film properties with respect to those of the bulk. Unfortunately, multiferroics are rare. The only room temperature, single phase, multiferroic is BiFeO3, an antiferromagnetic and ferroelectric perovskite. BiFeO3 is rhombohedrally distorted with the spontaneous electrical polarization along the [111] direction. There are, thus, four different structural variants present in BiFeO3 leading to eight possible polarization directions (or domains) and three different types of domain walls. Interestingly, the type, density and orientation of the domain walls can be largely controlled by choosing an appropriated substrate. Recent works have shown that the domain walls of BiFeO3 can display promising functionalities different from those of the domains, generating photocurrents and displaying conductivity at room temperature[1]. Using conducting atomic force microscopy as a function of temperature and bias, we have investigated the mechanisms of conduction at domain walls of BiFeO3 thin films grown by pulsed laser deposition. We have observed a selective decrease of the Schottky barrier height (at the interface with the metallic tip) of ~ 2 eV at the domain walls, which clearly enhances the electronic conduction through the walls[2]. This understanding provides the key to control conductivity through nanometers wide domain walls. Graphene: What are the perspectives of the net star in the nanomaterials arena for phovoltaic applications? Graphene is a single layer of carbon atoms in the graphitic structure. This material has made a lot of noise in the scientific community, not only since the AFM Studies of Langmuir Thin Films of Cholesteric Acid deposited on Aluminium substrate Cholesteric Acid molecules form a special class of liquid crystals. These find vital applications in low energy LCDs, Bio-LEDs and thermal detectors. In this paper we have deposited monolayers of Cholesteric Acid molecules on Aluminium substrate and have then characterized the same using Atomic Force Microscope (AFM). The Cholesteric Acid molecules were deposited on smooth Aluminium substrates using the Langmuir Blodgett Thin Film Deposition System at the air-water interface for different surface pressures. The Aluminium substrates were made Hydrophilic by treatment with Piranha Solution (3 parts Conc. H2SO4 and 1 part H202). The deposited films were then studied under Non-Contact Mode of the AFM for different number of layers. Presence of small concentrations of salts (NaOH, ZnSO4 and AlCl3) in the subphase leads to a change in the surface pressure values where the phase change takes place. The Aluminium substrates were found to be very smooth when characterized under AFM and hence the deposited layers could be studied without much topographical disturbances on the substrate surface. We found surprising Spiral-like structures arranged in stacks one above the other on the surface when after characterization under AFM. As the number of layers of Cholesteric Acid was increased, it was found that the arrangement became more and more unordered. Monte-Carlo simulations of electronic processes in a red-emitting multilayer OLED Present-day high-efficiency organic light-emitting diodes (OLEDs) consist of layers of organic semiconductors, where each layer has a specific function. [1] J.J.M. van der Holst, F.W.A. van Oost, R. Coehoorn, P.A. Bobbert, Phys. Rev. B 2011, 83, 085206 Liquid Crystalline Phase Behaviour of Beta-amyloid 1-42 Fibrils The ability to form fibrillar aggregates known as amyloids is inherent to all proteins when partially unfolded, regardless of their native structure, sequence and function. These aggregates display remarkable mechanical properties and are stable under extreme conditions, making them suitable for applications in nanotechnology, where they could be used as supports for nanowires or as scaffolds for biomaterials. Amyloid fibers are chiral structures and according to theoretical studies should exhibit rich liquid crystalline phase behaviour. However, the polymorphism of the fibers makes it difficult to determine the relation between the fiber structure and the macroscopic structure of a fiber network. Here we employ polarization microscopy to quantitatively study the macroscopic phase behaviour of the model peptide Beta Amyloid 1-42 as a function of fiber length, chirality and concentration. In addition we use video particle tracking to study the anisotropic diffusive motion of individual fluorescently labeled fibers embedded in the networks. These experiments and supplementary simulations of chiral rods will provide insight into the physical mechanism governing the phase diagram of the system. Novel Poly(ferrocenylsilane) Based Responsive Hydrogels X. Sui, University of Twente Poly(ferrocenylsilane) – PFS – chains are composed of alternating ferrocene and silane units and can be reversibly oxidized and reduced by chemical or [1] Adv. Mater. 2007, 19, 3439. Nanocomposite Characterization by Differential Scanning Calorimetry Organic and inorganic nanocomposites are generally organic polymer composites with inorganic nanoscale building blocks. They combine the advantages of the inorganic materials (rigidity, thermal stability) and the organic polymer (flexibility, dielectric, ductility, and processability). Moreover, they usually also contain special properties of nanofillers leading to materials with improved properties. A defining feature of polymer nanocomposites is that the small size of the filler leads to a dramatic increase in interfacial area as compared with traditional composites. This interfacial area creates significant volume fraction of interfacial polymer with properties different from the bulk polymer even at low loadings. Inorganic nanoscale building blocks include carbon nanotubes, layered silicates (montnorillonite, saponite), metal nanoparticles (Au, Ag), metal oxide nanoparticles (TiO2, Al2O3), semiconductors (PbS, CdS), and … SiO2. This poster concentrates on the Formulation and End Product validation through Differential Scanning Calorimetry (DSC) characterization. Oriented Llama Antibodies on Tailor-made Surfaces A robust detection method that enables a sensitive and reproducible analysis of targets is the driving force towards biosensors. The on-going miniaturization in this field yields sensors with nanometer-sized dimensions, which limits the size and quantity of deposited detector elements. Llama antibodies are the smallest antibodies available today, and can serve as a detector element for biosensors. Therefore we aim to couple llama antibody domains (VHHs) oriented onto surfaces. VHHs against M. tuberculosis bacterium were selected by means of phage display. The VHHs were produced in E. coli and can be engineered with functional groups, such as an azide (N3), by use of amino acid analogues. An azide can be selectively reacted with an alkyne by Cu(I)-catalyzed Azide-Alkyne 1,3-dipolar Cycloaddition (CuAAC) or Strain promoted Azide-Alkyne 1,3-dipolar Cycloaddition (SPAAC) (see Figure 1). Alkyne terminated surfaces, therefore, can be used to couple VHHs selectively and oriented onto surfaces. Copper as surface for immobilization of the VHHs is appealing for incorporation in CMOS (complementary metal-oxide semiconductor) technology. Copper surfaces were functionalized with thiol-terminated molecules (such as decanethiol or N-succinimidyl mercaptoundecanoate) under argon. These copper-oxide free NHS-ester teminated monolayer are a versatile platform for further functionalization with amine groups yielding tailor-made copper surfaces. Next we aim to immobilize VHHs oriented onto alkyne functionalized