Search results for: 3D microfluidic chip

Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler

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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.

Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids

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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

Procedia PDF Downloads 216

Authors: Kadir Gök

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In this study, a vacuum system was developed for orthopedic drilling processes, and the most efficient processing parameters were determined using statistical analysis of temperature rise. A reverse engineering technique was used to obtain a 3D model of the chip vacuum system, and the obtained point cloud data was transferred to Solidworks software in STL format. An experimental design method was performed by selecting different parameters and their levels, such as RPM, feed rate, and drill bit diameter, to determine the most efficient processing parameters in temperature rise using ANOVA. Additionally, the bone chip-vacuum device was developed and performed successfully to collect the whole chips and fragments in the bone drilling experimental tests, and the chip-collecting device was found to be useful in removing overheating from the drilling zone. The effects of processing parameters on the temperature levels during the chip-vacuuming were determined, and it was found that bone chips and fractures can be used as autograft and allograft for tissue engineering. Overall, this study provides significant insights into the development of a vacuum system for orthopedic drilling processes and the use of bone chips and fractures in tissue engineering applications.

Keywords: vacuum system, orthopedic drilling, temperature rise, bone chips

Procedia PDF Downloads 49

Authors: Mark Davey

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Communications on a Network on Chip (NoC) produce timing information, i.e., network injection delays, packet traversal times, throughput metrics, and other attributes relating to the traffic being sent across the chip. The security requirements of a platform encompass each node to operate with confidentiality, integrity, and availability (ISO 27001). Inherently, a shared NoC interconnect is exposed to analysis of timing patterns created by contention for the network components, i.e., links and switches/routers. This phenomenon is defined as information leakage, which represents a ‘side channel’ of sensitive information that can be correlated to platform activity. The key algorithm presented in this paper evaluates how an adversary can control two platform neighbouring nodes of a target node to obtain sensitive information about communication with the target node. The actual information obtained is the period value of a periodic task communication. This enacts a breach of the expected confidentiality of a node operating in a multiprocessor platform. An experimental investigation of the side channel is undertaken to judge the level and significance of inferred information produced by access times to the NoC. Results are presented with a series of expanding task set scenarios to evaluate the efficacy of the side channel detection algorithm as the network load increases.

Keywords: embedded systems, multiprocessor, network on chip, side channel

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Authors: Zara L. Sheady

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Fluidic oscillators are being utilised in an increasing number of applications in a wide variety of areas; these include on-board vehicle cleaning systems, flow separation control on aircraft and in fluidic circuitry. With this increased use, there is a further understanding required for the mechanics of the fluidics of the fluidic oscillator and why they work in the manner that they do. ANSYS CFX has been utilized to visualise the pressure and velocity within a microfluidic feedback oscillator. The images demonstrate how the pressure vortices build within the oscillator at the points where the velocity is diverted from linear motion through the oscillator. With an enhanced understanding of the pressure and velocity distributions within a fluidic oscillator, it will enable users of microfluidics to more greatly tailor fluidic nozzles to their specification.

Keywords: ANSYS CFX, control, fluidic oscillators, mechanics, pressure, relationship, velocity

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Authors: Vedat Coskun, Fahri Soylemezgiller, Busra Ozdenizci, Kerem Ok

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In recent years, several smart card solutions for transportation services of cities with different technical infrastructures and business models has emerged considerably, which triggers new business and technical opportunities. In order to create a unique system, we present a novel, promising system called Multifunctional City Smart Card System to be used in all cities that provides transportation and loyalty services based on the MasterCard M/Chip Advance standards. The proposed system provides a unique solution for transportation services of large cities over the world, aiming to answer all transportation needs of citizens. In this paper, development of the Multifunctional City Smart Card System and system requirements are briefly described. Moreover, performance analysis results of M/Chip Advance Compatible Validators which is the system's most important component are presented.

Keywords: smart card, m/chip advance standard, city transportation, performance analysis

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Authors: A. Aslihan Gokaltun, Martin L. Yarmush, Ayse Asatekin, O. Berk Usta

