Search results for: segmented chip

Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: Khyamling Parane, B. M. Prabhu Prasad, Basavaraj Talawar

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Fast simulations are critical in reducing time to market in CMPs and SoCs. Several simulators have been used to evaluate the performance and power consumed by Network-on-Chips. Researchers and designers rely upon these simulators for design space exploration of NoC architectures. Our experiments show that simulating large NoC topologies take hours to several days for completion. To speed up the simulations, it is necessary to investigate and optimize the hotspots in simulator source code. Among several simulators available, we choose Booksim2.0, as it is being extensively used in the NoC community. In this paper, we analyze the cache and memory system behaviour of Booksim2.0 to accurately monitor input dependent performance bottlenecks. Our measurements show that cache and memory usage patterns vary widely based on the input parameters given to Booksim2.0. Based on these measurements, the cache configuration having least misses has been identified. To further reduce the cache misses, we use software optimization techniques such as removal of unused functions, loop interchanging and replacing post-increment operator with pre-increment operator for non-primitive data types. The cache misses were reduced by 18.52%, 5.34% and 3.91% by employing above technology respectively. We also employ thread parallelization and vectorization to improve the overall performance of Booksim2.0. The OpenMP programming model and SIMD are used for parallelizing and vectorizing the more time-consuming portions of Booksim2.0. Speedups of 2.93x and 3.97x were observed for the Mesh topology with 30 × 30 network size by employing thread parallelization and vectorization respectively.

Keywords: cache behaviour, network-on-chip, performance profiling, vectorization

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Authors: Sridhar A. Malkaram, Tamer E. Fandy

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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.

Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics

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Authors: Mrinalini Amritkar, Disha Patil, Swapna Kulkarni, Sukratu Barve, Suresh Gosavi

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Micro-mixers play an important role in the lab-on-a-chip applications and micro total analysis systems to acquire the correct level of mixing for any given process. The mixing process can be classified as active or passive according to the use of external energy. Literature of microfluidics reports that most of the work is done on the models of steady laminar flow; however, the study of unsteady laminar flow is an active area of research at present. There are wide applications of this, out of which, we consider nanoparticle synthesis in micro-mixers. In this work, we have developed a model for unsteady flow to study the mixing performance of a passive micro mixer for reactants used for such synthesis. The model is developed in Finite Volume Method (FVM)-based software, OpenFOAM. The model is tested by carrying out the simulations at Re of 0.5. Mixing performance of the micro-mixer is investigated using simulated concentration values of mixed species across the width of the micro-mixer and calculating the variance across a line profile. Experimental validation is done by passing dyes through a Y shape micro-mixer fabricated using polydimethylsiloxane (PDMS) polymer and comparing variances with the simulated ones. Gold nanoparticles are later synthesized through the micro-mixer and collected at two different times leading to significantly different size distributions. These times match with the time scales over which reactant concentrations vary as obtained from simulations. Our simulations could thus be used to create design aids for passive micro-mixers used in nanoparticle synthesis.

Keywords: Lab-on-chip, LOC, micro-mixer, OpenFOAM, PDMS

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Authors: S. Thomet, S. De-Paoli, F. Ghaffari, J. M. Daveau, P. Roche, O. Romain

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In this paper, we present a hardware module dedicated to understanding the fail reason of a System on Chip (SoC) exposed to a particle beam. Impact of Single-Event Effects (SEE) on processor-based SoCs is a concern that has increased in the past decade, particularly for terrestrial applications with automotive safety increasing requirements, as well as consumer and industrial domains. The SEE created by the impact of a particle on an SoC may have consequences that can end to instability or crashes. Specific hardening techniques for hardware and software have been developed to make such systems more reliable. SoC is then qualified using cosmic ray Accelerated Soft-Error Rate (ASER) to ensure the Soft-Error Rate (SER) remains in mission profiles. Understanding where errors are occurring is another challenge because of the complexity of operations performed in an SoC. Common techniques to monitor an SoC running under a beam are based on non-intrusive debug, consisting of recording the program counter and doing some consistency checking on the fly. To detect and understand SEE, we have developed a module embedded within the SoC that provide support for recording probes, hardware watchpoints, and a memory mapped register bank dedicated to software usage. To identify CPU failure modes and the most important resources to probe, we have carried out a fault injection campaign on the RTL model of the SoC. Probes are placed on generic CPU registers and bus accesses. They highlight the propagation of errors and allow identifying the failure modes. Typical resulting errors are bit-flips in resources creating bad addresses, illegal instructions, longer than expected loops, or incorrect bus accesses. Although our module is processor agnostic, it has been interfaced to a RISC-V by probing some of the processor registers. Probes are then recorded in a ring buffer. Associated hardware watchpoints are allowing to do some control, such as start or stop event recording or halt the processor. Finally, the module is also providing a bank of registers where the firmware running on the SoC can log information. Typical usage is for operating system context switch recording. The module is connected to a dedicated debug bus and is interfaced to a remote controller via a debugger link. Thus, a remote controller can interact with the monitoring module without any intrusiveness on the SoC. Moreover, in case of CPU unresponsiveness, or system-bus stall, the recorded information can still be recovered, providing the fail reason. A preliminary version of the module has been integrated into a test chip currently being manufactured at ST in 28-nm FDSOI technology. The module has been triplicated to provide reliable information on the SoC behavior. As the primary application domain is automotive and safety, the efficiency of the module will be evaluated by exposing the test chip under a fast-neutron beam by the end of the year. In the meantime, it will be tested with alpha particles and electromagnetic fault injection (EMFI). We will report in the paper on fault-injection results as well as irradiation results.