surfaces via the azide group. Orientation of VHHs will increase binding efficiency to the target and lower the antigen detection limit. A microreactor as an efficient vehicle to study the regioselective ring opening of epoxides with sodium azide Vicinal azidoalcohols are one of the class of compounds of undoubted interest in organic synthesis1 . The classical protocol uses aqueous solutions of 1M. Pineschi et al. Tetrahedron Lett. 1994, 35, 433. Optimization of micro-reactor settings using integrated optical readout Micro reactors are known for their capability to maintain stable reaction conditions throughout the entire reaction volume. With the right choice of reaction Angle-resolved cathodoluminescence spectroscopy on gold plasmonic nanoresonators We study single crystalline Au ridge resonators, on which a guided surface plasmon polariton (SPP) mode can be excited. The ridge end facets act as mirrors for the SPPs giving the structure Fabry-Pérot type plasmon resonances when an integer number of λspp/2 fits into the length of the resonator [1]. Such a resonator bears many similarities to a metal rod antenna which is known to be an efficient nanoantenna geometry [2]. Resonators with a width of 100 nm, a height of 150 nm and lengths ranging from 100 to 2000 nm were made by milling the inverse structure in a single crystalline gold substrate using focused ion beam milling (FIB) (See Fig 1). We subsequently measured the spectral response and the radiation pattern of these antennas using spatially and angle-resolved cathodoluminescence (CL) spectroscopy. This novel experimental technique combines 10 nm spatial excitation resolution with the ability to collect the radiation pattern. In this experiment we show how it can be used to characterize single nanoantennas without ensemble averaging. For this 700 nm long ridge, we find standing wave resonances for λ=750 nm and λ=600 nm. We clearly distinguish standing wave patterns with 3 and 4 antinodes respectively, corresponding to a λ and 3λ/2 resonance. For these resonances we collected the radiation pattern (Figs. 2-3)) and find that for 750 nm the radiation is emitted in two angular bands, consistent with a linear quadrupole while for 600 nm the radiation is emitted in three bands which is consistent with a linear octupole emission pattern. Electrical Characterization of Multilayered DNA Architectures The preparation of polyelectrolyte multilayers (PEMs) by layer-by-layer (LbL) deposition has proven to be a versatile way of surface modification yielding Optimization of the Lorentz force actuation for a micro Coriolis mass flow sensor We have optimized the Lorentz force actuation of a micromachined Coriolis mass flow sensor. The previously used large permanent magnets resulted in a large sensor and a large magnetic field outside the sensor. The location and size of the permanent magnets has been characterized and optimized using measurements and FEM simulations, resulting in a significant reduction of size of the total sensor as well as reducing the magnetic field outside the chip area by 6 orders of magnitude without reducing the performance of the sensor. Operation principle: The Coriolis mass flow sensor is based on a vibrating tube to measure the Coriolis force as a result of the mass flow through the tube. The tube is being actuated by a Lorentz force caused by an alternating current through a metal track on top of the tube which is in a static magnetic field due to permanent magnets. Figure 1 shows a schematic view of these parameters, Figure 2 shows a photo of the sensor with the previously used permanent magnets. Results: The large magnets of over 500mm2 have been replaced by magnets of only 1mm2. Figure 3 shows simulationresults of the magnetic field of the large(left) and small(mid) magnets. The x-component of the magnetic field of both types of magnets at the metal track on the tube is shown in figure 3(right). The consequences of the change have been characterized using measurements and FEM simulations. These showed a reduction of the magnetic field at the relevant parts of the tube of a factor 1.9±0.3. After correcting the actuation current for the reduced magnetic field, the performance as mass flow sensor has been measured. The results in figure 4 show no deterioration of the performance as sensor. Further characterization of the Lorentz actuation to reduce external influences is being Universal sensor system for the detection of allergens and biomarkers Abstract text Micromachined silicon probes for cochlear auditory nerve stimulation. Cochlear Implant's (CI's) are devices which bypass the non-functional inner ear and directly stimulate the auditory nerve with electric signals thus enabling deaf people to experience speech and other sounds. Devices available in market have limitations such as, experiencing low hearing performance in complex sound environment, causing poor appreciation to music and inability to converse in crowded rooms (cocktail party effect). Also the surgical placement and safe insertion of intracochlear electrodes is complex. The challenge is to deliver more sound details to these electrodes. This research aims towards improving the functionality of CI’s by fabricating electrodes with increased stimulation sites and flexibility to address low frequency sounds and safe insertion to avoid trauma. With silicon micromachining techniques, it should be possible to realize CI electrodes with greater functionality and at lower cost than the manufacturing method used currently. Here we present a silicon micro-machined stiff probe as a roadmap towards the development of future CI electrodes. Stiff probes are to investigate the mechanical stiffness and the stimulation pattern while puncturing the cochlear Universal Scaling of the Figure of Merit of Plasmonic Sensors Metallic nanoparticles are the object of intensive research as they exhibit a characteristic optical response governed by the excitation of localized surface plasmon resonances (LSPRs). Due to the sensitivity of LSPRs to the medium surrounding the nanoparticle, they are of interest for the development of sensitive biochemical sensors employing ultra-small detection volumes. We demonstrate an improvement by more than one order of magnitude of the figure of merit (FoM) of plasmonic nanoparticle sensors by means of the diffractive coupling of localized surface plasmon resonances. The coupling in arrays of nanoparticles leads to Fano resonances with narrow line widths known as surface lattice resonances, which are very suitable for the sensitive detection of small changes in the bulk refractive index of the surroundings. Interestingly, although they can be tuned over a wide spectral range by changing both the lattice constant of the array and the diameter of the particles, we find that the FoM of surface lattice resonances scales ultimately only with the frequency difference between the surface lattice resonance and the diffracted order grazing to the surface of the array. Moreover, we find that this scaling pertains not only to gold nanoparticles, but generally to low loss metals. Such a universal scaling of the FoM does not exist in disordered arrays of nanoparticles, which do not exhibit a collective behaviour. By making an analogy with a model consisting of two linearly coupled harmonic oscillators, we show in a simple manner how the universal scaling law has its origins in the radiative coupling strength of nanoparticles to diffracted orders. High Speed Deflection Detection for Atomic Force Microscopy and Optical Particle Tracking. The time resolution of an Atomic