30 results on '"Lidija Malic"'
Search Results
2. Automated sample-to-answer centrifugal microfluidic system for rapid molecular diagnostics of SARS-CoV-2
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Lidija Malic, Daniel Brassard, Dillon Da Fonte, Christina Nassif, Maxence Mounier, André Ponton, Matthias Geissler, Matthew Shiu, Keith J. Morton, and Teodor Veres
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Clinical Laboratory Techniques ,SARS-CoV-2 ,Microfluidics ,Biomedical Engineering ,COVID-19 ,Bioengineering ,General Chemistry ,Sensitivity and Specificity ,Biochemistry ,COVID-19 Testing ,Molecular Diagnostic Techniques ,Humans ,RNA, Viral ,Pathology, Molecular ,Nucleic Acid Amplification Techniques - Abstract
Testing for SARS-CoV-2 is one of the most important assets in COVID-19 management and mitigation. At the onset of the pandemic, SARS-CoV-2 testing was uniquely performed in central laboratories using RT-qPCR. RT-qPCR relies on trained personnel operating complex instrumentation, while time-to-result can be lengthy (
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- 2022
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3. Multifunctional magnetic nanoparticle cloud assemblies for in situ capture of bacteria and isolation of microbial DNA
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Lidija Malic, Matthias Geissler, Lucas Poncelet, Christina Nassif, Teodor Veres, Gaetan Veilleux, Liviu Clime, Keith Morton, and Dillon Da Fonte
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In situ ,Analyte ,Lysis ,Microbial DNA ,Chemistry ,Nanoparticle ,medicine.disease_cause ,Biochemistry ,DNA extraction ,Analytical Chemistry ,Matrix (chemical analysis) ,Electrochemistry ,medicine ,Biophysics ,Environmental Chemistry ,sense organs ,Escherichia coli ,Spectroscopy - Abstract
We investigate the formation of suspended magnetic nanoparticle (MNP) assemblies (M-clouds) and their use for in situ bacterial capture and DNA extraction. M-clouds are obtained as a result of magnetic field density variations when magnetizing an array of micropillars coated with a soft ferromagnetic NiP layer. Numerical simulations suggest that the gradient in the magnetic field created by the pillars is four orders of magnitude higher than the gradient generated by the external magnets. The pillars therefore serve as the sole magnetic capture sites for MNPs which accumulate on opposite sides of each pillar facing the magnets. Composed of loosely aggregated MNPs, the M-cloud can serve as a porous capture matrix for target analyte flowing through the array. The concept is demonstrated by using a multifunctional M-cloud comprising immunomagnetic NPs (iMNPs) for capture of Escherichia coli O157:H7 from river water along with silica-coated NPs for subsequent isolation and purification of microbial DNA released upon bacterial lysis. Confocal microscopy imaging of fluorescently labeled iMNPs and E. coli O157:H7 reveals that bacteria are trapped in the M-cloud region between micropillars. Quantitative assessment of in situ bacterial capture, lysis and DNA isolation using real-time polymerase chain reaction shows linear correlation between DNA output and input bacteria concentration, making it possible to confirm E. coli 0157:H7 at 103 cells per mL. The M-cloud method further provides one order of magnitude higher DNA output concentrations than incubation of the sample with iMNPs in a tube for an equivalent period of time (e.g., 10 min). Results from assays performed in the presence of Listeria monocytogenes (at 106 cells per mL each) suggest that non-target organisms do not affect on-chip E. coli capture, DNA extraction efficiency and quality of the eluted sample.
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- 2021
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4. Real-time monitoring of bead-based DNA hybridization in a microfluidic system: study of amplicon hybridization behavior on solid supports
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Sébastien Chapdelaine, David Béliveau-Viel, Lidija Malic, Eric A. Martel, Denis Boudreau, Teodor Veres, Michel G. Bergeron, Matthias Geissler, Jean-François Gravel, Maurice Boissinot, Régis Peytavi, and Karel Boissinot
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Microfluidics ,02 engineering and technology ,Bead ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Complementary DNA ,Monolayer ,Electrochemistry ,Environmental Chemistry ,Spectroscopy ,Oligonucleotide ,DNA–DNA hybridization ,Nucleic Acid Hybridization ,DNA ,Amplicon ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,chemistry ,visual_art ,visual_art.visual_art_medium ,Biophysics ,DNA Probes ,Oligonucleotide Probes ,0210 nano-technology - Abstract
DNA hybridization phenomena occurring on solid supports are not understood as clearly as aqueous phase hybridizations and mathematical models cannot predict some empirically obtained results. Ongoing research has identified important parameters but remains incomplete to accurately account for all interactions. It has previously been shown that the length of the overhanging (dangling) end of the target DNA strand following hybridization to the capture probe is correlated to interactions with the complementary strand in solution which can result in unbinding of the target and its release from the surface. We have developed an instrument for real-time monitoring of DNA hybridization on spherical particles functionalized with oligonucleotide capture probes and arranged in the form of a tightly packed monolayer bead bed inside a microfluidic cartridge. The instrument is equipped with a pneumatic module to mediate displacement of fluid on the cartridge. We compared this system to both conventional (passive) and centrifugally-driven (active) microfluidic microarray hybridization on glass slides to establish performance levels for the detection of single nucleotide polymorphisms. The system was also used to study the effect of the dangling end's length in real-time when the immobilized target DNA is exposed to the complementary strand in solution. Our findings indicate that increasing the length of the dangling end leads to desorption of target amplicons from bead-bound capture probes at a rate approaching that of the initial hybridization process. Finally, bead bed hybridization was performed with Streptococcus agalactiae cfb gene amplicons obtained from randomized clinical samples, which allowed for identification of group B streptococci within 5–15 min. The methodology presented here is useful for investigating competitive hybridization mechanisms on solid supports and to rapidly validate the suitability of microarray capture probes.