Keywords: fault injection, SoC fail reason, SoC soft error rate, terrestrial application

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Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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Authors: Su Chul Han, Seungwoo Park

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As the increasing incidence of cancer, the technology and modality of radiotherapy have advanced and the importance of preclinical model is increasing in the cancer research. Furthermore, the small animal dosimetry is an essential part of the evaluation of the relationship between the absorbed dose in preclinical small animal and biological effect in preclinical study. In this study, we carried out realistic modeling of the preclinical small animal phantom possible to verify irradiated dose using commercial software. The small animal phantom was modeling from 4D Digital Mouse whole body phantom. To manipulate Moby phantom in commercial software (Mimics, Materialise, Leuven, Belgium), we converted Moby phantom to DICOM image file of CT by Matlab and two- dimensional of CT images were converted to the three-dimensional image and it is possible to segment and crop CT image in Sagittal, Coronal and axial view). The CT images of small animals were modeling following process. Based on the profile line value, the thresholding was carried out to make a mask that was connection of all the regions of the equal threshold range. Using thresholding method, we segmented into three part (bone, body (tissue). lung), to separate neighboring pixels between lung and body (tissue), we used region growing function of Mimics software. We acquired 3D object by 3D calculation in the segmented images. The generated 3D object was smoothing by remeshing operation and smoothing operation factor was 0.4, iteration value was 5. The edge mode was selected to perform triangle reduction. The parameters were that tolerance (0.1mm), edge angle (15 degrees) and the number of iteration (5). The image processing 3D object file was converted to an STL file to output with 3D printer. We modified 3D small animal file using 3- Matic research (Materialise, Leuven, Belgium) to make space for radiation dosimetry chips. We acquired 3D object of realistic small animal phantom. The width of small animal phantom was 2.631 cm, thickness was 2.361 cm, and length was 10.817. Mimics software supported efficiency about 3D object generation and usability of conversion to STL file for user. The development of small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

Keywords: mimics, preclinical small animal, segmentation, 3D printer

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Authors: Mohit Modi, Rajiv Kumar, Manojraj Saxena, G. Ravi Shankar

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Change detection of coastal ecosystem plays a vital role in monitoring and managing natural resources along the coastal regions. The present study mainly focuses on the decadal change in Kochi islands connecting the urban flatland areas and the coastal regions where sand deposits have taken place. With this, in view, the change detection has been monitored in the Kochi area to apprehend the urban growth and industrialization leading to decrease in the wetland ecosystem. The region lies between 76°11'19.134"E to 76°25'42.193"E and 9°52'35.719"N to 10°5'51.575"N in the south-western coast of India. The IRS LISS-IV satellite image has been processed using a rule-based algorithm to classify the LULC and to interpret the changes between 2005 & 2015. The approach takes two steps, i.e. extracting features as a single GIS vector layer using different parametric values and to dissolve them. The multi-resolution segmentation has been carried out on the scale ranging from 10-30. The different classes like aquaculture, agricultural land, built-up, wetlands etc. were extracted using parameters like NDVI, mean layer values, the texture-based feature with corresponding threshold values using a rule set algorithm. The objects obtained in the segmentation process were visualized to be overlaying the satellite image at a scale of 15. This layer was further segmented using the spectral difference segmentation rule between the objects. These individual class layers were dissolved in the basic segmented layer of the image and were interpreted in vector-based GIS programme to achieve higher accuracy. The result shows a rapid increase in an industrial area of 40% based on industrial area statistics of 2005. There is a decrease in wetlands area which has been converted into built-up. New roads have been constructed which are connecting the islands to urban areas as well as highways. The increase in coastal region has been visualized due to sand depositions. The outcome is well supported by quantitative assessments which will empower rich understanding of land use land cover change for appropriate policy intervention and further monitoring.

Keywords: land use land cover, multiresolution segmentation, NDVI, object based classification

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Authors: Jorge Prada, Christina Cordes, Carsten Harms, Walter Lang

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The development of microfluidic-based biosensors over the last years has shown an increasing employ of thermoplastic polymers as constitutive material. Their low-cost production, high replication fidelity, biocompatibility and optical-mechanical properties are sought after for the implementation of disposable albeit functional lab-on-chip solutions. Among the range of thermoplastic materials on use, the Cyclo-Olefin Copolymer (COC) stands out due to its optical transparency, which makes it a frequent choice as manufacturing material for fluorescence-based biosensors. Moreover, several processing techniques to complete a closed COC microfluidic biosensor have been discussed in the literature. The reported techniques differ however in their implementation, and therefore potentially add more or less complexity when using it in a mass production process. This work introduces and reports results on the application of a purely thermal bonding process between COC substrates, which were produced by the hot-embossing process, and COC foils containing screen-printed circuits. The proposed procedure takes advantage of the transition temperature difference between two COC grades foils to accomplish the sealing of the microfluidic channels. Patterned heat injection to the COC foil through the COC substrate is applied, resulting in consistent channel geometry uniformity. Measurements on bond strength and bursting pressure are shown, suggesting that this purely thermal bonding process potentially renders a technique which can be easily adapted into the thermoplastic microfluidic chip production workflow, while enables a low-cost as well as high-quality COC biosensor manufacturing process.