Force Microscope (AFM) to detect cantilever motion, and of an Optical Tweezer (OT) to detect particle motion, is limited by the bandwidth of the optical position detector used. The monolithic Quadrant Photo Diode (QPD) is nowadays the most used detector applied, but, the bandwidth of the fastest QPD system applied in these fields is about 20 MHz [1]. This bandwidth limit is due to the fixed pinout of the QPD and the electronic arithmetic required for the signal conditioning. The 20 MHz limit inhibits the ability to detect higher harmonics from small AFM cantilevers, or to detect any possible fast particle motions in OT. To overcome this limitation we have developed a novel optical beam position detector using discrete photodiodes and optical components [2]. An easy to build experimental detector shows bandwidths in excess of 100 MHz and is shot noise limited. The principle shows to have the potential to detect with multi GHz bandwidths. Using the new detector in AFM or OT systems would enable them to detect the higher harmonics of small cantilevers and to detect particle motions on a much larger bandwidth prospering the exploration of these formerly invisible fields. [1] R. Enning, et. al., Rev. Sci. Instrum. 82. 043705 (2011). Pressure sensor in Silicon On Insulator We report on the fabrication and characterization of a novel type of pressure sensor based on integrated photonic resonators in silicon-on-insulator (SOI) Clinical application of a multimodal nanoparticle; hybrid surgical guidance to the sentinel lymph nodes in prostate cancer patients Introduction: Integration of molecular imaging and in particular intraoperative image guidance is expected to improve the surgical accuracy of laparoscopic Targeted non-covalent self-assembled nanoparticles based on human serum albumin Human serum albumin (HSA) is a biological nanocarrier that forms non-covalent complexes with a number of synthetic and biomolecules. Previously we Tumor bracketing and safety margin estimation using multimodal marker seeds: a proof of concept Accurate tumor excision is crucial in the locoregional treatment of cancer, and for this purpose, surgeons often rely on guide wires or radioactive markers for guidance toward the lesion. Further improvement may be obtained by adding optical guidance to currently used methods, in the form of intraoperative Novel formulations of short chain sphingolipid-enriched liposomal doxorubicin improve drug delivery to tumor cells Entrapment of chemotherapy in liposomal nanocarriers is able to strongly decrease toxic side effects and to increase drug delivery to tumours. Nowadays a liposomal formulation of doxorubicin (Doxil) is available in clinic, however insufficient uptake of chemotherapeutic drugs in tumour cells remains an important limitation in cancer therapy. The aim of this study is to develop optimal liposomal formulations of doxorubicin (Dox) enriched with the short chain spingolipids (SCS) with different hydrophilic headgroups; C8-glucosylceramide (C8-Glucer), C8-galactosylceramide (C8-Galcer) or C8-Lactosylceramide (C8-Lacer) for enhanced intracellular drug delivery. Liposomes were loaded by ammonium sulfate gradient, characterized and stability testing was performed. Afterwards in vitro anti-tumor activity was studied towards a panel of human tumor cell lines and non tumor cells. The intracellular drug uptake was measured by flow cytometry and live cell fluorescence microscopy. In parallel, confocal microscopy was performed to study intracellular fate of liposomes and Dox in living cells. Two optimized formulations of SCS enriched pegylated liposomal doxorubixin (PLD) were identified either containing C8-Glucer or C8-Galcer at a density of 10 mol% and both loaded at a drug to lipid initial ratio of 0.1:1 (w/w). C8-LacCer-enriched PLD was not stable. In all tumor cell lines C8-Glucer or C8-Galcer-PLD exerted increased cytotoxicity, resulting in up to 20 fold lower IC50 values, compared to standard PLD. Strikingly, this effect was not relevant with endothelial cells and fibroblasts. In conclusion, modification of standard PLD formulation with 10% (mol content) of the SCS, C8-Glucer or C8-Galcer can be used to improve intracellular drug delivery and therapeutic efficacy. Smart polymer brush structures for a high throughput membrane protein drug screening assay Macromolecular nanotechnology can be used to develop switchable surfaces, especially so called polymer brushes are suitable for this. Stimulus-responsive polymer brushes grafted from surfaces can be applied for example in biosensors and protein assays. The development of a biosensor for high throughput screening of membrane protein is a major challenge in drug development. Here we present different polymer brush structures, which can be used in such a membrane protein assay. Our aim is to chemically functionalize nanoporous supports so that they can be used as platforms for membrane protein assays. For this we use polymer brushes grafted from surfaces using controlled polymerization techniques, most notably surface-initiated atom transfer radical polymerization (SI-ATRP). These polymer brushes provide robust and reproducible platforms with precise control of surface properties. pH-responsive poly(methacrylic acid) (PMAA) brushes were grafted from nanopore wall surfaces for controlled nanopore sensor function. Opening and closing of the pores were observed in situ by atomic force microscopy (AFM) in liquid environment upon varying the pH of the buffer solution Besides controlled opening and closing of the pores it is also possible to functionalize the carboxylic acid groups of PMAA with nitrilotriacetate (NTA), which can be used as a target for labeled membrane protein. So a membrane protein can be positioned over a nanopore. Another polymer brush structure used in the development of membrane protein assays is poly(2-(N-3-Sulfopropyl-N,N-dimethyl ammonium)ethyl methacrylate) (SBMA), which forms a zwitterionic polymer brush. This polymer brush structure improves conditions for formation of lipid membranes on solid supports. The stability and functionality of supported lipid membranes were probed by various surface sensitive techniques. This research is part of the EU-FP7 project ASMENA “Functional Assays for Membrane Protein on Nanostructured Supports”. Automated monitoring of mycobacterial microcolonies on porous supports for growth detection and drug susceptibility testing Even with the advent of nucleic acid (NA) amplification technologies the culture of mycobacteria for diagnostic and other applications remains of critical Controlled Surface Initiated Polymerizations of PNIPAM on Polymer Substrates Surface initiated polymerizations (SIP), for example using controlled free-radical approaches such as Atom Transfer Radical Polymerization (ATRP) have Hybrid peptide dendrimers for imaging of CXCR4 expression The chemokine receptor 4 (CXCR4), which is over-expressed in many types of cancer, is an emerging target in the field of molecular imaging and Silicon-hydrogel hybrid stamps for multiplexed protein microarrays Protein microarrays have recently gained great interest as they are suited for performing bioanalytical applications such as in vitro diagnostics, proteomics, antibody characterization and drug screening. Ink-jet printing is a commonly used technique to obtain protein microarrays but it is a serial process and does not allow printing of proteins with less than 50 μm resolution. Microarrays with smaller feature sizes are desired as they would allow rapid, highly sensitive, and direct determination of analyte concentration using