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In the last decade microfabrication processes including rapid prototyping techniques have advanced rapidly and achieved a fairly matured stage. These advances encouraged and enabled the use of microfluidic devices by a wider range of users with applications in biological separations, and cell and organoid cultures. Accordingly, a significant current challenge in the field is controlling biomolecular interactions at interfaces and the development of novel biomaterials to satisfy the unique needs of the biomedical applications. Poly(dimethylsiloxane) (PDMS) is by far the most preferred material in the fabrication of microfluidic devices. This can be attributed its favorable properties, including: (1) simple fabrication by replica molding, (2) good mechanical properties, (3) excellent optical transparency from 240 to 1100 nm, (4) biocompatibility and non-toxicity, and (5) high gas permeability. However, high hydrophobicity (water contact angle ~108°±7°) of PDMS often limits its applications where solutions containing biological samples are concerned. In our study, we created a simple, easy method for modifying the surface chemistry of PDMS microfluidic devices through the addition of surface-segregating additives during manufacture. In this method, a surface segregating copolymer is added to precursors for silicone and the desired device is manufactured following the usual methods. When the device surface is in contact with an aqueous solution, the copolymer self-organizes to expose its hydrophilic segments to the surface, making the surface of the silicone device more hydrophilic. This can lead to several improved performance criteria including lower fouling, lower non-specific adsorption, and better wettability. Specifically, this approach is expected to be useful for the manufacture of microfluidic devices. It is also likely to be useful for manufacturing silicone tubing and other materials, biomaterial applications, and surface coatings.

Keywords: microfluidics, non-specific protein adsorption, PDMS, PEG, copolymer

Procedia PDF Downloads 233

Authors: M. K. Benhaoua, A. E. H. Benyamina, T. Djeradi, P. Boulet

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In this paper, we propose adaptive routing that considers the routing of communications in order to optimize the overall performance. The routing technique uses a newly proposed Algorithm to route communications between the tasks. The routing we propose of the communications leads to a better optimization of several performance metrics (time and energy consumption). Experimental results show that the proposed routing approach provides significant performance improvements when compared to those using static routing.

Keywords: multi-processor systems-on-chip (mpsocs), network-on-chip (noc), heterogeneous architectures, adaptive routin

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Authors: Vinayaga Jagadessh Raja, R. Ganesan, S. Ramesh Kumar

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An ever more significant fraction of the overall power dissipation of a network-on-chip (NoC) based system on- chip (SoC) is due to the interconnection scheme. In information, as equipment shrinks, the power contributes of NoC links starts to compete with that of NoC routers. In this paper, we propose the use of clock gating in the data encoding techniques as a viable way to reduce both power dissipation and time consumption of NoC links. The projected scramble scheme exploits the wormhole switching techniques. That is, flits are scramble by the network interface (NI) before they are injected in the network and are decoded by the target NI. This makes the scheme transparent to the underlying network since the encoder and decoder logic is integrated in the NI and no modification of the routers structural design is required. We review the projected scramble scheme on a set of representative data streams (both synthetic and extracted from real applications) showing that it is possible to reduce the power contribution of both the self-switching activity and the coupling switching activity in inter-routers links.

Keywords: Xilinx 12.1, power consumption, Encoder, NOC

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Authors: Ching-Feng Chen, Ching-Chih Tsai

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With the size of the transistor gradually approaching the physical limit, it challenges the persistence of Moore’s Law due to the development of the high numerical aperture (high-NA) lithography equipment and other issues such as short channel effects. In the context of the ever-increasing technical requirements of portable devices and high-performance computing, relying on the law continuation to enhance the chip density will no longer support the prospects of the electronics industry. Weighing the chip’s power consumption-performance-area-cost-cycle time to market (PPACC) is an updated benchmark to drive the evolution of the advanced wafer nanometer (nm). The advent of two and half- and three-dimensional (2.5 and 3D)- Very-Large-Scale Integration (VLSI) packaging based on Through Silicon Via (TSV) technology has updated the traditional die assembly methods and provided the solution. This overview investigates the up-to-date and cutting-edge packaging technologies for 2.5D and 3D integrated circuits (ICs) based on the updated transistor structure and technology nodes. The author concludes that multi-chip solutions for 2.5D and 3D IC packagings are feasible to prolong Moore’s Law.

Keywords: moore’s law, high numerical aperture, power consumption-performance-area-cost-cycle time to market, 2.5 and 3D- very-large-scale integration, packaging, through silicon via

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Authors: M. S. Kaiser, S. Reaz Ahmed

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Chip formation characteristics are investigated during surface finishing of high density polyethylene (HDPE) samples using a shaper machine. Both the cutting speed and depth of cut are varied continually to enable observations under various machining conditions. The generated chips are analyzed in terms of their shape, size, and deformation. Their physical appearances are also observed using digital camera and optical microscope. The investigation shows that continuous chips are obtained for all the cutting conditions. It is observed that cutting speed is more influential than depth of cut to cause dimensional changes of chips. Chips curl radius is also found to increase gradually with the increase of cutting speed. The length of continuous chips remains always smaller than the job length, and the corresponding discrepancies are found to be more prominent at lower cutting speed. Microstructures of the chips reveal that cracks are formed at higher cutting speeds and depth of cuts, which is not that significant at low depth of cut.