Keywords: biosensor, cyclo-olefin copolymer, hot embossing, thermal bonding, thermoplastics

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Authors: Manel Langar, Riad Bourguiba, Jaouhar Mouine

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In this paper, we propose the design and implementation of an enhanced wormhole virtual channel on chip router. It is a heart of a mesh NoC using the XY deterministic routing algorithm. It is characterized by its simple virtual channel allocation strategy which allows reducing area and complexity of connections without affecting the performance. We implemented our router on a Tezzaron process to validate its performances. This router is a basic element that will be used later to design a 3D mesh NoC.

Keywords: NoC, mesh, router, 3D NoC

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Authors: Feng-Hisang Lai

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CFD(Computational Fluid Dynamics) is conducted to numerically study the flow and heat transfer features of a two-pole, 6,080HP, 60Hz, 3,150V open drip-proof (ODP) motor. The stator and rotor cores in this high voltage induction motor are segmented with the use of spacers for cooling purposes, which leads to difficulties in meshing when the entire system is to be simulated. The system is divided into 4 parts, meshed separately and then combined using interfaces. The deviation between the CFD and experimental results in temperature and flow rate is less than 10%. The internal flow is further examined and a final design is proposed to reduce the winding temperature by 10 degrees.

Keywords: CFD, open drip proof, induction motor, cooling

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Authors: G. C. Santini, C. Potrich, L. Lunelli, L. Vanzetti, S. Marasso, M. Cocuzza, C. Pederzolli

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The relevance of circulating miRNAs as non-invasive biomarkers for several pathologies is nowadays undoubtedly clear, as they have been found to have both diagnostic and prognostic value able to add fundamental information to patients’ clinical picture. The availability of these data, however, relies on a time-consuming process spanning from the sample collection and processing to the data analysis. In light of this, strategies which are able to ease this procedure are in high demand and considerable effort have been made in developing Lab-on-a-chip (LOC) devices able to speed up and standardise the bench work. In this context, a very promising polydimethylsiloxane (PDMS)-based microdevice which integrates the processing of the biological sample, i.e. purification of extracellular miRNAs, and reverse transcription was previously developed in our lab. In this study, we aimed at the improvement of the miRNA extraction performances of this micro device by increasing the ability of its surface to absorb extracellular miRNAs from biological samples. For this purpose, we focused on the modulation of two properties of the material: roughness and charge. PDMS surface roughness was modulated by casting with several templates (terminated with silicon oxide coated by a thin anti-adhesion aluminum layer), followed by a panel of curing conditions. Atomic force microscopy (AFM) was employed to estimate changes at the nanometric scale. To introduce modifications in surface charge we functionalized PDMS with different mixes of positively charged 3-aminopropyltrimethoxysilanes (APTMS) and neutral poly(ethylene glycol) silane (PEG). The surface chemical composition was characterized by X-ray photoelectron spectroscopy (XPS) and the number of exposed primary amines was quantified with the reagent sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate (s-SDTB). As our final end point, the adsorption rate of all these different conditions was assessed by fluorescence microscopy by incubating a synthetic fluorescently-labeled miRNA. Our preliminary analysis identified casting on thermally grown silicon oxide, followed by a curing step at 85°C for 1 hour, as the most efficient technique to obtain a PDMS surface roughness in the nanometric scaleable to trap miRNA. In addition, functionalisation with 0.1% APTMS and 0.9% PEG was found to be a necessary step to significantly increase the amount of microRNA adsorbed on the surface, therefore, available for further steps as on-chip reverse transcription. These findings show a substantial improvement in the extraction efficiency of our PDMS microdevice, ultimately leading to an important step forward in the development of an innovative, easy-to-use and integrated system for the direct purification of less abundant circulating microRNAs.

Keywords: circulating miRNAs, diagnostics, Lab-on-a-chip, polydimethylsiloxane (PDMS)

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Authors: F. Rarbi, D. Dzahini, W. Uhring

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In this paper, a dynamic and power efficient 8-bit and 100-MSPS Successive Approximation Register (SAR) Analog-to-Digital Converter (ADC) is presented. The circuit uses a non-differential capacitive Digital-to-Analog (DAC) architecture segmented by 2. The prototype is produced in a commercial 65-nm 1P7M CMOS technology with 1.2-V supply voltage. The size of the core ADC is 208.6 x 103.6 µm². The post-layout noise simulation results feature a SNR of 46.9 dB at Nyquist frequency, which means an effective number of bit (ENOB) of 7.5-b. The total power consumption of this SAR ADC is only 1.55 mW at 100-MSPS. It achieves then a figure of merit of 85.6 fJ/step.