a small amount of sample. Microcontact printing is a lithography technique that allows parallel arraying of biomolecules over a large surface area with high resolution. It is a low cost, simple and reproducible method but time consuming inking of the stamp is required in each replication step and creating a multiplexed array is still a challenge. In this project, we aim at addressing the multiplexicity and inking challenges of microcontact printing. We present silicon-hydrogel hydbrid stamps having separate ink reservoirs. With this design, multiplexicity can be achieved while avoiding the need for reinking. To prepare the stamps, silicon microstructures having separate wells (320×320 μm) and each well having a 25 μm thick membrane (144 pores measuring 5 μm in diameter) at the bottom were fabricated. Methacryloxypropyl silane functionalised wells allowed covalent binding of macroporous polymethacrylate based hydrogels to the surface of the wells. These hydrogel-filled wells acted as ink reservoir allowing printing of immunoglobulins on polydimethylsiloxane substrates up to 15 times without re-inking. Multiplexed arrays could also be obtained with these stamps by addressing different proteins to separate reservoirs using an inkjet spotter. Probing the initial stages of phagocytosis with magnetic microparticles Circulating monocytes are key blood cells of the innate immune system. In addition, they play an important role in various disorders of the immune system and their functional properties are thought to have diagnostic and predictive value for a variety of diseases. Interaction of myoglobin with oxidized polystyrene surfaces studied with the rotating particles probe The interaction of proteins with polymer surfaces is of profound importance for the sensitivity of biosensors. Polymer surfaces are often treated in order to Carbon nanoparticles as detection label in Lateral Flow-based diagnostics Lateral Flow ImmunoAssays (LFIAs) have an acknowledged position, because they are not only sensitive, but also allow for rapid on-site testing In general, LFIAs are used to detect microorganisms, proteins or chemicals such as antibiotics and mycotoxins. The user-friendliness of its assay format especially qualifies these assays for application under field conditions in resource limited settings. To simplify and speed up analysis of genetic material a one-step assay has been developed that is based on the lateral flow principle and is able to detect PCR-amplified DNA or mRNA in less than 15 minutes. This nucleic acid lateral flow immunoassay (NALFIA) is low-cost and easy to use. The colloidal carbon nanoparticles as used in NALFIA have also been applied as detection labels in microarrays. We have shown that specifically bound carbon nanoparticles can be detected by conventional fladbed scanning followed by image analysis. Combined with dedicated software the dataprocessing of this method can be fully automated. Moreover, in experiments with double-labelled amplicons (comparable to the assay set up of the NALFIA methodology) it has recently been shown that detection of PCR-amplified material is already possible within 60 minutes. In a very recent development the Wageningen group combined the microarray format with the lateral flow principle. This combines the speed and simple performance of the lateral flow assay with the multi-analyte character of the microarray. Interfaces to living cells The field of tissue engineering aims at repairing damaged and/or diseased tissue hoping to reconstitute tissue functionality. Currently, tissue regenerative strategies often revolve around biomaterial scaffolds which serve as a template to guide the tissue regeneration process. Polymeric biomaterials used for these purposes have been selected for their biocompatibility and relative inertness in vivo. This is of great importance since immunological response as well as toxicity must be minimized. Although these materials are well suited to provide mechanical support to the tissue formation process, they do not provoke specific biological actions from the host thus undermining the tissue formation process. A major scientific challenge these days is to modify the material-host interface to interact with the biology and stimulate tissue regeneration. Hence, a lot of effort has been made to develop so-called third generation, instructive materials. Here, cell membrane mimicry is introduced in order to prepare a novel interface to livings cells. In nature, the cell membrane consists of a complex lipid bilayer with integrated proteins essential for cell homeostasis and communication. These proteins are laterally segregated in part by the different phases (lipid rafts) that coexist in a mixed lipid bilayer system. Besides the high degree of self-organization within a lipid bilayer, virtually no protein fouling can occur. This platform, adopted by nature, has great potential to serve as an artificial interface to communicate and interact with cells. Moreover, its self-patterning capacity could be used to yield patterned biomaterial surfaces in complex 3D geometries which are very difficult, if not impossible, to prepare with current technology. In all, mimicking nature’s interface between the extra- and intra cellular domains on biomaterial scaffolds could prove invaluable for Tissue Engineering applications and cell studies. PARALLEL SINGLE CELL ANALYSIS: A POWERFUL TOOL FOR CANCER RESEARCH Parallel single cell analysis (PSCA) is an ideal tool to decipher the relationship between disease development and cellular profile within a cell population. Cell populations are heterogeneous [1] and conventional analysis methods provide averaged data while not revealing any information at the single cell level. However, the analysis of one single cell from a population [2] is biased, and the information cannot be extrapolated to the whole population. Population heterogeneity, which is found in many diseases [3], can be elucidated using a PSCA approach and in the field of cancer research, this approach has tremendous potential for the identification of specific biomarkers and the development of personalized treatments based on individual patient cancer cell profiles. In this study, a 2-layer PDMS microfluidic platform is presented for trapping, lysis and analysis of a large number of individual cells. Single MCF-7 and P3x63Ag8 cells are trapped in a fast, reproducible and automated manner to achieve single cell capture yields of over 90%. In situ cell stimulation and imaging is demonstrated by chemical permeabilization of the plasma membrane using digitonin [4] for the inclusion of foreign materials into each cell. Subsequently, controlled single cell chemical and electrical lysis followed by retrieval of the cellular content into the individual analysis channels using an electroosmotic flow (EOF) is also shown. This step is illustrated with the controlled extraction of calcein out of individual cells. [1] Chao et al.; J. R. Soc. Interface, 2008. Non-fouling and mechaical properties of zwitterionic PSBMA polymer brushes in contact with biomimetic model surfaces grafted from colloidal AFM probes Biofouling is a long-standing issue with tremendous economical and environmental impact. Current scientific research aims at developing novel strategies to design new antifouling surfaces based on protein repellant modifications. Zwitterionic sulfo-betaine polymer brushes are environmentally benign and are promising as ultralow fouling coatings. Based on their unique structure promoting a hydration layer at the brush-water interface, they are protein