Keywords: HDPE, surface-finishing, chip formation, deformation, roughness

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Authors: Shashank Kumar, Mansi Chandra, Ujjawal Singh, Parth Gupta, Rishi Ram, Arnab Sarkar

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Milk is one of the basic and primary sources of food and energy as we start consuming milk from birth. Hence, milk quality and purity and checking the concentration of its constituents become necessary steps. Considering the importance of the purity of milk for human health, the following study has been carried out to simultaneously detect and quantify the different adulterants like urea and starch in milk with the help of a paper-based microfluidic device integrated with a smartphone. The detection of the concentration of urea and starch is based on the principle of colorimetry. In contrast, the fluid flow in the device is based on the capillary action of porous media. The microfluidic channel proposed in the study is equipped with a specialized detection zone, and it employs a colorimetric indicator undergoing a visible color change when the milk gets in touch or reacts with a set of reagents which confirms the presence of different adulterants in the milk. In our proposed work, we have used iodine to detect the percentage of starch in the milk, whereas, in the case of urea, we have used the p-DMAB. A direct correlation has been found between the color change intensity and the concentration of adulterants. A calibration curve was constructed to find color intensity and subsequent starch and urea concentration. The device has low-cost production and easy disposability, which make it highly suitable for widespread adoption, especially in resource-constrained settings. Moreover, a smartphone application has been developed to detect, capture, and analyze the change in color intensity due to the presence of adulterants in the milk. The low-cost nature of the smartphone-integrated paper-based sensor, coupled with its integration with smartphones, makes it an attractive solution for widespread use. They are affordable, simple to use, and do not require specialized training, making them ideal tools for regulatory bodies and concerned consumers.

Keywords: paper based microfluidic device, milk adulteration, urea detection, starch detection, smartphone application

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Authors: M. K. Benhaoua, A. K. Singh, A. E. H. Benyamina

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In this paper, we propose heuristic for dynamic communications mapping that considers the placement of communications in order to optimize the overall performance. The mapping technique uses a newly proposed Algorithm to place communications between the tasks. The placement we propose of the communications leads to a better optimization of several performance metrics (time and energy consumption). Experimental results show that the proposed mapping approach provides significant performance improvements when compared to those using static routing.

Keywords: Multi-Processor Systems-on-Chip (MPSoCs), Network-on-Chip (NoC), heterogeneous architectures, dynamic mapping heuristics

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Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis

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Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.

Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds

Procedia PDF Downloads 108

Authors: Itti Bist, Snehasis Bhakta, Di Jiang, Tia E. Keyes, Aaron Martin, Robert J. Forster, James F. Rusling

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DNA damage from metabolites of lipophilic drugs and pollutants, generated by enzymes, represents a major toxicity pathway in humans. These metabolites can react with DNA to form either 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is the oxidative product of DNA or covalent DNA adducts, both of which are genotoxic and hence considered important biomarkers to detect cancer in humans. Therefore, detecting reactions of metabolites with DNA is an effective approach for the safety assessment of new chemicals and drugs. Here we describe a novel electrochemiluminescent (ECL) sensor array which can detect DNA oxidation and chemical DNA damage in a single array, facilitating a more accurate diagnostic tool for genotoxicity screening. Layer-by-layer assembly of DNA and enzyme are assembled on the pyrolytic graphite array which is housed in a microfluidic device for sequential detection of two type of the DNA damages. Multiple enzyme reactions are run on test compounds using the array, generating toxic metabolites in situ. These metabolites react with DNA in the films to cause DNA oxidation and chemical DNA damage which are detected by ECL generating osmium compound and ruthenium polymer, respectively. The method is further validated by the formation of 8-oxodG and DNA adduct using similar films of DNA/enzyme on magnetic bead biocolloid reactors, hydrolyzing the DNA, and analyzing by liquid chromatography-mass spectrometry (LC-MS). Hence, this combined DNA/enzyme array/LC-MS approach can efficiently explore metabolic genotoxic pathways for drugs and environmental chemicals.