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- 2021
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5. Evaporation-Driven Water-in-Water Droplet Formation
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Abdelrahman Elmanzalawy, Scott S. H. Tsai, Teodor Veres, Morteza Jeyhani, Keith Morton, Lidija Malic, and Byeong-Ui Moon
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liquids ,Aqueous solution ,Materials science ,Contact line ,technology, industry, and agriculture ,Evaporation ,Surfaces and Interfaces ,Substrate (electronics) ,Condensed Matter Physics ,amorphous materials ,eye diseases ,evaporation ,Chemical engineering ,visual_art ,Emulsion ,Electrochemistry ,visual_art.visual_art_medium ,encapsulation ,Magnetic nanoparticles ,General Materials Science ,Thermoplastic elastomer ,Polycarbonate ,substrates ,Spectroscopy - Abstract
We present new observations of aqueous two-phase system (ATPS) thermodynamic and interfacial phenomena that occur inside sessile droplets due to water evaporation. Sessile droplets that contain polymeric solutions, which are initially in equilibrium in a single phase, are observed at their three-phase liquid-solid-air contact line. As evaporation of a sessile droplet proceeds, we find that submicron secondary water-in-water (W/W) droplets emerge spontaneously at the edges of the mother sessile droplet due to the resulting phase separation from water evaporation. To understand this phenomenon, we first study the secondary W/W droplet formation process on different substrate materials, namely, glass, polycarbonate (PC), thermoplastic elastomer (TPE), poly(dimethylsiloxane)-coated glass slide (PDMS substrate), and Teflon-coated glass slide (Teflon substrate), and show that secondary W/W droplet formation arises only in lower-contact-angle substrates near the three-phase contact line. Next, we characterize the size of the emergent secondary W/W droplets as a function of time. We observe that W/W drops are formed, coalesced, aligned, and trapped along the contact line of the mother droplet. We demonstrate that this W/W multiple emulsion system can be used to encapsulate magnetic particles and blood cells, and achieve size-based separation. Finally, we show the applicability of this system for protein sensing. This is the first experimental observation of evaporation-induced secondary W/W droplet generation in a sessile droplet. We anticipate that the phenomena described here may be applicable to some biological assay applications, for example, biomarker detection, protein sensing, and point-of-care diagnostic testing.
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- 2020
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6. Multifunctional magnetic nanoparticle cloud assemblies for
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Lucas, Poncelet, Lidija, Malic, Liviu, Clime, Matthias, Geissler, Keith J, Morton, Christina, Nassif, Dillon, Da Fonte, Gaétan, Veilleux, and Teodor, Veres
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Immunomagnetic Separation ,DNA ,Escherichia coli O157 ,Magnetite Nanoparticles ,Listeria monocytogenes - Abstract
We investigate the formation of suspended magnetic nanoparticle (MNP) assemblies (M-clouds) and their use for
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- 2021
7. Centrifugal microfluidic lab-on-a-chip system with automated sample lysis, DNA amplification and microarray hybridization for identification of enterohemorrhagic
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Matthias, Geissler, Daniel, Brassard, Liviu, Clime, Ana Victoria C, Pilar, Lidija, Malic, Jamal, Daoud, Virginie, Barrère, Christian, Luebbert, Burton W, Blais, Nathalie, Corneau, and Teodor, Veres
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DNA, Bacterial ,Enterohemorrhagic Escherichia coli ,Lab-On-A-Chip Devices ,Nucleic Acid Hybridization ,Oligonucleotide Array Sequence Analysis - Abstract
The development of technology for the rapid, automated identification of bacterial culture isolates can help regulatory agencies to shorten response times in food safety surveillance, compliance, and enforcement as well as outbreak investigations. While molecular methods such as polymerase chain reaction (PCR) enable the identification of microbial organisms with high sensitivity and specificity, they generally rely on sophisticated instrumentation and elaborate workflows for sample preparation with an undesirably high level of hands-on engagement. Herein, we describe the design, operation and performance of a lab-on-a-chip system integrating thermal lysis, PCR amplification and microarray hybridization on the same cartridge. The assay is performed on a centrifugal microfluidic platform that allows for pneumatic actuation of liquids during rotation, making it possible to perform all fluidic operations in a fully-automated fashion without the need for integrating active control elements on the microfluidic cartridge. The cartridge, which is fabricated from hard and soft thermoplastic polymers, is compatible with high-volume manufacturing (e.g., injection molding). Chip design and thermal interface were both optimized to ensure efficient heat transfer and allow for fast thermal cycling during the PCR process. The integrated workflow comprises 14 steps and takes less than 2 h to complete. The only manual steps are related to loading of the sample and reagents on the cartridge as well as fluorescence imaging of the microarray. On-chip lysis and PCR amplification both provided results comparable to those obtained by bench-top instrumentation. The microarray, incorporating a panel of oligonucleotide probes for multiplexed detection of seven enterohemorrhagic E. coli priority serotypes, was implemented on a cyclic olefin copolymer substrate using a novel activation scheme that involves the conversion of hydroxyl groups (derived from oxygen plasma treatment) into reactive cyanate ester using cyanogen bromide. On-chip hybridization was demonstrated in a non-quantitative fashion using fluorescently-labelled gene markers for E. coli O157:H7 (rfbO157, eae, vt1, and vt2) obtained through a multiplexed PCR amplification step.
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- 2020
8. Centrifugal microfluidic lab-on-a-chip system with automated sample lysis, DNA amplification and microarray hybridization for identification of enterohemorrhagic Escherichia coli culture isolates
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Ana Victoria C. Pilar, Jamal Daoud, Lidija Malic, D. Brassard, Virginie Barrère, Nathalie Corneau, Teodor Veres, Christian C. Luebbert, Matthias Geissler, Liviu Clime, and Burton W. Blais
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Lysis ,Chromatography ,Oligonucleotide ,010401 analytical chemistry ,Microfluidics ,02 engineering and technology ,Lab-on-a-chip ,Cyclic olefin copolymer ,021001 nanoscience & nanotechnology ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Analytical Chemistry ,law.invention ,Cartridge ,chemistry.chemical_compound ,chemistry ,law ,Electrochemistry ,Environmental Chemistry ,Sample preparation ,Fluidics ,0210 nano-technology ,Spectroscopy - Abstract
The development of technology for the rapid, automated identification of bacterial culture isolates can help regulatory agencies to shorten response times in food safety surveillance, compliance, and enforcement as well as outbreak investigations. While molecular methods such as polymerase chain reaction (PCR) enable the identification of microbial organisms with high sensitivity and specificity, they generally rely on sophisticated instrumentation and elaborate workflows for sample preparation with an undesirably high level of hands-on engagement. Herein, we describe the design, operation and performance of a lab-on-a-chip system integrating thermal lysis, PCR amplification and microarray hybridization on the same cartridge. The assay is performed on a centrifugal microfluidic platform that allows for pneumatic actuation of liquids during rotation, making it possible to perform all fluidic operations in a fully-automated fashion without the need for integrating active control elements on the microfluidic cartridge. The cartridge, which is fabricated from hard and soft thermoplastic polymers, is compatible with high-volume manufacturing (e.g., injection molding). Chip design and thermal interface were both optimized to ensure efficient heat transfer and allow for fast thermal cycling during the PCR process. The integrated workflow comprises 14 steps and takes less than 2 h to complete. The only manual steps are related to loading of the sample and reagents on the cartridge as well as fluorescence imaging of the microarray. On-chip lysis and PCR amplification both provided results comparable to those obtained by bench-top instrumentation. The microarray, incorporating a panel of oligonucleotide probes for multiplexed detection of seven enterohemorrhagic E. coli priority serotypes, was implemented on a cyclic olefin copolymer substrate using a novel activation scheme that involves the conversion of hydroxyl groups (derived from oxygen plasma treatment) into reactive cyanate ester using cyanogen bromide. On-chip hybridization was demonstrated in a non-quantitative fashion using fluorescently-labelled gene markers for E. coli O157:H7 (rfbO157, eae, vt1, and vt2) obtained through a multiplexed PCR amplification step.