repellant and effectively suppress biofouling. The ability of poly(sulfobetaine methacrylate) (PSBMA) brushes to resist fouling was assessed by AFM adhesion experiments in contact with a highly adhesive surface. In order to achieve this poly (methyl-methacrylate) (PMAA) brushes were grafted from AFM colloidal gold probes by ATRP, subsequently RGD tripeptide (arginine-lysine-glutamic acid) motifs were covalently attached since it is well known of its role in promoting protein adherence. These probes were used to measure force-distance curves to assess the affinity towards PSBMA brushes grafted from silicon substrates. Neither PMAA nor PMAA-RGD modified surfeces show significant adhesive properties in contact with the PSBMA brush, at pH 7.4 in PBS solution. The measured mean pull-off forces were less than 50 pN but adhesion forces up to 6 nN were detected in case of amine functionalized reference surfaces. The mechanical properties of the different polymer brushes were evaluated from AFM force-distance curves. As the compressibility of the polymer brush depends on the grafting density, corresponding grafting density values were qualitatively estimated from the compression experiments. The obtained values for surface grafted polymer brushes were on the order of 0.11 nm-2. By analyzing the indentation force-distance curves the apparent Young's modulus was obtained. For Si surface grafted PSBMA brush, RGD functionalized PMAA brush and PMAA brush grafted from gold colloid surface 224 ± 12 kPa, 224 ± 6 kPa and 226 ± 8 kPa were obtained, respectively. Langmuir, 23, 2007, 5678 Label-free detection of tuberculosis antigens using a silicon nanowire-based biosensor. Nanowire-based sensing can in principle be developed into a fast, specific and label-free diagnostic device. Nanowires are basically wires with diameters in nanometer range, hence comparable to larger biomolecules such as antibodies or DNA. Due to this decrease in diameter to nano-scale, the ratio of surface atoms compared to interior atoms, i.e. the surface-to-volume ratio, increases. In case of any external influences like charged species, the conduction of electrons through the wire changes, thus making it very sensitive. In the present work we aim for a diagnostic chip based on silicon nanowires modified with highly specific heavy chain llama antibodies for the direct detection of tuberculosis. To first characterize the sensing application, surface plasmon resonance chips were modified with antibodies using biotin-streptavidin interactions and tested against the tuberculosis lysate for direct detection. A maximum binding of 350 R.U. was obtained and the sensitivity of the device was as low as a 0.78ng/μl. This established the sensing concept which will now be extended to the nanowire-based system, where we expect the sensitivity to be higher due to the analogy of nanowires to a serial circuit where interaction at every receptor contributes to the signal. FEM Simulation of PDMS Microfluidics Chamber for Nano Lab-On-Chip Biosensor An important aspect for the realization of a biosensor is the design of the Microfluidics that is needed to deliver the analyte to the sensor surface. Fluidics Quantification of the mix and catch efficiency by microparticles for biosensing with single-molecule resolution Ultra-high-sensitivity affinity assays count target molecules with single-molecule resolution. Such assays are particularly challenging when only few target Glass microfluidic needle arrays for simultaneous neural recording and drug dispensing Introduction. In this work we report on the manufacture of neural recording probes that are made from glass and which are equipped with microfluidic channels for dispensing drugs into the brain during recording sessions. Needle arrays with a length of up to 18 mm were fabricated containing 2 fluidic channels per shaft and 4 recording electrodes distributed along each shaft. Experimental. Glass probes were fabricated by etching microfluidic channels in 100 μm thin glass wafers before bonding a second 100 μm glass wafer. Platinum electrodes were sputtered, patterned and covered with a silicon oxide insulating layer that was etched to expose the metal in order to be able to make a galvanic contact. Finally, the needle shape was etched into the glass substrates from the front and back side simultaneously. Because of the isotropic etching behavior the tip of the needle becomes extremely sharp, reducing the insertion force required to insert the needles into the brain and minimizing the risk of breaking the needles. A flex cable was attached onto the probes using flip-chip bonding technology and four fluidic tubes were glued on. Results and conclusion. The resulting 5-mask assembly was shown to achieve successful electrical contact between the flex cable and the exposed parts of the Platinum electrodes. The correct functioning of the fluidic channels is shown. Liquid jetting for efficient streaming potential energy conversion In this paper, we report a study on the enhancement of microfluidic energy conversion by using a water micro jet technique. Any charged surface accumulates net charges near the surface to form an Electrical Double Layer (EDL). If we apply an external pressure difference over a liquid-filled channel, the net charges will move with the water flow, creating an electrical current (streaming current). By putting two electrodes at the endings of channel, we can pick up the electrical energy. As a result, kinetic energy can be converted into electrical energy. Traditionally, investigators studied the performance of such a fluidic energy conversion system using single phase flow. Recently Duffin and Saykally showed that the efficiency of such a system can be strongly enhanced by having the exiting water forming a jet in air. They didn’t supply a theory for this phenomenon however. In this contribution we strive to provide an explanation. It is known that the conversion efficiency in such systems is limited by a conduction current running in the opposite direction of the streaming current. In previous investigations we showed that interrupting the conduction current by air bubbles strongly increases the conversion efficiency. Here we show that the breakup of the microjet into droplets eliminates the conduction current, explaining the high efficiencies observed. The current measured as a function of height above the receiving reservoir. It can be seen that current strongly depend on the height. This can be explained by the fact that below a height of 3 cm no jet breakup occurred, and hence back conduction could freely occur. Above this height however back conduction was practically eliminated by the droplet breakup, to the extent that 2 nA could be send through a load of 100Gohm, implying a voltage difference of 162 V between both reservoirs. How can soft regulation contribute to responsible nanotechnological development? In the NanoNext programme ‘Anticipation on Embedding of Nanotechnology in Society’ we study the contribution of soft regulation to responsible Do titaniumdioxide (nano)particles pass the intestinal barrier? an in vitro co-culture study Recent developments in nanotechnologies are promising to revolutionise the food and feed sectors. Although the use of engineered nanomaterials in foodproducts is relatively new, such applications are predicted to grow rapidly in the coming years. Currently there are many knowledge gaps related to the toxicokinetics of nanomaterials. In this study we used TiO2 nanoparticles as model compounds to study its potential for passage of the human intestinal barrier. As model