Keywords: CMOS analog to digital converter, dynamic comparator, image sensor application, successive approximation register

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Authors: Zahrasadat Hosseini, Jie Yuan

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Point-of-care (POC) diagnostic devices based on lab-on-a-chip (LOC) technology have the potential to revolutionize medical diagnostics. However, the development of an ideal microfluidic system based on LOC technology for diagnostics purposes requires overcoming several obstacles, such as improving sensitivity, selectivity, portability, cost-effectiveness, and prototyping methods. While numerous studies have introduced technologies and systems that advance these criteria, existing systems still have limitations. Electrochemical enzyme-linked immunosorbent assay (e-ELISA) in a LOC device offers numerous advantages, including enhanced sensitivity, decreased turnaround time, minimized sample and analyte consumption, reduced cost, disposability, and suitability for miniaturization, integration, and multiplexing. In this study, we present a novel design and fabrication method for a microfluidic diagnostic platform that integrates screen-printed electrochemical carbon/silver chloride electrodes on flexible printed circuit boards with flexible, multilayer, polydimethylsiloxane (PDMS) microfluidic networks to accurately manipulate and pre-immobilize analytes for performing electrochemical enzyme-linked immunosorbent assay (e-ELISA) for multiplexed quantification of blood serum biomarkers. We further demonstrate fast, cost-effective prototyping, as well as accurate and reliable detection performance of this device for quantification of interleukin-6-spiked samples through electrochemical analytics methods. We anticipate that our invention represents a significant step towards the development of user-friendly, portable, medical-grade, POC diagnostic devices.

Keywords: lab-on-a-chip, point-of-care diagnostics, electrochemical ELISA, biomarker quantification, fast prototyping

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Authors: Zahrasadat Hosseini, Jie Yuan

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Point-of-care (POC) diagnostic devices based on lab-on-a-chip (LOC) technology have the potential to revolutionize medical diagnostics. However, the development of an ideal microfluidic system based on LOC technology for diagnostics purposes requires overcoming several obstacles, such as improving sensitivity, selectivity, portability, cost-effectiveness, and prototyping methods. While numerous studies have introduced technologies and systems that advance these criteria, existing systems still have limitations. Electrochemical enzyme-linked immunosorbent assay (e-ELISA) in a LOC device offers numerous advantages, including enhanced sensitivity, decreased turnaround time, minimized sample and analyte consumption, reduced cost, disposability, and suitability for miniaturization, integration, and multiplexing. In this study, we present a novel design and fabrication method for a microfluidic diagnostic platform that integrates screen-printed electrochemical carbon/silver chloride electrodes on flexible printed circuit boards with flexible, multilayer, polydimethylsiloxane (PDMS) microfluidic networks to accurately manipulate and pre-immobilize analytes for performing electrochemical enzyme-linked immunosorbent assay (e-ELISA) for multiplexed quantification of blood serum biomarkers. We further demonstrate fast, cost-effective prototyping, as well as accurate and reliable detection performance of this device for quantification of interleukin-6-spiked samples through electrochemical analytics methods. We anticipate that our invention represents a significant step towards the development of user-friendly, portable, medical-grade POC diagnostic devices.

Keywords: lab-on-a-chip, point-of-care diagnostics, electrochemical ELISA, biomarker quantification, fast prototyping

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Authors: Bo Liu, Chi-Man Pun

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A novel technique for digital forgery detection by signal noise inconsistency is proposed in this paper. The forged area spliced from the other picture contains some features which may be inconsistent with the rest part of the image. Noise pattern and the level is a possible factor to reveal such inconsistency. To detect such noise discrepancies, the test picture is initially segmented into small pieces. The noise pattern and level of each segment are then estimated by using various filters. The noise features constructed in this step are utilized in energy-based graph cut to expose forged area in the final step. Experimental results show that our method provides a good illustration of regions with noise inconsistency in various scenarios.

Keywords: forgery detection, splicing forgery, noise estimation, noise

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Authors: Mohammadreza Hedyehzadeh, Mahdi Yousefi

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Colon cancer is one of the most common cancer, which predicted to increase its prevalence due to the bad eating habits of peoples. Nowadays, due to the busyness of people, the use of fast foods is increasing, and therefore, diagnosis of this disease and its treatment are of particular importance. To determine the best treatment approach for each specific colon cancer patients, the oncologist should be known the stage of the tumor. The most common method to determine the tumor stage is TNM staging system. In this system, M indicates the presence of metastasis, N indicates the extent of spread to the lymph nodes, and T indicates the size of the tumor. It is clear that in order to determine all three of these parameters, an imaging method must be used, and the gold standard imaging protocols for this purpose are CT and PET/CT. In CT imaging, due to the use of X-rays, the risk of cancer and the absorbed dose of the patient is high, while in the PET/CT method, there is a lack of access to the device due to its high cost. Therefore, in this study, we aimed to estimate the tumor size and the extent of its spread to the lymph nodes using MR images. More than 1300 MR images collected from the TCIA portal, and in the first step (pre-processing), histogram equalization to improve image qualities and resizing to get the same image size was done. Two expert radiologists, which work more than 21 years on colon cancer cases, segmented the images and extracted the tumor region from the images. The next step is feature extraction from segmented images and then classify the data into three classes: T0N0، T3N1 و T3N2. In this article, the VGG-16 convolutional neural network has been used to perform both of the above-mentioned tasks, i.e., feature extraction and classification. This network has 13 convolution layers for feature extraction and three fully connected layers with the softmax activation function for classification. In order to validate the proposed method, the 10-fold cross validation method used in such a way that the data was randomly divided into three parts: training (70% of data), validation (10% of data) and the rest for testing. It is repeated 10 times, each time, the accuracy, sensitivity and specificity of the model are calculated and the average of ten repetitions is reported as the result. The accuracy, specificity and sensitivity of the proposed method for testing dataset was 89/09%, 95/8% and 96/4%. Compared to previous studies, using a safe imaging technique (MRI) and non-use of predefined hand-crafted imaging features to determine the stage of colon cancer patients are some of the study advantages.