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- 2020
9. In-situ gold nanoparticle synthesis in polymer films
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Xuefeng Zhang, Matthias Geissler, Jamal Daoud, Lidija Malic, Keith Morton, and Teodor Veres
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Materials science ,Fabrication ,010504 meteorology & atmospheric sciences ,optical films ,Radical polymerization ,Nanoparticle ,02 engineering and technology ,01 natural sciences ,Metal ,parasitic diseases ,Acrylic resin ,substrates ,Plasmon ,polymers ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,technology, industry, and agriculture ,Polymer ,gold ,021001 nanoscience & nanotechnology ,chemistry ,Chemical engineering ,visual_art ,visual_art.visual_art_medium ,0210 nano-technology ,Photoinitiator ,optical device fabrication - Abstract
A versatile method for fabricating both plasmonic and conductive metal structures in situ in polymer materials is presented. The process relies on UV induced radical polymerization of acrylic resin and gold nanoparticle formation by the reduction of a gold precursor in the presence of a photoinitiator. The room temperature fabrication process provides control over nanoparticle size, growth and distribution within the polymer matrix., 2020 IEEE 20th International Conference on Nanotechnology (IEEE-NANO), July 29-31, 2020, Montreal, QC, Canada
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- 2020
10. Methylation specific multiplex droplet PCR using polymer droplet generator device for hematological diagnostics
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Ljuboje Lukic, Mojra Janta, Christina Nassif, Alex Boutin, Abdelrahman Elmanzalawy, Dillon Da Fonte, Teodor Veres, Matthias Geissler, Jamal Daoud, and Lidija Malic
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Hematologic Tests ,General Immunology and Microbiology ,Polymers ,General Chemical Engineering ,General Neuroscience ,Microfluidics ,Computational biology ,Methylation ,DNA Methylation ,Peripheral blood mononuclear cell ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,chemistry ,CpG site ,DNA methylation ,Leukocytes, Mononuclear ,Humans ,Multiplex ,Epigenetics ,Multiplex Polymerase Chain Reaction ,DNA - Abstract
A multiplexed droplet PCR (mdPCR) workflow and detailed protocol for determining epigenetic-based white blood cell (WBC) differential count is described, along with a thermoplastic elastomer (TPE) microfluidic droplet generation device. Epigenetic markers are used for WBC subtyping which is of important prognostic value in different diseases. This is achieved through the quantification of DNA methylation patterns of specific CG-rich regions in the genome (CpG loci). In this paper, bisulfite-treated DNA from peripheral blood mononuclear cells (PBMCs) is encapsulated in droplets with mdPCR reagents including primers and hydrolysis fluorescent probes specific for CpG loci that correlate with WBC sub-populations. The multiplex approach allows for the interrogation of many CpG loci without the need for separate mdPCR reactions, enabling more accurate parametric determination of WBC sub-populations using epigenetic analysis of methylation sites. This precise quantification can be extended to different applications and highlights the benefits for clinical diagnosis and subsequent prognosis.
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- 2020
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11. Buoyancy-driven step emulsification on pneumatic centrifugal microfluidic platforms
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Liviu Clime, Matthias Geissler, Luke Lukic, Lidija Malic, Teodor Veres, and Jamal Daoud
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Centrifugal force ,Materials science ,Buoyancy ,Microfluidics ,Biomedical Engineering ,Bioengineering ,General Chemistry ,Mechanics ,Numerical models ,engineering.material ,Biochemistry ,Volumetric flow rate ,engineering ,Droplet size - Abstract
We present here a new method for controlling the droplet size in step emulsification processes on a centrifugal microfluidic platform, which, in addition to the centrifugal force, uses pneumatic actuation for fluid displacement. We highlight the importance of the interplay between buoyancy effects and the flow rate at the step junction, and provide a simple analytical model relating these two quantities to the size of the droplets. Numerical models as well as experiments with water-in-oil emulsions are performed in support of the proposed model.