for the intestinal barrier we employed an in vitro co-culture in a transwell design, based on CaCo-2 cells and human Raji B lymphocytes. The setup of the system allows a close contact between the 2 cell types triggering the conversion of Caco-2 cells into M-cells. Resulting in a physiologically relevant in vitro model. No translocation of dextrans and lucifer yellow, molecular markers for barrier integrity of the model, was observed. Subsequently the model was exposed for 24 h to a panel of commercial available TiO2 particles: 25 nm, 40 nm, 15x45 nm, 180 nm, <25 nm, <100 nm and <5 micron. These sizes were confirmed by TEM analysis. In cell culture media, the hydrodynamic sizes as determined by Dynamic Light Scattering analysis were between 163-168 nm (25 nm), 131-147 (40 nm), 105-119 (10x45 nm), 493-824 nm (180 nm), 290-363 (<25nm), 500-797 (<100 nm), and 836-870 (<5 micron). A non cyto-toxic dose for TiO2 translocation experiments of 250 μg/ml was established by a WST assay. During exposure, integrity of the cell layer remained intact as determined by TEER measurements. After 24h apical, basolateral and cell samples were subjected to SP-ICPMS analysis. Preliminary data suggest no translocation of the <25 nm, <100 nm and <5 micron TiO2 nanoparticles. The other TiO2 particles are still under SP-ICPMS analysis. These results might imply that these TiO2 nanoparticles do not pass the intestinal barrier Quantifying microparticle-cell binding dynamics and subsequent cell activation The binding interaction between living cells and surfaces is important for a large number of applied and basic scientific disciplines. In cell biology for example, cells need on the one hand to bind to microscopy imaging substrates at which the binding should not trigger undesired cell activation. On the other hand, controlled binding of extracellular objects to cells and measurement of the subsequent cellular responses can reveal novel information about cellular signal processing. A prominent example for a cellular behavior which is triggered by a binding event is phagocytosis. Specialized immune cells such as macrophages use phagocytosis to internalize and degrade bacteria. During phagocytosis, receptors in the macrophage membrane bind to ligands on the bacterium which leads to a wrapping of the macrophage membrane around the bacterium and finally to an internalization of the bacterium into the macrophage. In the past, biology has made great progress in indentifying a large number of molecules that play important roles during phagocytosis. However, little is known about the dynamics of the binding process and the potential immediate cell activation. We study the dynamics of binding and cell activation during phagocytosis by using functionalized microparticles as model systems to mimic bacteria. We bring microparticles in contact with macrophages by using optical tweezers. We detect the Brownian motion of the particles to measure the binding interaction with a temporal resolution on the millisecond time scale. Thereby, the strength of the binding as a function of time is determined with a high temporal resolution. The subsequent immediate cell activation is monitored by live cell light microscopy. Waiting games in the innovation of nanotechnologies and how to deal with them. The development and exploitation of new technologies such as nanotechnologies is associated with expectations about potential benefits, but also with Understanding and supporting responsible development and the introduction of nanotechnologies in society As nanotechnologies are gradually coming out of the laboratory, questions of how nanotechnology enabled applications can be integrated into existing and newly emerging ways of producing, distributing and using such applications, are steadily gaining in importance. Successful innovation, however, comprises more than market success. With increasing concerns over potential health, environmental and safety issues as well as about broader societal impacts of nanotechnologies, the responsible development and introduction of nanotechnologies has become a significant challenge. Exploring potential future directions in innovation and societal embedding processes, then, is important for informing innovation policy and societal strategies as well as orientation of research agendas. Exploring future directions is a challenge in itself considering the uncertainties surrounding nanotechnologies. Therefore we apply thorough analyses and assessment of key dynamics today and tomorrow which build the ground for interactive scenario workshops. Electrochemical Machining: Enabling technology for industrial nanotechnology applications. Introduction [1] A.P. Malshe et all, CIRP Annals - Manufacturing Technology 59 (2010) 628–651 Non-contact Micro-manipulation Systems using Electromagnetic Forces In the current state-of-art technology of automatic micro-manipulation, micro-mechanical manipulator is widely used to handle the object. In practice, the MST Lab&Fab at Fraunhofer IMS Very much since the founding of the institute in the 1980s, Fraunhofer IMS has been pursuing different avenues to add additional value to standard CMOS Fabrication of nano-photonic components on SOI with advanced e-beam lithography We have used an advanced electron-beam lithography tool from Raith for the fabrication of dedicated nano-photonic components such as optical waveguides on silicon-on-insulator platform. Combination of the fixed-beam-moving-stage capabilities, proximity corrected write-field exposure and interferometer laser measurement on the wafers will results in a high fabrication speed with extreme accuracy. Optimization of the complete fabrication process, like the choice of photo resist and specific post-processing steps, simplifies the procedure to get high throughput of complete devices and their components for research goals. All described techniques are also aligned with CMOS mass production procedure which will lead to reduced costs. Self-sustained oscillation of a piezo electric nanomechanical resonator Introduction. Nanoelectromechanical devices (NEMS) have a strong potential as mass, gas and stress sensors. The sensitivity of these devices is determined by their mass, displacement and Q-factor. The Q-factor is an indication of the dissipated energy, increasing the Q-factor leads to a higher accuracy in measurement. In this research we operate a NEMS resonator in a feedback loop. By adjusting the phase lag and the loop gain we can bring the resonator into self-sustained oscillation, which results in an improvement of the Q-factor by one or two orders of magnitude. Devices We use silicon nitride double clamped beams, with an aluminum nitride piezo-electric layer for on-chip actuation, see figure 1. These devices were previously used [1] D.M. Karabacak et al., Enhanced sensitivity volatile detection with low power integrated micromechanical resonators, Lab Chip 10, 1976-1982 (2010) Reflectance Tuning at Extreme Ultraviolet Wavelengths with Active Multilayer Mirrors At extreme ultraviolet (EUV) wavelengths refractive power of transmission type optical components is limited, therefore reflective optics is used. Reflective optics (multilayer mirrors, MLMs) consist of many bilayers and each bilayer is composed of high and low refractive index material. For each bilayer composition reflectance is limited to a range of wavelengths and incidence angles. Here we propose an active MLM structure which can tune its reflectance with external voltage. Active MLM is designed to work at EUV lithography wavelength (13.5 nm) with normal incidence