Keywords: colon cancer, VGG-16, magnetic resonance imaging, tumor size, lymph node metastasis

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Authors: Manon Giraud, Francois-Damien Delapierre, Guenaelle Jasmin-Lebras, Cecile Feraudet-Tarisse, Stephanie Simon, Claude Fermon

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Early diagnosis or detection of harmful substances at low level is a growing field of high interest. The ideal test should be cheap, easy to use, quick, reliable, specific, and with very low detection limit. Combining the high specificity of antibodies-functionalized magnetic beads used to immune-capture biologic objects and the high sensitivity of a GMR-based sensors, it is possible to even detect these biologic objects one by one, such as a cancerous cell, a bacteria or a disease biomarker. The simplicity of the detection process makes its use possible even for untrained staff. Giant Magneto Resistance (GMR) is a recently discovered effect consisting in the electrical resistance modification of some conductive layers when exposed to a magnetic field. This effect allows the detection of very low variations of magnetic field (typically a few tens of nanoTesla). Magnetic nanobeads coated with antibodies targeting the analytes are mixed with a biological sample (blood, saliva) and incubated for 45 min. Then the mixture is injected in a very simple microfluidic chip and circulates above a GMR sensor that detects changes in the surrounding magnetic field. Magnetic particles do not create a field sufficient to be detected. Therefore, only the biological objects surrounded by several antibodies-functionalized magnetic beads (that have been captured by the complementary antigens) are detected when they move above the sensor. Proof of concept has been carried out on NS1 mouse cancerous cells diluted in PBS which have been bonded to magnetic 200nm particles. Signals were detected in cells-containing samples while none were recorded for negative controls. Binary response was hence assessed for this first biological model. The precise quantification of the analytes and its detection in highly diluted solution is the step now in progress.

Keywords: early diagnosis, giant magnetoresistance, lab-on-a-chip, submicron particle

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Authors: Moustafa Osman Mohammed

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This paper introduces Luhmann’s autopoietic social systems starting with the original concept of autopoiesis by biologists and scientists, including the modification of general systems based on socialized medicine. A specific type of autopoietic system is explained in the three existing groups of the ecological phenomena: interaction, social and medical sciences. This hypothesis model, nevertheless, has a nonlinear interaction with its natural environment ‘interactional cycle’ for the exchange of photon energy with molecular without any changes in topology. The external forces in the systems environment might be concomitant with the natural fluctuations’ influence (e.g. radioactive radiation, electromagnetic waves). The cantilever sensor deploys insights to the future chip processor for prevention of social metabolic systems. Thus, the circuits with resonant electric and optical properties are prototyped on board as an intra–chip inter–chip transmission for producing electromagnetic energy approximately ranges from 1.7 mA at 3.3 V to service the detection in locomotion with the least significant power losses. Nowadays, therapeutic systems are assimilated materials from embryonic stem cells to aggregate multiple functions of the vessels nature de-cellular structure for replenishment. While, the interior actuators deploy base-pair complementarity of nucleotides for the symmetric arrangement in particular bacterial nanonetworks of the sequence cycle creating double-stranded DNA strings. The DNA strands must be sequenced, assembled, and decoded in order to reconstruct the original source reliably. The design of exterior actuators have the ability in sensing different variations in the corresponding patterns regarding beat-to-beat heart rate variability (HRV) for spatial autocorrelation of molecular communication, which consists of human electromagnetic, piezoelectric, electrostatic and electrothermal energy to monitor and transfer the dynamic changes of all the cantilevers simultaneously in real-time workspace with high precision. A prototype-enabled dynamic energy sensor has been investigated in the laboratory for inclusion of nanoscale devices in the architecture with a fuzzy logic control for detection of thermal and electrostatic changes with optoelectronic devices to interpret uncertainty associated with signal interference. Ultimately, the controversial aspect of molecular frictional properties is adjusted to each other and forms its unique spatial structure modules for providing the environment mutual contribution in the investigation of mass temperature changes due to pathogenic archival architecture of clusters.