Keywords: biosensor, electrochemiluminescence, DNA damage, microfluidic array

Procedia PDF Downloads 335

Authors: Nizar Jawad Hadi, Sajad Abd Alabbas

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Because of their ability to encapsulate and release drugs in a controlled manner, microspheres fabricated from polymer emulsions using microfluidic devices have shown promise for drug delivery applications. In this study, the effects of velocity, density, viscosity, and surface tension, as well as channel diameter, on microsphere generation were investigated using Fluent Ansys software. The software was programmed with the physical properties of the polymer emulsion such as density, viscosity and surface tension. Simulation will then be performed to predict fluid flow and microsphere production and improve the design of drug delivery applications based on changes in these parameters. The effects of capillary and Weber numbers are also studied. The results of the study showed that the size of the microspheres can be controlled by adjusting the speed and diameter of the channel. Narrower microspheres resulted from narrower channel widths and higher flow rates, which could improve drug delivery efficiency, while smaller microspheres resulted from lower interfacial surface tension. The viscosity and density of the polymer emulsion significantly affected the size of the microspheres, ith higher viscosities and densities producing smaller microspheres. The loading and drug release properties of the microspheres created with the microfluidic technique were also predicted. The results showed that the microspheres can efficiently encapsulate drugs and release them in a controlled manner over a period of time. This is due to the high surface area to volume ratio of the microspheres, which allows for efficient drug diffusion. The ability to tune the manufacturing process using factors such as speed, density, viscosity, channel diameter, and surface tension offers a potential opportunity to design drug delivery systems with greater efficiency and fewer side effects.

Keywords: polymer emulsion, microspheres, numerical simulation, microfluidic device

Procedia PDF Downloads 36

Authors: Han-Bin Park, Taesam Kang, SunKi Hong, Jeong Hoi Gu

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The piezoelectric material is being used widely for actuators due to its large power density with simple structure. It can generate a larger force than the conventional actuators with the same size. Furthermore, the response time of piezoelectric actuators is very short, and thus, it can be used for very fast system applications with compact size. To control the piezoelectric actuator, we need analog signal conditioning circuits as well as digital microcontrollers. Conventional microcontrollers are not equipped with analog parts and thus the control system becomes bulky compared with the small size of the piezoelectric devices. To overcome these weaknesses, we are developing one-chip micro controller that can handle analog and digital signals simultaneously using mixed signal FPGA technology. We used the SmartFusion™ FPGA device that integrates ARM®Cortex-M3, analog interface and FPGA fabric in a single chip and offering full customization. It gives more flexibility than traditional fixed-function microcontrollers with the excessive cost of soft processor cores on traditional FPGAs. In this paper we introduce the design of single chip controller using mixed signal FPGA, SmartFusion™[1] device. To demonstrate its performance, we implemented a PI controller for power driving circuit and a 5th order H-infinity controller for the system with piezoelectric actuator in the FPGA fabric. We also demonstrated the regulation of a power output and the operation speed of a 5th order H-infinity controller.

Keywords: mixed signal FPGA, PI control, piezoelectric actuator, SmartFusion™

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Authors: Md. Anayet U. Patwari, Mohammad Ahsan Habib, Md. Tanzib Ehsan, Md Golam Ahnaf, Md. S. I. Chowdhury

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Surface roughness is one of the key quality parameters of the finished product. During any machining operation, high temperatures are generated at the tool-chip interface impairing surface quality and dimensional accuracy of products. Cutting fluids are generally applied during machining to reduce temperature at the tool-chip interface. However, usages of cutting fluids give rise to problems such as waste disposal, pollution, high cost, and human health hazard. Researchers, now-a-days, are opting towards dry machining and other cooling techniques to minimize use of coolants during machining while keeping surface roughness of products within desirable limits. In this paper, a concept of using peltier cooling effects during aluminium milling operation has been presented and adopted with an aim to improve surface roughness of the machined surface. Experimental evidence shows that peltier cooling effect provides better surface roughness of the machined surface compared to dry machining.

Keywords: aluminium, milling operation, peltier cooling effect, surface roughness

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Authors: Seul Ki Min, Gwang Heum Yoon, Jung Hyun Joo, Hwa Sung Shin

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Cellular membrane distortion is known as a factor to change intracellular signaling. However, progress of relevant studies is difficult because there are no facilities that can control membrane distortion finely. In this study, we developed microfluidic device which can inflict mechanical stress on cell membrane of Chlamydomonas reinhardtii using regular height of the channels. And cellular physiological changes were analyzed from cells cultured in the device. Excessive calcium ion influx through into cytoplasm was induced from mechanical stress. The results revealed that compressed cells had up-regulated Mat3 mRNA which regulates cell size and cell cycle from a prolonged G1 phase. Additionally, TAG used for the production of biodiesel was raised rapidly from 4 h after compression. Taken together, membrane distortion can be considered as an attractive inducer for biofuel production.