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- 2020
12. Epigenetic subtyping of white blood cells using a thermoplastic elastomer-based microfluidic emulsification device for multiplexed, methylation-specific digital droplet PCR
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Jamal Daoud, Alex Boutin, Ljuboje Lukic, Mojra Janta, Lidija Malic, Teodor Veres, Matthias Geissler, and Abdelrahman Elmanzalawy
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02 engineering and technology ,01 natural sciences ,Biochemistry ,T-Lymphocytes, Regulatory ,DNA sequencing ,Analytical Chemistry ,Epigenesis, Genetic ,chemistry.chemical_compound ,Leukocyte Count ,Lab-On-A-Chip Devices ,Electrochemistry ,Environmental Chemistry ,Humans ,Epigenetics ,Spectroscopy ,Chemistry ,010401 analytical chemistry ,Methylation ,DNA ,DNA Methylation ,Microfluidic Analytical Techniques ,021001 nanoscience & nanotechnology ,Molecular biology ,0104 chemical sciences ,Real-time polymerase chain reaction ,CpG site ,Elastomers ,DNA methylation ,CpG Islands ,0210 nano-technology ,Low copy number ,Multiplex Polymerase Chain Reaction - Abstract
Epigenetic markers attract increasing attention for the study of phenotypic variations, which has led to the investigation of cell-lineage DNA methylation patterns that correlate with human leukocyte populations for obtaining counts of white blood cell (WBC) subsets. Current methods of DNA methylation analysis involve genome sequencing or loci-specific quantitative PCR (qPCR). Herein, a multiplexed digital droplet PCR (ddPCR) workflow for determining epigenetic-based WBC differential count is described for the first time. A microfluidic emulsification device fabricated from a commercially available thermoplastic elastomer (e.g., Mediprene) promotes customizability and cost-effectiveness of the methodology, which are prerequisites for translation into clinical and point-of-care diagnostics. Bisulfite-treated DNA from peripheral blood mononuclear cells and whole blood is encapsulated in droplets with ddPCR reagents containing primers and fluorescent hydrolysis probes specific for CpG loci correlated with WBC sub-population types. The method enables multiplexed detection of various methylation sites within a single droplet. Both qPCR and immunofluorescence staining (IF) were conducted to validate the capacity of the ddPCR methodology to accurately determine WBC sub-populations using epigenetic analysis of methylation sites. ddPCR results correlated closely to cell proportions obtained using IF, whereas qPCR significantly underestimated these values for both high and low copy number gene targets.
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- 2019
13. Active pumping and control of flows in centrifugal microfluidics
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Liviu Clime, Lidija Malic, Matthias Geissler, Jamal Daoud, D. Brassard, and Teodor Veres
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active pumping ,sample preparation ,valving ,Computer science ,010401 analytical chemistry ,Microfluidics ,Mechanical engineering ,integration ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Centrifugal microfluidics ,Process automation system ,01 natural sciences ,0104 chemical sciences ,Electronic, Optical and Magnetic Materials ,Flow control (fluid) ,centrifugal microfluidics ,Materials Chemistry ,Metering mode ,Fluidics ,0210 nano-technology ,Actuator ,Instrument design ,automation - Abstract
This review is an account of centrifugal microfluidic systems that use various actuation strategies in addition to intrinsic centrifugal forces to accurately regulate the motion of fluids during rotation. Platforms that integrate active methods of pumping and flow control render centrifugal microfluidics more versatile as they facilitate integration and process automation by enabling (or improving the reliability of) important fluidic functions, such as metering, aliquoting, valving, flow switching, mixing, and inward pumping. Principles and working mechanisms underlying these strategies are described in the context of recent trends in instrument design and development where centrifugal platforms have been equipped with pneumatic, magnetic or electromechanical actuators serving as pumping and valving elements. The potential of these platforms to perform complex bioanalytical assays in an automated fashion is illustrated by several examples, which include on-chip preparation of aliquot libraries, nucleic acid purification, amplification and analysis as well as blood separation.
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- 2019
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14. SM1.1 - Microfluidic-Based Platforms for Biological Assays Automation in Life-Sciences Research and Remote Medical Applications
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Daniel Brassard, Lidija Malic, Liviu Clime, D. Charlebois, Teodor Veres, N. Buckley, Jamal Daoud, and Matthias Geissler
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Computer science ,business.industry ,Microfluidics ,Nanotechnology ,business ,Automation - Published
- 2018
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15. Designed Biointerface Using Near-Infrared Quantum Dots for Ultrasensitive Surface Plasmon Resonance Imaging Biosensors
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Lidija Malic, Marinella G. Sandros, and Maryam Tabrizian
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chemistry.chemical_classification ,Spectroscopy, Near-Infrared ,Base Sequence ,Biomolecule ,Surface plasmon ,Near-infrared spectroscopy ,DNA, Single-Stranded ,Nanotechnology ,Biointerface ,Biosensing Techniques ,Prostate-Specific Antigen ,Surface Plasmon Resonance ,Analytical Chemistry ,chemistry ,Limit of Detection ,Quantum dot ,Quantum Dots ,Spontaneous emission ,Surface plasmon resonance ,Biosensor ,DNA Primers - Abstract
The surface plasmon resonance imaging chip biointerface is fully designed using near-infrared (NIR) quantum dots (QDs) for the enhancement of surface plasmon resonance imaging (SPRi) signals in order to extend their application for medical diagnostics. The measured SPRi detection signal following the QD binding to the surface was amplified 25-fold for a 1 nM concentration of single-stranded DNA (ssDNA) and 50-fold for a 1 μg/mL concentration of prostate-specific antigen (PSA), a cancer biomarker, thus substantiating their wide potential to study interactions of a diverse set of small biomolecules. This significant enhancement is attributed to the QD's mass-loading effect and spontaneous emission coupling with propagating surface plasmons, which allowed the SPRi limit of detection to be reduced to 100 fM and 100 pg/mL for ssDNA and PSA, respectively. Furthermore, this study illustrates the potential of SPRi to be easily integrated with fluorescent imaging for advanced correlative surface-interaction analysis.
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- 2011
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16. Biochip functionalization using electrowetting-on-dielectric digital microfluidics for surface plasmon resonance imaging detection of DNA hybridization
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Maryam Tabrizian, Teodor Veres, and Lidija Malic
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Microfluidics ,Biomedical Engineering ,Biophysics ,Nanotechnology ,Sensitivity and Specificity ,Electrochemistry ,Digital microfluidics ,Surface plasmon resonance ,Biochip ,In Situ Hybridization ,Oligonucleotide Array Sequence Analysis ,chemistry.chemical_classification ,Biomolecule ,Hybridization probe ,Surface plasmon ,Reproducibility of Results ,Signal Processing, Computer-Assisted ,Equipment Design ,Sequence Analysis, DNA ,General Medicine ,Microfluidic Analytical Techniques ,Surface Plasmon Resonance ,Equipment Failure Analysis ,chemistry ,Wettability ,Electrowetting ,Microelectrodes ,Biotechnology - Abstract
This work reports on a dynamically configurable micro-array surface plasmon resonance biochip platform. The platform comprises a digital electrowetting-on-dielectric (EWOD) microfluidic device tailored to surface plasmon resonance imaging (SPRi). We demonstrate its application for simultaneous immobilization of different DNA probes at the designated detection sites on-chip from sub-microL volume solutions in combination with multichannel label-free real-time detection of subsequent hybridization reactions. Successful on-chip DNA probe dilution and immobilization is also demonstrated using SPRi hybridization detection. Furthermore, active control of the immobilized probe density and orientation is achieved under an applied potential using the electric interface of the EWOD device. For low probe densities, under negative applied potential, the DNA hybridization efficiency is enhanced compared to passive probe immobilization, yielding a two-fold SPR signal increase within only 8min of hybridization. EWOD microfluidic platform coupled with SPRi promises to dramatically increase the speed of detection and quantification of biomolecular interactions while reducing reagent consumption. The proposed system would enable the development of high-throughput, rapid and ultrasensitive detection of biomolecules beyond DNA microarray applications.