Keywords: autopoiesis, nanoparticles, quantum photonics, portable energy, photonic structure, photodynamic therapeutic system

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Authors: Rina Lee, Chung-Hun Oh, Eunjin Lee, Jeongyun Kim

Abstract:

The Photodynamic therapy (PDT) is a treatment that uses a photosensitizer as a drug to damage and kill cancer cells. After injecting the photosensitizer into the bloodstream, the drug is absorbed by cancer cells selectively. Then the area to be treated is exposed to specific wavelengths of light and the photosensitizer produces a form of oxygen that kills nearby cancer cells. PDT is has an advantage to destroy the tumor with minimized side-effects on normal cells. But, PDT is not a completed method for cancer therapy. Because the mechanism of PDT is quite clear yet and the parameters such as intensity of light and dose of photosensitizer are not optimized for different types of cancers. To optimize these parameters, we suggest a novel microfluidic system to automatically control intensity of light exposure with a personal computer (PC). A polydimethylsiloxane (PDMS) microfluidic chip is composed with (1) a cell culture channels layer where cancer cells were trapped to be tested with various dosed photofrin (1μg/ml used for the test) as the photosensitizer and (2) a color dye layer as a neutral density (ND) filter to reduce intensity of light which exposes the cell culture channels filled with cancer cells. Eight different intensity of light (10%, 20%, …, 100%) are generated through various concentrations of blue dye filling the ND filter. As a light source, a light emitting diode (LED) with 635nm wavelength was placed above the developed PDMS microfluidic chip. The total time for light exposure was 30 minutes and HeLa and PC3 cell lines of cancer cells were tested. The cell viability of cells was evaluated with a Live/Dead assay kit (L-3224, Invitrogen, USA). The stronger intensity of light exposed, the lower viability of the cell was observed, and vice versa. Therefore, this system was demonstrated through investigating the PDT against cancer cell to optimize the parameters as critical light intensity and dose of photosensitizer. Our results suggest that the system can be used for optimizing the combinational parameters of light intensity and photosensitizer dose against diverse cancer cell types.

Keywords: photodynamic therapy, photofrin, high throughput screening, hela

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Authors: Varun A Baheti, Sanjay Kashyap, Kamanio Chattopadhyay, Praveen Kumar, Aloke Paul

Abstract:

Ni–Sn system finds applications in the microelectronics industry, especially with respect to flip–chip or direct chip, attach technology. Here the region of interest is under bump metallization (UBM), and solder bump (Sn) interface due to the formation of brittle intermetallic phases there. Understanding the growth of these phases at UBM/Sn interface is important, as in many cases it controls the electro–mechanical properties of the product. Cu and Ni are the commonly used UBM materials. Cu is used for good bonding because of fast reaction with solder and Ni often acts as a diffusion barrier layer due to its inherently slower reaction kinetics with Sn–based solders. Investigation on the growth kinetics of phases in Ni–Sn system is reported in this study. Just for simplicity, Sn being major solder constituent is chosen. Ni–Sn electroplated diffusion couples are prepared by electroplating pure Sn on Ni substrate. Bulk diffusion couples prepared by the conventional method are also studied along with Ni–Sn electroplated diffusion couples. Diffusion couples are annealed for 25–1000 h at 50–215°C to study the phase evolutions and growth kinetics of various phases. The interdiffusion zone was analysed using field emission gun equipped scanning electron microscope (FE–SEM) for imaging. Indexing of selected area diffraction (SAD) patterns obtained from transmission electron microscope (TEM) and composition measurements done in electron probe micro−analyser (FE–EPMA) confirms the presence of various product phases grown across the interdiffusion zone. Time-dependent experiments indicate diffusion controlled growth of the product phase. The estimated activation energy in the temperature range 125–215°C for parabolic growth constants (and hence integrated interdiffusion coefficients) of the Ni₃Sn₄ phase shed light on the growth mechanism of the phase; whether its grain boundary controlled or lattice controlled diffusion. The location of the Kirkendall marker plane indicates that the Ni₃Sn₄ phase grows mainly by diffusion of Sn in the binary Ni–Sn system.

Keywords: diffusion, equilibrium phase, metastable phase, the Ni-Sn system

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Authors: Anu Krishna

Abstract:

Cardamom Hills geographically falls into the Western Ghat region in the state of Kerala (India). The fame of these hills dates back to antiquity as the abode of various indigenous communities and treasure house of spices like cardamom. With the colonial conquest over the region, the evergreen forests got converted into zones of mono-cropping with commercial crops such as coffee, tea, cardamom etc. on plantation basis; a process which has been further accentuated with the migration of settlers during the post-independent times. Curiously, when Cardamom Hills are better known today as the plantation belt of the country or as one of the most fostering grounds of agrarian capitalism producing the lion share of Indian cardamom, the indigenous communities of the place such as the Mannans got alienated of their ancestral lands, became inter-generational proletariats and got reduced into ‘segmented spaces’ called the settlements. While dispossession of land for plantations has dislocated the economic life of the Mannans, the migration of the settlers has resulted into a complete social, cultural, political and demographic dominion over them. This has not only relegated their existential relations, history, culture and association with the place but also condensed them as the ‘Other’ in their own territories. Therefore inquisitively, violation of rights of the communities like Mannans, encroachment of their lands, negation towards their very existence and distortion of their history gets defined as the ‘Manifest Destiny’ of the people and place whereby its inevitability gets manufactured. This paper is an attempt to elicit the ways in which the formation of Mannan settlements are interconnected to the historical reality and contemporary opulence of the plantation industry in the place. The arguments put forth by this study is based on extensive ethnographic fieldwork conducted in various Mannan settlements in the cardamom hills. The study basically dwells on to the methodological premises of multi-sited ethnography wherein information was gathered from different sites such as settlements, plantations and other interactive spaces wherein the Mannans from the settlements engages in socio-economic, cultural and political relations. Such an attempt was made to understand in depth the associations and interactions that people in the settlements have among themselves and others. The study equally uses the method of oral history to understand the alternative history, the socio-cultural and economic life of the people before the importation of plantations to the place. The paper gauges into the ways in which settlements imprisons generations of Mannans into plantation work and acts as moulds for subservient, hardworking plantation labourers.