Keywords: mechanical stress, membrane distortion, Chlamydomonas reinhardtii, deflagellation, cell cycle, lipid metabolism

Procedia PDF Downloads 339

Authors: Renata Gerhardt, Detlev Belder

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Raman spectroscopy has attracted much attention as a structurally descriptive and label-free detection method. It is particularly suited for chemical analysis given as it is non-destructive and molecules can be identified via the fingerprint region of the spectra. In this work possibilities are investigated how to integrate Raman spectroscopy as a detection method for chip-based chromatography, making use of a droplet interface. A demanding task in lab-on-a-chip applications is the specific and sensitive detection of low concentrated analytes in small volumes. Fluorescence detection is frequently utilized but restricted to fluorescent molecules. Furthermore, no structural information is provided. Another often applied technique is mass spectrometry which enables the identification of molecules based on their mass to charge ratio. Additionally, the obtained fragmentation pattern gives insight into the chemical structure. However, it is only applicable as an end-of-the-line detection because analytes are destroyed during measurements. In contrast to mass spectrometry, Raman spectroscopy can be applied on-chip and substances can be processed further downstream after detection. A major drawback of Raman spectroscopy is the inherent weakness of the Raman signal, which is due to the small cross-sections associated with the scattering process. Enhancement techniques, such as surface enhanced Raman spectroscopy (SERS), are employed to overcome the poor sensitivity even allowing detection on a single molecule level. In SERS measurements, Raman signal intensity is improved by several orders of magnitude if the analyte is in close proximity to nanostructured metal surfaces or nanoparticles. The main gain of lab-on-a-chip technology is the building block-like ability to seamlessly integrate different functionalities, such as synthesis, separation, derivatization and detection on a single device. We intend to utilize this powerful toolbox to realize Raman detection in chip-based chromatography. By interfacing on-chip separations with a droplet generator, the separated analytes are encapsulated into numerous discrete containers. These droplets can then be injected with a silver nanoparticle solution and investigated via Raman spectroscopy. Droplet microfluidics is a sub-discipline of microfluidics which instead of a continuous flow operates with the segmented flow. Segmented flow is created by merging two immiscible phases (usually an aqueous phase and oil) thus forming small discrete volumes of one phase in the carrier phase. The study surveys different chip designs to realize coupling of chip-based chromatography with droplet microfluidics. With regards to maintaining a sufficient flow rate for chromatographic separation and ensuring stable eluent flow over the column different flow rates of eluent and oil phase are tested. Furthermore, the detection of analytes in droplets with surface enhanced Raman spectroscopy is examined. The compartmentalization of separated compounds preserves the analytical resolution since the continuous phase restricts dispersion between the droplets. The droplets are ideal vessels for the insertion of silver colloids thus making use of the surface enhancement effect and improving the sensitivity of the detection. The long-term goal of this work is the first realization of coupling chip based chromatography with droplets microfluidics to employ surface enhanced Raman spectroscopy as means of detection.

Keywords: chip-based separation, chip LC, droplets, Raman spectroscopy, SERS

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Authors: A. Zuchowska, A. Buta, M. Mazurkiewicz-Pawlicka, A. Malolepszy, L. Stobinski, Z. Brzozka

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In recent years, graphene-based materials are finding more and more applications in biological science. As a thin, tough, transparent and chemically resistant materials, they appear to be a very good material for the production of implants and biosensors. Interest in graphene derivatives also resulted at the beginning of research about the possibility of their application in cancer therapy. Currently, the analysis of their potential use in photothermal therapy and as a drug carrier is mostly performed. Moreover, the direct anticancer properties of graphene-based materials are also tested. Nowadays, cytotoxic studies are conducted on in vitro cell culture in standard culture vessels (macroscale). However, in this type of cell culture, the cells grow on the synthetic surface in static conditions. For this reason, cell culture in macroscale does not reflect in vivo environment. The microfluidic systems, called Lab-on-a-chip, are proposed as a solution for improvement of cytotoxicity analysis of new compounds. Here, we present the evaluation of cytotoxic properties of graphene oxide (GO) on breast, liver and colon cancer cell line in a microfluidic system in two spatial models (2D and 3D). Before cell introduction, the microchambers surface was modified by the fibronectin (2D, monolayer) and poly(vinyl alcohol) (3D, spheroids) covering. After spheroid creation (3D) and cell attachment (2D, monolayer) the selected concentration of GO was introduced into microsystems. Then monolayer and spheroids viability/proliferation using alamarBlue® assay and standard microplate reader was checked for three days. Moreover, in every day of the culture, the morphological changes of cells were determined using microscopic analysis. Additionally, on the last day of the culture differential staining using Calcein AM and Propidium iodide were performed. We were able to note that the GO has an influence on all tested cell line viability in both monolayer and spheroid arrangement. We showed that GO caused higher viability/proliferation decrease for spheroids than a monolayer (this was observed for all tested cell lines). Higher cytotoxicity of GO on spheroid culture can be caused by different geometry of the microchambers for 2D and 3D cell cultures. Probably, GO was removed from the flat microchambers for 2D culture. Those results were also confirmed by differential staining. Comparing our results with the studies conducted in the macroscale, we also proved that the cytotoxic properties of GO are changed depending on the cell culture conditions (static/ flow).