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- 2009
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17. Integrated miniaturized optical detection platform for fluorescence and absorption spectroscopy
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Andrew G. Kirk and Lidija Malic
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Detection limit ,Materials science ,Microchannel ,Fabrication ,Absorption spectroscopy ,Silicon ,business.industry ,Metals and Alloys ,chemistry.chemical_element ,Substrate (electronics) ,Condensed Matter Physics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Optics ,chemistry ,Electrical and Electronic Engineering ,Absorption (electromagnetic radiation) ,business ,Instrumentation ,Alexa Fluor - Abstract
This paper presents the design and fabrication of a miniaturized optical detection system for sensing in microchannels, based on integrated optical waveguide technology. This design allows the implementation of both absorption and fluorescence measurement schemes and can be potentially integrated into a lab-on-a-chip system. An array of optical waveguides were fabricated in spin-on polymer technology on a silicon substrate and monolithically integrated with the microfluidic channel and V-groove fibre alignment scheme. The design was adapted to achieve minimum optical losses under the imposed fabrication constraints. Total system losses with a water filled microchannel were experimentally determined to be 10.45 dB. Both fluorescence and absorption detection capabilities of the fabricated device were demonstrated using Alexa Fluor 633 dye, and the corresponding detection limits were found to be 10 nM and 1 μM, respectively. Several areas of improvements in the device design and fabrication have been identified for future works towards better integration for lab-on-a-chip system.
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- 2007
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18. Current State of Intellectual Property in Microfluidic Nucleic Acid Analysis
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Lidija Malic, Maryam Tabrizian, Marc Herrmann, and Xuyen D. Hoa
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Nucleic acid quantitation ,Microfluidics ,General Engineering ,Nanotechnology ,Lab-on-a-chip ,Intellectual property ,Biology ,Commercialization ,law.invention ,Software portability ,law ,Nucleic acid ,Biochemical engineering ,State (computer science) - Abstract
The development of novel fabrication methods, materials and surface chemistries to implement nucleic acid analysis brings reduced cost, reduced reagent consumption, increased analysis efficiency, portability, ease of use and reliability to today's genomic approach. This trend, as evident by the exponential growth in the number of patent applications, granted patents and commercialized systems, is motivated by the promise for significant breakthroughs and benefits of nucleic acid analysis to drug discovery and point-of-care diagnosis. This review paper aims at identifying the enabling technologies and key patents in microfluidics for nucleic acid analysis. In particular, it seeks to identify granted and pending patents for cell sorting and lysis, nucleic acid extraction and purification, followed by nucleic acid amplification, separation and detection. Additionally, it presents an overview of the current intellectual property environment and seeks to identify trends for the future development. Much of this development is geared increasingly toward fully integrated systems. The convergence of technology and interdisciplinary interests is expected to foster further breakthroughs and commercialization.
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- 2007
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19. Polymer-based microfluidic chip for rapid and efficient immunomagnetic capture and release of Listeria monocytogenes
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Nathalie Corneau, Alex Boutin, Jeffrey M. Farber, Christian C. Luebbert, Xuefeng Zhang, Sabah Bidawid, D. Brassard, Liviu Clime, V. Barrere, Lidija Malic, Jamal Daoud, and Teodor Veres
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Materials science ,Polymers ,Surface Properties ,Microfluidics ,Biomedical Engineering ,Nanoparticle ,Bioengineering ,Nanotechnology ,Immunomagnetic separation ,medicine.disease_cause ,Biochemistry ,Listeria monocytogenes ,Lab-On-A-Chip Devices ,medicine ,Sample preparation ,chemistry.chemical_classification ,Microbial Viability ,Immunomagnetic Separation ,Temperature ,General Chemistry ,Polymer ,Equipment Design ,chemistry ,Remanence ,Magnetic nanoparticles ,Nanoparticles - Abstract
Infections caused by foodborne pathogens such as Listeria monocytogenes pose a threat to public health while timely detection is challenging due to pathogen low numbers. The development of robust and efficient sample preparation techniques is crucial to improve detection sensitivity and workflow. Immunomagnetic separation using magnetic nanoparticles (MNPs) is attractive, as it can efficiently capture target cells. For food safety applications, a platform is needed to rapidly process large sample volumes, allowing capture and release of target bacteria conjugated to immunomagnetic nanoparticles (IMNPs). Herein, we demonstrate a method for magnetic capture and release of bacteria-IMNPs complex based on a 3D magnetic trap integrated on a polymeric microfluidic device. The 3D magnetic capture region consist of a dense array of high-aspect ratio (3 : 1) cylindrical pillars embossed in thermoplastic polymer and coated with soft ferromagnetic nickel by an electroless deposition technique. This allows the generation of strong and switchable magnetic capture regions due to the very low remanence of the nickel shell. We propose and validate an optimized configuration of capture regions for efficient localized capture and rapid release of MNPs and IMNPs conjugated to L. monocytogenes. A maximum recovery rate for MNPs corresponded to 91% while a maximum capture efficiency of 30% was obtained for live bacteria, with a minimum detectable sample concentration of ~10 cfu ml(-1) in 1 ml volume using plate-culture method. We believe that the flexible design and low-cost fabrication process of the proposed system will allow rapid sample preparation for applications beyond food and water safety, including point-of-care diagnosis.