Keywords: Cardamom Hills, plantations, labourers, Mannans, segmented spaces, settlements

Procedia PDF Downloads 243

Authors: Suveen Kumar

Abstract:

Oral cancer (OC) is the sixth most death causing cancer in world which includes tumour of lips, floor of the mouth, tongue, palate, cheeks, sinuses, throat, etc. Conventionally, the techniques used for OC detection are toluidine blue staining, biopsy, liquid-based cytology, visual attachments, etc., however these are limited by their highly invasive nature, low sensitivity, time consumption, sophisticated instrument handling, sample processing and high cost. Therefore, we developed biosensing chips for non-invasive detection of OC via CYFRA-21-1 biomarker. CYFRA-21-1 (molecular weight: 40 kDa) is secreted in saliva of OC patients which is a non-invasive biological fluid with a cut-off value of 3.8 ng mL-1, above which the subjects will be suffering from oral cancer. Therefore, in first work, 3-aminopropyl triethoxy silane (APTES) functionalized zirconia (ZrO2) nanoparticles (APTES/nZrO2) were used to successfully detect CYFRA-21-1 in a linear detection range (LDR) of 2-16 ng mL-1 with sensitivity of 2.2 µA mL ng-1. Successively, APTES/nZrO2-RGO was employed to prevent agglomeration of ZrO2 by providing high surface area reduced graphene oxide (RGO) support and much wider LDR (2-22 ng mL-1) was obtained with remarkable limit of detection (LOD) as 0.12 ng mL-1. Further, APTES/nY2O3/ITO platform was used for oral cancer bioseneor development. The developed biosensor (BSA/anti-CYFRA-21-1/APTES/nY2O3/ITO) have wider LDR (0.01-50 ng mL-1) with remarkable limit of detection (LOD) as 0.01 ng mL-1. To improve the sensitivity of the biosensing platform, nanocomposite of yattria stabilized nanostructured zirconia-reduced graphene oxide (nYZR) based biosensor has been developed. The developed biosensing chip having ability to detect CYFRA-21-1 biomolecules in the range of 0.01-50 ng mL-1, LOD of 7.2 pg mL-1 with sensitivity of 200 µA mL ng-1. Further, the applicability of the fabricated biosensing chips were also checked through real sample (saliva) analysis of OC patients and the obtained results showed good correlation with the standard protein detection enzyme linked immunosorbent assay (ELISA) technique.

Keywords: non-invasive, oral cancer, nanomaterials, biosensor, biochip

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Authors: Ane Larrea, Victor Sebastian, Manuel Arruebo, Jesus Santamaria

Abstract:

We present a gas-liquid microfluidic system as a reactor to obtain magnetite nanoparticles with an excellent degree of control regarding their crystalline phase, shape and size. Several types of microflow approaches were selected to prevent nanomaterial aggregation and to promote homogenous size distribution. The selected reactor consists of a mixer stage aided by ultrasound waves and a reaction stage using a N2-liquid segmented flow to prevent magnetite oxidation to non-magnetic phases. A milli-fluidic reactor was developed to increase the production rate where a magnetite throughput close to 450 mg/h in a continuous fashion was obtained.

Keywords: continuous production, magnetic nanoparticles, microfluidics, nanomaterials

Procedia PDF Downloads 592

Authors: Kathryn Rooney, Kaitlyn Eddy, Evan Landers, Weihui Li

Abstract:

The international mortality rate for neonates and infants has been declining at a disproportionally low rate when compared to the overall decline in child mortality in recent decades. A significant portion of infant deaths could be prevented with the implementation of low-cost and easy to use physiological monitoring devices, by enabling early identification of symptoms before they progress into life-threatening illnesses. The oral diagnostic device discussed in this paper serves to continuously monitor the key vital signs of body temperature, respiratory rate, heart rate, and oxygen saturation. The device mimics an infant pacifier, designed to be easily tolerated by infants as well as orthodontically inert. The fundamental measurements are gathered via thermistors and a pulse oximeter, each encapsulated in medical-grade silicone and wired internally to a microcontroller chip. The chip then translates the raw measurements into physiological values via an internal algorithm, before outputting the data to a liquid crystal display screen and an Android application. Additionally, a biological sample collection chamber is incorporated into the internal portion of the device. The movement within the oral chamber created by sucking on the pacifier-like device pushes saliva through a small check valve in the distal end, where it is accumulated and stored. The collection chamber can be easily removed, making the sample readily available to be tested for various diseases and analytes. With the vital sign monitoring and sample collection offered by this device, abnormal fluctuations in physiological parameters can be identified and appropriate medical care can be sought. This device enables preventative diagnosis for infants who may otherwise have gone undiagnosed, due to the inaccessibility of healthcare that plagues vast numbers of underprivileged populations.