Keywords: cytotoxicity, graphene oxide, monolayer, spheroid

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Authors: Pedro Acevedo, Carlos Díaz, Mónica Vázquez, Joel Durán

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This paper describes the design of a pulse generator based on the Programmable System-on-Chip (PSoC) module. In this module, using programmable logic is possible to implement different pulses which are required for ultrasonic applications, either in a single channel or multiple channels. This module can operate with programmable frequencies from 3-74 MHz; its programming may be versatile covering a wide range of ultrasonic applications. It is ideal for low-power ultrasonic applications where PZT or PVDF transducers are used.

Keywords: PSoC, pulse generator, PVDF, ultrasonic transducer

Procedia PDF Downloads 254

Authors: Patricia B. Cruz, Catrina Jean G. Valenzuela, Analyn N. Yumang

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Nearly a hundred per million of the Filipino population is diagnosed with Chronic Kidney Disease (CKD). The early stage of CKD has no symptoms and can only be discovered once the patient undergoes urinalysis. Over the years, different methods were discovered and used for the quantification of the urinary albumin such as the immunochemical assays where most of these methods require large machinery that has a high cost in maintenance and resources, and a dipstick test which is yet to be proven and is still debated as a reliable method in detecting early stages of microalbuminuria. This research study involves the use of the liquid chromatography concept in microfluidic instruments with biosensor as a means of separation and detection respectively, and linear regression to quantify human urinary albumin. The researchers’ main objective was to create a miniature system that quantifies and detect patients’ urinary albumin while reducing the amount of volume used per five test samples. For this study, 30 urine samples of unknown albumin concentrations were tested using VITROS Analyzer and the microfluidic system for comparison. Based on the data shared by both methods, the actual vs. predicted regression were able to create a positive linear relationship with an R² of 0.9995 and a linear equation of y = 1.09x + 0.07, indicating that the predicted values and actual values are approximately equal. Furthermore, the microfluidic instrument uses 75% less in total volume – sample and reagents combined, compared to the VITROS Analyzer per five test samples.

Keywords: Chronic Kidney Disease, Linear Regression, Microfluidics, Urinary Albumin

Procedia PDF Downloads 109

Authors: Camille Perréard, Yoann Ladner, Fanny D'Orlyé, Stéphanie Descroix, Vélan Taniga, Anne Varenne, Cédric Guyon, Michael. Tatoulian, Frédéric Kanoufi, Cyrine Slim, Sophie Griveau, Fethi Bedioui

Abstract:

The development of micro total analysis systems is of major interest for contaminant and biomarker analysis. As a lab-on-chip integrates all steps of an analysis procedure in a single device, analysis can be performed in an automated format with reduced time and cost, while maintaining performances comparable to those of conventional chromatographic systems. Moreover, these miniaturized systems are either compatible with field work or glovebox manipulations. This work is aimed at developing an analytical microsystem for trace and ultra trace quantitation in complex matrices. The strategy consists in the integration of a sample pretreatment step within the lab-on-chip by a confinement zone where selective ligands are immobilized for target extraction and preconcentration. Aptamers were chosen as selective ligands, because of their high affinity for all types of targets (from small ions to viruses and cells) and their ease of synthesis and functionalization. This integrated target extraction and concentration step will be followed in the microdevice by an electrokinetic separation step and an on-line detection. Polymers consisting of cyclic olefin copolymer (COC) or fluoropolymer (Dyneon THV) were selected as they are easy to mold, transparent in UV-visible and have high resistance towards solvents and extreme pH conditions. However, because of their low chemical reactivity, surface treatments are necessary. For the design of this miniaturized diagnostics, we aimed at modifying the microfluidic system at two scales : (1) on the entire surface of the microsystem to control the surface hydrophobicity (so as to avoid any sample wall adsorption) and the fluid flows during electrokinetic separation, or (2) locally so as to immobilize selective ligands (aptamers) on restricted areas for target extraction and preconcentration. We developed different novel strategies for the surface functionalization of COC and Dyneon, based on plasma, chemical and /or electrochemical approaches. In a first approach, a plasma-induced immobilization of brominated derivatives was performed on the entire surface. Further substitution of the bromine by an azide functional group led to covalent immobilization of ligands through “click” chemistry reaction between azides and terminal alkynes. COC and Dyneon materials were characterized at each step of the surface functionalization procedure by various complementary techniques to evaluate the quality and homogeneity of the functionalization (contact angle, XPS, ATR). With the objective of local (micrometric scale) aptamer immobilization, we developed an original electrochemical strategy on engraved Dyneon THV microchannel. Through local electrochemical carbonization followed by adsorption of azide-bearing diazonium moieties and covalent linkage of alkyne-bearing aptamers through click chemistry reaction, typical dimensions of immobilization zones reached the 50 µm range. Other functionalization strategies, such as sol-gel encapsulation of aptamers, are currently investigated and may also be suitable for the development of the analytical microdevice. The development of these functionalization strategies is the first crucial step in the design of the entire microdevice. These strategies allow the grafting of a large number of molecules for the development of new analytical tools in various domains like environment or healthcare.

Keywords: alkyne-azide click chemistry (CuAAC), electrochemical modification, microsystem, plasma bromination, surface functionalization, thermoplastic polymers

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Authors: Nawang Chhunid, Gagnesh Kumar

Abstract:

On-chip memories consume a significant portion of the overall die space and power in modern microprocessors. On-chip caches depend on Static Random-Access Memory (SRAM) cells and scaling of technology occurring as per Moore’s law. Unfortunately, the scaling is affecting stability, performance, and leakage power which will become major problems for future SRAMs in aggressive nanoscale technologies due to increasing device mismatch and variations. 3T1D Dynamic Random-Access Memory (DRAM) cell is a non-destructive read DRAM cell with three transistors and a gated diode. In 3T1D DRAM cell gated diode (D1) acts as a storage device and also as an amplifier, which leads to fast read access. Due to its high tolerance to process variation, high density, and low cost of memory as compared to 6T SRAM cell, it is universally used by the advanced microprocessor for on chip data and program memory. In the present paper, it has been shown that 3T1D DRAM cell can perform better in terms of fast read access as compared to 6T, 4T, 3T SRAM cells, respectively.

Keywords: DRAM Cell, Read Access Time, Retention Time, Average Power dissipation

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Authors: R. Vasireddi, J. Kruse, M. Vakili, M. Trebbin

Abstract:

Here we present a gas dynamic virtual nozzle (GDVN) based microfluidic jetting devices for spinning of nano/microfibers. The device is fabricated by soft lithography techniques and is based on the principle of a GDVN for precise three-dimensional gas focusing of the spinning solution. The nozzle device is used to produce micro/nanofibers of a perfluorinated terpolymer (THV), which were collected on an aluminum substrate for scanning electron microscopy (SEM) analysis. The influences of air pressure, polymer concentration, flow rate and nozzle geometry on the fiber properties were investigated. It was revealed that surface properties are controlled by air pressure and polymer concentration while the diameter and shape of the fibers are influenced mostly by the concentration of the polymer solution and pressure. Alterations of the nozzle geometry had a negligible effect on the fiber properties, however, the jetting stability was affected. Round and flat fibers with differing surface properties from craters, grooves to smooth surfaces could be fabricated by controlling the above-mentioned parameters. Furthermore, the formation of surface roughness was attributed to the fast evaporation rate and velocity (mis)match between the polymer solution jet and the surrounding air stream. The diameter of the fibers could be tuned from ~250 nm to ~15 µm. Because of the simplicity of the setup, the precise control of the fiber properties, access to biocompatible nanofiber fabrication and the easy scale-up of parallel channels for high throughput, this method offers significant benefits compared to existing solution-based fiber production methods.

Keywords: gas dynamic virtual nozzle (GDVN) principle, microfluidic device, spinning, uniform nanofibers

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Authors: P. G. Kaviya, B. Muthupandian, R. Ganesan

Abstract:

On-chip routers typically have buffers are used input or output ports for temporarily storing packets. The buffers are consuming some router area and power. The multiple queues in parallel as in VC router. While running a traffic trace, not all input ports have incoming packets needed to be transferred. Therefore large numbers of queues are empty and others are busy in the network. So the time consumption should be high for the high traffic. Therefore using a RoShaQ, minimize the buffer area and time The RoShaQ architecture was send the input packets are travel through the shared queues at low traffic. At high load traffic the input packets are bypasses the shared queues. So the power and area consumption was reduced. A parallel cross bar architecture is proposed in this project in order to reduce the power consumption. Also a new adaptive weighted routing algorithm for 8-port router architecture is proposed in order to decrease the delay of the network on chip router. The proposed system is simulated using Modelsim and synthesized using Xilinx Project Navigator.