- Published
- 2015
20. Nanoporous twinned PtPd with highly catalytic activity and stability
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Teodor Veres, Federico Rosei, Pengfei Guan, Michel L. Trudeau, Lidija Malic, and Xuefeng Zhang
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Materials science ,Low coordination ,Context (language use) ,Nanotechnology ,Structure/function relationships ,Electrochemistry ,Catalysis ,chemistry.chemical_compound ,Theoretical simulation ,General Materials Science ,Platinum ,Catalytic performance ,Sustainable materials ,Decomposition ,Decomposition strategy ,Renewable Energy, Sustainability and the Environment ,Nanoporous ,Electrooxidation ,General Chemistry ,Catalytic oxidation ,Mass activity ,Energy efficiency ,chemistry ,Catalyst activity ,Methanol ,Crystal twinning ,Palladium - Abstract
Growing needs for highly efficient energy storage devices have prompted increasing research efforts in energy-efficient and sustainable materials. In this context, nanoporous noble metals have been studied extensively because of their extraordinary properties. However, existing electrochemical/chemical dealloying approaches for their synthesis largely lack the ability to optimize their structure/function relationships. To overcome this limitation, we developed a thermal-decomposition strategy for the synthesis of component-controllable nanoporous PtPd alloys composed of ∼2 nm sawtooth-like ligaments induced by a high density of twinning boundaries (boundary spacing ∼ 1 nm). Such twinned and ultrathin ligaments exhibit large curvatures between concave and convex regions, associated with abundant low-coordination surface atomic steps and kinks. These low-coordination atoms are sites of high catalytic activity, as confirmed by theoretical simulations. The optimized Pt25Pd75 sample exhibits the best catalytic performance among all the currently reported catalysts, and has a mass activity of 1110 mA mg−1Pt−1 and high stability for the electro-oxidation of methanol.
- Published
- 2015
21. From cellular lysis to microarray detection, an integrated thermoplastic elastomer (TPE) point of care Lab on a Disc
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Teodor Veres, Michel G. Bergeron, Maurice Bossinot, Marc J. Madou, Régis Peytavi, Emmanuel Roy, Lidija Malic, Gale Stewart, Liviu Clime, and Maxence Mounier
- Subjects
DNA, Bacterial ,Materials science ,Nucleic acid quantitation ,polymerase chain reaction ,Microfluidics ,Biomedical Engineering ,Bioengineering ,Nanotechnology ,thermoplastic elastomer ,bacterial spore ,Molding (process) ,Biochemistry ,Buffer (optical fiber) ,plastic ,molecular diagnosis ,Fluidics ,Thermoplastic elastomer ,Point of care ,Oligonucleotide Array Sequence Analysis ,elastomer ,lysis ,nucleic acid analysis ,biology ,industrialization ,General Chemistry ,DNA ,Carbocyanines ,Microfluidic Analytical Techniques ,Bacillus atrophaeus ,biology.organism_classification ,food safety ,Elastomers ,microarray analysis ,microfluidic analysis ,bacterial gene ,Bacillus subtilis - Abstract
We present an all-thermoplastic integrated sample-to-answer centrifugal microfluidic Lab-on-Disc system (LoD) for nucleic acid analysis. The proposed CD system and engineered platform were employed for analysis of Bacillus atrophaeus subsp. globigii spores. The complete assay comprised cellular lysis, polymerase chain reaction (PCR) amplification, amplicon digestion, and microarray hybridization on a plastic support. The fluidic robustness and operating efficiency of the assay were ensured through analytical optimization of microfluidic tools enabling beneficial implementation of capillary valves and accurate control of all flow timing procedures. The assay reliability was further improved through the development of two novel microfluidic strategies for reagents mixing and flow delay on the CD platform. In order to bridge the gap between the proof-of-concept LoD and production prototype demonstration, low-cost thermoplastic elastomer (TPE) was selected as the material for CD fabrication and assembly, allowing the use of both, high quality hot-embossing and injection molding processes. Additionally, the low-temperature and pressure-free assembly and bonding properties of TPE material offer a pertinent solution for simple and efficient loading and storage of reagents and other on-board components. This feature was demonstrated through integration and conditioning of microbeads, magnetic discs, dried DNA buffer reagents and spotted DNA array inserts. Furthermore, all microfluidic functions and plastic parts were designed according to the current injection mold-making knowledge for industrialization purposes. Therefore, the current work highlights a seamless strategy that promotes a feasible path for the transfer from prototype toward realistic industrialization. This work aims to establish the full potential for TPE-based centrifugal system as a mainstream microfluidic diagnostic platform for clinical diagnosis, water and food safety, and other molecular diagnostic applications.
- Published
- 2015
22. Two-dimensional droplet-based surface plasmon resonance imaging using electrowetting-on-dielectric microfluidics
- Author
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Lidija Malic, Maryam Tabrizian, and Teodor Veres
- Subjects
Surface Properties ,Chemistry ,Microfluidics ,Sample processing ,Biomedical Engineering ,Bioengineering ,Nanotechnology ,Equipment Design ,General Chemistry ,Dielectric ,Surface Plasmon Resonance ,Chip ,Biochemistry ,Surface plasmon resonance imaging ,Wettability ,Electrowetting ,Wetting ,Surface plasmon resonance ,Electrodes - Abstract
This article presents a multichannel droplet-based surface plasmon resonance platform. The platform comprises a digital electrowetting-on-dielectric (EWOD) microfluidic device coupled to surface plasmon resonance imaging (SPRi). SPRi is now a well-established detection technique that enables in-situ monitoring of multiple reactions occurring at the surface of the chip without the use of labels. Currently, the limiting factor in the application of SPRi for high-throughput applications is the flow-cell technology which relies on sequential sample processing within the continuous fluid flow. An original solution compared to the continuous flow-cell technology is proposed to increase the capability of existing SPRi technology. A parallel SPRi detection of different samples on the surface is achieved using the array-based digital microfluidic device.