radiation by combining Mo/Si MLMs and a piezoelectric active layer. As the structure and dimensions two Mo/Si MLM stacks are separated by a piezoelectric BaTiO3 layer with SrRuO3 electrodes to apply voltage. Incoming waves will be partially reflected from the upper and the lower MLM stacks. The phase difference between the reflected waves depends on the thickness of the piezoelectric layer which also determines the total reflectance. Reflectance is plotted with respect to thickness of the piezoelectric layer which reaches local minimums and local maximums. Therefore it is possible to change the thickness of the piezoelectric layer by applying voltage to the electrodes which will shift the reflectance to a new value on the reflectance curve. Thickness change is limited by the material and for BaTiO3 it is 4.8% (R. F. Cook, et. al. J. Mater. Res., 1987). As explained in Fig. 1 it is possible to increase the reflectance from Rmin= 60.54% to Rmax= 63.82% by changing the thickness of the piezoelectric layer from zmin= 2.1 nm to zmax= 2.2 nm. In conclusion an active MLM is described for EUV wavelengths that can change its reflectance. Optimization of the structure will be explained in the presentation with possible applications and extensions to different wavelengths. Scattering of Guided Waveguide Modes by Single Plasmonic Structures Controlling, manipulating and reading the state of single quanta of matter using single quanta of light is very interesting not only from a scientific point of view but also for optical applications in new areas such as, for instance, ultra-small detectors, amplifiers and classical and quantum information technology. In order to achieve such control it is necessary to strongly couple light and matter. This process can not be achieved efficiently by simply focusing a beam onto a single emitter due to the limitations set by the diffraction limit and the very small cross sections of single emitters. Therefore a different approach than using focused free space beams is necessary to reach this coupling regime. The cross section of single emitters can be enhanced by using plasmonic nano-antennas which increase the polarizability of the coupled system. Moreover optimized geometries can add directionality to the emitted photons. We expect to be able to use these two effects and achieve close to 100% coupling and detection efficiencies, through the use of Au nano-antennas coupled to the guided modes of 1D and 2D waveguides, which consist of Si3N4 waveguides fabricated on a glass substrate. In this Poster we present the results of our study of transmittance and scattering of guided waveguide modes in 1D and 2D waveguides coupled to single plasmonic structures. The fabricated structures are shown together with simulations based on an in-house written SIE (Surface Integral Equation) method. Optical measurements of the scattering processes of single plasmonic structures are also presented. Wavelength tuning in a photonic crystal micro-cavity by an integrated dielectric micro-cantilever A successful fabrication technique that monolithically integrates a micro-bimorph cantilever equipped with self-aligned tips, with respect to the holes of a photonic crystal micro-cavity based device (PhC-MC), is developed. This technology allows for the fabrication of a new class of devices exploiting modulation of the waveguiding properties of PhC-MCs by changing the proximity of the tips to (and into) the holes of the PhC. The SOI based PhC consists of a line-type cavity (a nine-holes-long section of a channel waveguide), evanescently coupled to two symmetrically arranged line-defect channel waveguides at a distance of three rows of holes. All waveguide sections are of a modified W1 type: one row of holes is omitted from the PhC slab, and the diameters of the boundary holes have been modified in order to fine-tune the optical properties. The integrated bimorph, fabricated by surface micromachining techniques, consists of an upper layer (gold) which acts as the top electrode and a lower layer that acts as a dielectric (silicon rich nitride). Stress, induced by thermal miss-match between the layers and by Frequency conversion and delay using slow light photonic crystal waveguides We use the absorption of an ultrafast (100fs) pump-pulse to dynamically control the frequency and delay of pulses in slow light photonic crystal waveguides. We show here the adiabatic frequency conversion of a light pulse of 0.3THz with 80% conversion efficiency; sufficient for moving a signal over ~10 dense WDM channels. The use of slow-light modes compresses the pulse into a small volume, enabling the entire pulse to be contained in the 20um waveguide when the pump acts. A delay time T after launching a probe-pulse into this mode, the whole waveguide is illuminated by an ultrafast pump-pulse of duration 100fs, leading to an abrupt lowering of the refractive index due to the creation of free electron-hole pairs, blue-shifting the modes of the waveguide by 0.39THz. When the probe pulse is inside the waveguide (at T=0), it is blue-shifted along with the modes. Further, we demonstrate this use of frequency conversion in an optical delay line. If an input signal is shifted in frequency before travelling through a dispersive medium (e.g. from the slow light to the fast light regime of a photonic crystal waveguide), then it will undergo radically different delays. We have fabricated a waveguide designed to achieve this with a relatively small frequency change. In the first 80um, we perform an adiabatic frequency conversion (as described above) – this conversion blue-shifts (by 0.36THz) the pulse from slower modes (ng ~ 23) to faster ones (ng ~ 14) for the remaining 220um (fig. 1(d)). This is equivalent to a photonic indirect transition, but made in two stages. Using this scheme we have demonstrated variable delays greater than 6ps. Near-field investigation of localized modes in slow-light photonic crystal waveguides Disorder in photonic-crystal slab waveguides can cause localization of light [Phys. Rev. Lett. 99, 253901 (2007)]. Sapienza et al. observed that the interaction of localized light with embedded quantum dots is so strong that it yields a considerable Purcell enhancement of the emission rate [Science 327, 1352 (2010)]. This coupling between emitters and these “random cavities” warrants a more detailed investigation. A near-field scanning optical microscope (NSOM) can tap the light from any desired point at the surface of the waveguide with sub-wavelength resolution and is therefore ideally suited to map the spatial distribution of quantum dots, the field distribution of the localized light, as well as the strength of the light-matter interactions. This allows us to extract a wealth of novel optical data. Since the radiative properties of the quantum dots are best at low temperatures, we plan to Improved resolution for soft-x-ray monochromatization using lamellar multilayer amplitude gratings" Lamellar Multilayer Amplitude Gratings (LMAG) offer improved resolution for soft-x-ray (SXR) monochromatization, while maintaining a high reflection efficiency in comparison to conventional multilayer mirrors (MM). Optimal LMAG resolution and reflectivity is obtained for grating periods of only a few hundred nm, lamel widths<100nm and lamel heights>1um [1]. Successful fabrication of such LMAGs, using a novel process based on UV-NanoImprint [1] I.V. Kozhevnikov, R. van der Meer, H.M.J. Bastiaens, K.