Keywords: buffer, RoShaQ architecture, shared queue, VC router, weighted routing algorithm

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Authors: Mahdiar Hosseinghadiry, Razali Ismail, F. Fotovati

Abstract:

One of the most important and challenging tasks in testing network-on-chip based system-on-chips (NoC based SoCs) is to verify the communication entity. It is important because of its usage for transferring both data packets and test patterns for intellectual properties (IPs) during normal and test mode. Hence, ensuring of NoC reliability is required for reliable IPs functionality and testing. On the other hand, it is challenging due to the required time to test it and the way of transferring test patterns from the tester to the NoC components. In this paper, two testing techniques for mesh-based NoC interconnections are proposed. The first one is based on one-by-one testing and the second one divides NoC interconnects into three parts, horizontal links of switches in even columns, horizontal links of switches in odd columns and all vertical. A design for testability (DFT) architecture is represented to send test patterns directly to each switch under test and also support the proposed testing techniques by providing a loopback path in each switch. The simulation results shows the second proposed testing mechanism outperforms in terms of test time because this method test all the interconnects in only three phases, independent to the number of existed interconnects in the network, while test time of other methods are highly dependent to the number of switches and interconnects in the NoC.

Keywords: on chip, interconnection testing, horizontal-vertical testing, enhanced unicast

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Authors: M. Agostini, A. Sonato, G. Greco, M. Travagliati, G. Ruffato, E. Gazzola, D. Liuni, F. Romanato, M. Cecchini

Abstract:

Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry.

Keywords: biosensor, microfluidics, surface acoustic wave, surface plasmon resonance

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Authors: Ibrahim Aly, Manal Ahmed, Mahmoud M. El-Shall

Abstract:

Filariasis is a parasitic disease caused by small roundworms. The filarial worms are transmitted and spread by blood-feeding black flies and mosquitoes. Lymphatic filariasis (Elephantiasis) is caused by Wuchereriabancrofti, Brugiamalayi, and Brugiatimori. Elimination of Lymphatic filariasis necessitates an increasing demand for valid, reliable, and rapid diagnostic kits. Nanodiagnostics involve the use of nanotechnology in clinical diagnosis to meet the demands for increased sensitivity, specificity, and early detection in less time. The aim of this study was to evaluate the nano-based enzymelinked immunosorbent assay (ELISA) and novel nano-chip card as a rapid test for detection of filarial antigen in serum samples of human filariasis in comparison with traditional -ELISA. Serum samples were collected from an infected human with filarial gathered across Egypt's governorates. After receiving informed consenta total of 45 blood samples of infected individuals residing in different villages in Gharbea governorate, which isa nonendemic region for bancroftianfilariasis, healthy persons living in nonendemic locations (20 persons), as well as sera from 20 other parasites, affected patients were collected. The microfilaria was checked in thick smears of 20 µl night blood samples collected during 20-22 hrs. All of these individuals underwent the following procedures: history taking, clinical examination, and laboratory investigations, which included examination of blood samples for microfilaria using thick blood film and serological tests for detection of the circulating filarial antigen using polyclonal antibody- ELISA, nano-based ELISA, and nano-chip card. In the present study, a recently reported polyoclonal antibody specific to tegumental filarial antigen was used in developing nano-chip card and nano-ELISA compared to traditional ELISA for the detection of circulating filarial antigen in sera of patients with bancroftianfilariasis. The performance of the ELISA was evaluated using 45 serum samples. The ELISA was positive with sera from microfilaremicbancroftianfilariasis patients (n = 36) with a sensitivity of 80 %. Circulating filarial antigen was detected in 39/45 patients who were positive for circulating filarial antigen using nano-ELISA with a sensitivity of 86.6 %. On the other hand, 42 out of 45 patients were positive for circulating filarial antigen using nano-chip card with a sensitivity of 93.3%.In conclusion, using a novel nano-chip assay could potentially be a promising alternative antigen detection test for bancroftianfilariasis.

Keywords: lymphatic filariasis, nanotechnology, rapid diagnosis, elisa technique

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