- Published
- 2009
- Full Text
- View/download PDF
23. Advanced EWOD-based digital microfluidic system for multiplexed analysis of biomolecular interactions
- Author
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Teodor Veres, Caroline Miville-Godin, Lidija Malic, François Normandin, and D. Brassard
- Subjects
Materials science ,Fabrication ,Molecular biophysics ,Microfluidics ,Nanotechnology ,Concentration gradient ,Multiplexing - Abstract
This paper presents a low-cost technique for the fabrication of complex electrowetting-on-dielectric (EWOD) digital microfluidic devices. Using this original technology, we have developed devices in which 560 electrodes are used to mix and split nl-size liquid droplets and transport them to 100 analysis spots patterned on a disposable plastic top plate. We demonstrate the multiplexing capability of the developed devices by creating on-chip arrays of droplets with various concentration gradients. Finally, automated biomolecular immobilization and hybridization assays are performed in nl-size droplets under numerous conditions simultaneously with only a limited number of stock solutions., 24th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2011), Jan. 23-27, 2011, Cancun, Mexico
- Published
- 2011
24. Nanostructured digital microfluidics for enhanced surface plasmon resonance imaging
- Author
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Maryam Tabrizian, Teodor Veres, and Lidija Malic
- Subjects
Analyte ,Materials science ,Digital microfluidics ,DNA hybridization ,Microfluidics ,Biomedical Engineering ,Biophysics ,Wetting ,Nanotechnology ,Biosensing Techniques ,Electromagnetic properties ,Signal ,electromagnetic field ,Surface plasmon resonance imaging ,Fluidic interconnects ,Prognostic indicators ,Electrochemistry ,Fluidics ,Surface Plasmon Resonance imaging ,Flow cells ,In Situ Hybridization, Fluorescence ,Detection limit ,Infectious disease ,DNA biochips ,Signal Processing, Computer-Assisted ,General Medicine ,Equipment Design ,Microfluidic Analytical Techniques ,Surface Plasmon Resonance ,Diagnostic applications ,Nanostructures ,Equipment Failure Analysis ,Enhanced surface ,Fluidic manipulation ,nanofabrication ,genetic disorder ,Drop formation ,Biosensor ,Biotechnology - Abstract
The advances in genomics and proteomics have unveiled an exhaustive catalogue of biomarkers that can potentially be used as diagnostic and prognostic indicators of genetic and infectious diseases. Current thrust in biosensor development is towards rapid, real-time, label-free and highly sensitive detection of the indicative biomarkers. While surface plasmon resonance imaging (SPRi) biosensors could potentially be the best suited candidate for biomarker-based diagnosis, important milestones need to be reached. Commercially available SPRi instrumentation is currently limited by the flow-cell technology to serial-sample processing and has limited sensitivity for the detection of markers present at low concentration. In this paper, we have implemented an approach to enhance sample handling and increase the sensitivity of the SPRi detection technique. We have developed a digital microfluidic platform with an integrated nanostructured biosensor interface that allows for rapid, ultra-low volume, sensitive, and automated on-chip SPRi detection of DNA hybridization reactions. Through the exploitation of electromagnetic properties of nanofabricated periodic gold nanoposts, SPRi signal was increased by 200% with the estimated limit of detection of 500. pM (90 attomoles). Using the versatile fluidic manipulation provided by the digital microfluidics, rapid and parallel target identification was achieved on multiple array elements within 1. min using 180. nL sample volume. By delivering multiple target analytes in individually addressable low volume droplets, without external pumps and fluidic interconnects, the overall assay time, cost and complexity was reduced. The proposed platform allows extreme versatility in the manipulation of precious low volume samples which makes this technology very suitable for diagnostic applications. © 2010 Elsevier B.V.
- Published
- 2010
25. Integration and detection of biochemical assays in digital microfluidic LOC devices
- Author
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Maryam Tabrizian, D. Brassard, Teodor Veres, and Lidija Malic
- Subjects
Flexibility (engineering) ,Engineering ,business.industry ,Process (engineering) ,Biochemical Phenomena ,media_common.quotation_subject ,Microfluidics ,Biomedical Engineering ,Reconfigurability ,Bioengineering ,General Chemistry ,Microfluidic Analytical Techniques ,Biochemistry ,Software portability ,Embedded system ,Hardware_INTEGRATEDCIRCUITS ,Humans ,Fluidics ,Digital microfluidics ,Function (engineering) ,business ,media_common - Abstract
The ambition of lab-on-a-chip (LOC) systems to achieve chip-level integration of a complete analytical process capable of performing a complex set of biomedical protocols is hindered by the absence of standard fluidic components able to be assembled. As a result, most microfluidic platforms built to date are highly specialized and designed to fulfill the requirements of a single particular application within a limited set of operations. Electrowetting-on-dielectric (EWOD) digital microfluidic technology has been recently introduced as a new methodology in the quest for LOC systems. Herein, unit volume droplets are manipulated along electrode arrays, allowing a microfluidic function to be reduced to a set of basic operations. The highly reprogrammable architecture of these systems can satisfy the needs of a diverse set of biochemical assays and ensure reconfigurability, flexibility and portability between different categories of applications and requirements. While important progress was made over past years in the fabrication, miniaturization and function programming of the basic EWOD fluidic operations, the success of this technology will in great part depend on the ability of researchers to couple or integrate digital microfluidics to detection approaches that can make the system competitive for LOC applications. The detection techniques should be able to circumvent the limitations of hydrophobic surfaces and exploit the advantages of the array format, high droplet transport speeds and rapid mixing schemes. This review provides an in-depth look at recent developments for the coupling and integration of detection techniques with digital microfluidic platforms for bio-chemical applications.
- Published
- 2010
26. Enhanced surface plasmon resonance imaging detection of DNA hybridization on periodic gold nanoposts
- Author
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Maryam Tabrizian, Lidija Malic, Teodor Veres, and Bo Cui
- Subjects
Nanostructure ,Materials science ,business.industry ,Scanning electron microscope ,Surface plasmon ,DNA, Single-Stranded ,Nucleic Acid Hybridization ,Nanotechnology ,Biosensing Techniques ,DNA ,Surface Plasmon Resonance ,Image Enhancement ,Microscopy, Atomic Force ,Atomic and Molecular Physics, and Optics ,Nanostructures ,Kinetics ,Optics ,Microscopy, Electron, Scanning ,Gold ,Thin film ,Surface plasmon resonance ,business ,Rigorous coupled-wave analysis ,Biosensor ,Lithography - Abstract
We explore periodic gold nanoposts as substrates for the enhanced surface plasmon resonance imaging (SPRi) detection of DNA hybridization. Rigorous coupled-wave analysis was used to model and design the nanopost-based SPRi biosensor. Arrayed gold nanoposts on gold-coated glass substrate, with various widths and periodicity, were fabricated using electron-beam lithography and characterized with scanning electron and atomic force microscopy. A scanning-angle SPRi apparatus was used to conduct the kinetic analysis of DNA hybridization on nanopost-based sensor surface and assess the corresponding SPR signal amplification. Experimental results showed that both the nanostructure size and period influenced the SPR signal enhancement; the optimized 30 nm height, 50 nm size, and 110 nm period nanoposts provided a fivefold SPR signal amplification compared with the plain 50 nm thick gold film used as control.