Keywords: neonate mortality, infant mortality, low-cost diagnostics, vital signs, saliva testing, preventative care

Procedia PDF Downloads 152

Authors: A. Zahra, G. de Cesare, D. Caputo, A. Nascetti

Abstract:

PDMS (Polydimethylsiloxane) polymer is a suitable material for biological and MEMS (Microelectromechanical systems) designers, because of its biocompatibility, transparency and high resistance under plasma treatment. PDMS round channel is always been of great interest due to its ability to confine the liquid with membrane type micro valves. In this paper we are presenting a very simple way to form round shape microfluidic channel, which is based on reflow of positive photoresist AZ® 40 XT. With this method, it is possible to obtain channel of different height simply by varying the spin coating parameters of photoresist.

Keywords: lab-on-chip, PDMS, reflow, round microfluidic channel

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Authors: Fathi Kallel, Saida Khachira, Mohamed Ben Slima, Ahmed Ben Hamida

Abstract:

Speckle noise is a main characteristic of cardiac ultrasound images, it corresponding to grainy appearance that degrades the image quality. For this reason, the ultrasound images are difficult to use automatically in clinical use, then treatments are required for this type of images. Then a filtering procedure of these images is necessary to eliminate the speckle noise and to improve the quality of ultrasound images which will be then segmented to extract the necessary forms that exist. In this paper, we present the importance of the pre-treatment step for segmentation. This work is applied to cardiac ultrasound images. In a first step, a comparative study of speckle filtering method will be presented and then we use a segmentation algorithm to locate and extract cardiac structures.

Keywords: medical image processing, ultrasound images, Speckle noise, image enhancement, speckle filtering, segmentation, snakes

Procedia PDF Downloads 530

Authors: Sebastian Hiergeist

Abstract:

It is a common view that Unmanned Aerial Vehicles (UAV) tend to migrate into the civil airspace. This trend is challenging UAV manufacturer in plenty ways, as there come up a lot of new requirements and functional aspects. On the higher application levels, this might be collision detection and avoidance and similar features, whereas all these functions only act as input for the flight control components of the aircraft. The flight control computer (FCC) is the central component when it comes up to ensure a continuous safe flight and landing. As these systems are flight critical, they have to be built up redundantly to be able to provide a Fail-Operational behavior. Recent architectural approaches of FCCs used in UAV systems are often based on very simple microprocessors in combination with proprietary Application-Specific Integrated Circuit (ASIC) or Field Programmable Gate Array (FPGA) extensions implementing the whole redundancy functionality. In the future, such simple microprocessors may not be available anymore as they are more and more replaced by higher sophisticated System on Chip (SoC). As the avionic industry cannot provide enough market power to significantly influence the development of new semiconductor products, the use of solutions from foreign markets is almost inevitable. Products stemming from the industrial market developed according to IEC 61508, or automotive SoCs, according to ISO 26262, can be seen as candidates as they have been developed for similar environments. Current available SoC from the industrial or automotive sector provides quite a broad selection of interfaces like, i.e., Ethernet, SPI or FlexRay, that might come into account for the implementation of a redundancy network. In this context, possible network architectures shall be investigated which could be established by using the interfaces stated above. Of importance here is the avoidance of any single point of failures, as well as a proper segregation in distinct fault containment regions. The performed analysis is supported by the use of guidelines, published by the aviation authorities (FAA and EASA), on the reliability of data networks. The main focus clearly lies on the reachable level of safety, but also other aspects like performance and determinism play an important role and are considered in the research. Due to the further increase in design complexity of recent and future SoCs, also the risk of design errors, which might lead to common mode faults, increases. Thus in the context of this work also the aspect of dissimilarity will be considered to limit the effect of design errors. To achieve this, the work is limited to broadly available interfaces available in products from the most common silicon manufacturer. The resulting work shall support the design of future UAV FCCs by giving a guideline on building up a redundancy network between SoCs, solely using on board interfaces. Therefore the author will provide a detailed usability analysis on available interfaces provided by recent SoC solutions, suggestions on possible redundancy architectures based on these interfaces and an assessment of the most relevant characteristics of the suggested network architectures, like e.g. safety or performance.

Keywords: redundancy, System-on-Chip, UAV, flight control computer (FCC)

Procedia PDF Downloads 219

Authors: J. S. Kim

Abstract:

This paper presents a 0.13-µm Complementary Metal-Oxide Semiconductor (CMOS) vector modulator for beamforming system. The vector modulator features a 360° phase and gain range of -10 dB to 10 dB with a root mean square phase and amplitude error of only 2.2° and 0.45 dB, respectively. These features make it a suitable for wireless backhaul system in the 5 GHz industrial, scientific, and medical (ISM) bands. It draws a current of 20.4 mA from a 1.2 V supply. The total chip size is 1.87x1.34 mm².

Keywords: CMOS, vector modulator, beamforming, 802.11ac

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Authors: J. S. Kim, N. P. Hong

Abstract:

In this paper, a CMOS vector modulator designed for wireless backhaul system based on 802.11ac is presented. A poly phase filter and sign select switches yield two orthogonal signal paths. Two variable gain amplifiers with strongly reduced phase shift of only ±5 ° are used to weight these paths. It has a phase control range of 360 ° and a gain range of -10 dB to 10 dB. The current drawn from a 1.2 V supply amounts 20.4 mA. Using a 0.13 mm technology, the chip die area amounts 1.47x0.75 mm².

Keywords: CMOS, phase shifter, backhaul, 802.11ac

Procedia PDF Downloads 386