-J. Boller and F. Bijkerk, Opt. Exp. 18, 16234 (2010) Nanoscale imaging of heterogenous polymers by scanning near-field ellipsometry microscopy Optical microscopy is widely used method to image various materials from synthetic to biological applications. However, the resolution of optical microscopy faces the barrier of the diffraction limit (λ/2). New approaches such as aperture and aperture-less scanning near field optical microscopy (SNOM), stimulated emission depletion fluorescence (STED), photo-activated localization (PALM) and stochastic optical reconstruction (STORM) microscopy were developed to extent optical microscopy beyond the diffraction limit [1, 2]. Nevertheless, widespread application of these techniques has been hampered by some difficulties associated with using tapered fibers, far field background signal, complex instrumentation and sample damage. An alternative approach which can solve some of these problems with a relatively simple instrumentation was proposed [3]. In this experiment an AFM and an ellipsometer were combined for apertureless near-field scanning imaging. In this study, we introduce a simple, non-destructive and economical scanning near-field ellipsometer microscopy (SNEM) setup based on the combination of commercially available AFM and ellipsometer [4]. In our set-up, a sample is placed on a glass substrate and scanned with a gold coated Si AFM tip which is illuminated from below by the laser of an ellipsometer. Near field interactions between the tip and the sample at the highly confined area alter the initially set polarization state of the incident light. This change is then detected at the ellipsometer detector for each scanned point. Films of silver nanoparticles embedded in a poly(methyl methacrylate) (PMMA) matrix and a polystyrene-block-poly(tert-butyl acrylate) PS-b-PtBA diblock copolymer were imaged by using gold and aluminum coated AFM probes. [1] A. Rasmussen, V. Deckert, Anal. Bioanal. Chem., 2005, 381, 165-172. Suppression of Coffee stain effect for nex generation MALDI-MS We study the influence of electrowetting on the formation of undesired solute residues, so-called coffee stains, during the evaporation of a drop containing non-volatile solvents. THe formation of these heterogeneous structures hamper the efficiency of analytical processes in particularly MALDIMS*. Electrowetting is found to suppress coffee stains of both colloidal particles of various sizes and DNA solutions at alternating (AC) frequencies ranging from a few Hertz to a few tens of kHz. Two main effects are shown to contribute to the suppression: (i) the time-dependent electrostatic force prevents pinning of the three phase contact line and (ii) internal flow fields generated by AC electrowetting counteract the evaporation driven flux and thereby prevent the accumulation of solutes along the contact line.Furthermore, we have shown the suppression of Coffee stain effect leads to improved efficiency in MALDI-MS* detection of biomolecules. * MALDI-MS stands for Matrix Asisted Laser Desorption Ionization Mass Spectroscopy. Programmable plasmonic structures for efficient Fluoresence Correlation Spectroscopy We present our work towards programmable plasmonic structures for high resolution adaptive fluorescence correlation spectroscopy. By programmable nanostructures we mean plasmonic structures with different plasmonic eigenmodes, which are designed in such a way, that they exhibit at least two eigenmodes with a large difference in their mode volumes. Furthermore these eigenmodes should be individually excitable by changing the excitation-field properties like polarization, wavelength or wavefront shape. FCS utilizes fluorophores in a solution which diffuse through a confined light field. The time dynamics of the fluorescence signal contains information about the Illuminating the intraflagellar transport machinery in the sensory cilia of Caenorhabditis elegans Inside cells molecular motors of the kinesin and dynein superfamilies orchestrate vital processes, such as cell division, cell propulsion and intracellular transport. In particular in neurons, with their extensive processes, motor proteins are of key importance to drive constant and fast transport of proteins, vesicles and organelles to and from the cell extremities. In Caenorhabditis elegans the denditric endings of its chemosensory neurons are connected to the outside world via sensory cilia. Within the sensory cilium two kinesin-2-family motors, heterotrimeric kinesin-II and homodimeric OSM-3-kinesin, are responsible for building and maintaining the cilium structure, in a process called intraflagellar transport (IFT). These two IFT kinesins cooperate to provide the anterograde transport along the doublet microtubles (MTs), however, OSM-3-kinesin alone maintains the distal segment that consists of singlet MTs. Another type of motor, IFT-dynein, provides the retrograde transport from the cilium tip to the basal body thereby recycling the IFT machinery. It is unknown how these motors collaborate to drive IFT and form and maintain cilia. Our goal is to unravel, on the molecular level using ultrasensitive fluorescence microscopy, how the motors cooperate and how transport is related to human diseases caused by genetic defects in the IFT machinery such as polycystic kidney disease (PKD). In order to study IFT on the single-molecule level numerous challenges such as a high autofluorescent background have to be overcome. Therefore, we are developing new microscopy techniques to obtain the temporal resolution and spatial precision necessary. Together with Mos1 mediated single-copy integration of transgenes that encode for fluorescently-labeled-IFT motors we set out to count, track and map these molecular machines at endogenous expression levels. This application of single-molecule techniques in vivo holds great promise to provide new insights into IFT and other motor-driven Particle detection on flat surfaces Since 2006, EUV Lithographic tools have been available for testing purposes. This gave a boost to the development of fab infrastructure for EUV masks. The absence of a pellicle makes the EUV reticles extremely vulnerable to particles. Therefore, the fab infrastructure for masks must meet very strict particle requirements. It is expected that all new equipment must be qualified on particles before it can be put into operation. This qualification requirement increases the need for a low cost method for particle detection on mask substrates. TNO developed its fourth generation particle scanner, the Nano Particle Scanner. The Nano Particle Scanner is capable of detecting nm sized particles on flat surfaces. The detection is based on dark field imaging techniques and fast image processing. The tool was designed for detection of a single added particle in a handling experiment over a reticle sized substrate. Therefore, this tool is very suitable for the validation of particle cleanliness of equipment. During the measurement, the substrates are protected against particle contamination by using a protective environment. All stages and other possible particle sources are placed outside the protective environment. The imaging takes place through a window. The geometry of the protective environment enables large flexibility in substrate shape and size. Particles can be detected on substrates varying from 152 x 152 mm mask substrates to wafers with a diameter up to 150 mm. Programmed chromium defects on silicon were used for determination of the sensitivity of the Nano Particle Scanner. Particles of 55 nm and larger were observed on a detectable level. Results on capture efficiency for particles in the range between 30 nm and 400 nm according to the standard SEMI M50-0307 will be presented. |