- Published
- 2007
27. Nanoimprinted plastic substrates for enhanced surface plasmon resonance imaging detection
- Author
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Maryam Tabrizian, Teodor Veres, Lidija Malic, and Bo Cui
- Subjects
Materials science ,business.industry ,Scanning electron microscope ,Gold film ,Surface plasmon ,Reproducibility of Results ,Nanotechnology ,DNA ,Equipment Design ,Surface Plasmon Resonance ,Sensitivity and Specificity ,Atomic and Molecular Physics, and Optics ,Nanostructures ,Equipment Failure Analysis ,Refractometry ,Optics ,Surface plasmon resonance imaging ,Computer-Aided Design ,Surface plasmon resonance ,business ,Rigorous coupled-wave analysis ,Plastics ,Refractive index ,Lithography - Abstract
Periodic nanostructures fabricated by Nanoimprint Litography (NIL) in low-cost plastic substrates and coated with thin gold film were explored for enhanced surface plasmon resonance imaging (SPRi) detection. Rigorous coupled-wave analysis was used to model the SPRi response of these nanostructured surfaces. Two-dimensional nanogratings and nanogrooves were fabricated on Zeonor 1060R(TM) by NIL and followed by metal deposition. The detection of refractive index changes in the dielectric layer due to bulk medium change, DNA immobilization and DNA hybridization events were monitored using SPRi to assess the corresponding signal amplification. The results indicate target-dependent sensitivity enhancement which is maximized for the detection of biomolecular binding events. The 500 nm period nanogrooves provided a 4 times SPR signal amplification compared to the conventional uniform gold film on SF-11 glass for DNA hybridization detection. Our work demonstrates that the use of nanoimprinted plastic substrates provides a low-cost solution for the SPR-based detection with sensitivity that meets the requirements in practical diagnostic applications.
- Published
- 2009
- Full Text
- View/download PDF
28. Water-oil core-shell droplets for electrowetting-based digital microfluidic devices
- Author
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Maryam Tabrizian, François Normandin, D. Brassard, Teodor Veres, and Lidija Malic
- Subjects
Materials science ,Surface Properties ,fluidic operations ,Microfluidics ,Thin layer ,Biomedical Engineering ,Water ,Electrons ,Bioengineering ,Nanotechnology ,General Chemistry ,Microfluidic Analytical Techniques ,Biochemistry ,electrowetting-on-dielectric (EWOD) ,Silicone oil ,Core shell ,chemistry.chemical_compound ,chemistry ,Electrowetting ,digital microfluidic device ,Fluidics ,Digital microfluidics ,Oils ,Voltage - Abstract
available, unlimited, public
- Published
- 2008
- Full Text
- View/download PDF
29. Integration and detection of biochemical assays in digital microfluidic LOC devices.
- Author
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Lidija Malic, Daniel Brassard, Teodor Veres, and Maryam Tabrizian
- Subjects
- *
MICROFLUIDIC devices , *SYSTEMS on a chip , *DIELECTRIC devices , *HYDROPHOBIC surfaces , *BIOCHEMISTRY technique , *BIOLOGICAL assay , *MICROFABRICATION - Abstract
The ambition of lab-on-a-chip (LOC) systems to achieve chip-level integration of a complete analytical process capable of performing a complex set of biomedical protocols is hindered by the absence of standard fluidic components able to be assembled. As a result, most microfluidic platforms built to date are highly specialized and designed to fulfill the requirements of a single particular application within a limited set of operations. Electrowetting-on-dielectric (EWOD) digital microfluidic technology has been recently introduced as a new methodology in the quest for LOC systems. Herein, unit volume droplets are manipulated along electrode arrays, allowing a microfluidic function to be reduced to a set of basic operations. The highly reprogrammable architecture of these systems can satisfy the needs of a diverse set of biochemical assays and ensure reconfigurability, flexibility and portability between different categories of applications and requirements. While important progress was made over past years in the fabrication, miniaturization and function programming of the basic EWOD fluidic operations, the success of this technology will in great part depend on the ability of researchers to couple or integrate digital microfluidics to detection approaches that can make the system competitive for LOC applications. The detection techniques should be able to circumvent the limitations of hydrophobic surfaces and exploit the advantages of the array format, high droplet transport speeds and rapid mixing schemes. This review provides an in-depth look at recent developments for the coupling and integration of detection techniques with digital microfluidic platforms for bio-chemical applications. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
30. Water-oil core-shell droplets for electrowetting-based digital microfluidic devices.
- Author
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Daniel Brassard, Lidija Malic, François Normandin, Maryam Tabrizian, and Teodor Veres
- Subjects
- *
MICROFLUIDICS , *DIGITAL technology , *SILICONES , *FLUID dynamics , *ORGANOSILICON compounds , *SCIENTIFIC apparatus & instruments - Abstract
Digital microfluidics based on electrowetting-on-dielectric (EWOD) has recently emerged as one of the most promising technologies to realize integrated and highly flexible lab-on-a-chip systems. In such EWOD-based digital microfluidic devices, the aqueous droplets have traditionally been manipulated either directly in air or in an immiscible fluid such as silicone oil. However, both transporting mediums have important limitations and neither offers the flexibility required to fulfil the needs of several applications. In this paper, we report on an alternative mode of operation for EWOD-based devices in which droplets enclosed in a thin layer of oil are manipulated in air. We demonstrate the possibility to perform on-chip the fundamental fluidic operations by using such water–oil core–shell droplets and compare systematically the results with the traditional approach where the aqueous droplets are manipulated directly in air or oil. We show that the core–shell configuration combines several advantages of both the air and oil mediums. In particular, this configuration not only reduces the operation voltage of EWOD-based devices but also leads to higher transport velocities when compared with the manipulation of droplets directly in air or oil. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
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