379 research outputs found

    Microfluidic Production of Polymeric Functional Microparticles

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    This dissertation focuses on applying droplet-based microfluidics to fabricate new classes of polymeric microparticles with customized properties for various applications. The integration of microfluidic techniques with microparticle engineering allows for unprecedented control over particle size, shape, and functional properties. Specifically, three types of microparticles are discussed here: (1) Magnetic and fluorescent chitosan hydrogel microparticles and their in-situ assembly into higher-order microstructures; (2) Polydimethylsiloxane (PDMS) microbeads with phosphorescent properties for oxygen sensing; (3) Macroporous microparticles as biological immunosensors. First, we describe a microfluidic approach to generate monodisperse chitosan hydrogel microparticles that can be further connected in-situ into higher-order microstructures. Microparticles of the biopolymer chitosan are created continuously by contacting an aqueous solution of chitosan at a microfluidic T-junction with a stream of hexadecane containing a nonionic detergent, followed by downstream crosslinking of the generated droplets by a ternary flow of glutaraldehyde. Functional properties of the microparticles can be easily varied by introducing payloads such as magnetic nanoparticles and/or fluorescent dyes into the chitosan solution. We then use these prepared microparticles as "building blocks" and assemble them into high ordered microstructures, i.e. microchains with controlled geometry and flexibility. Next, we describe a new approach to produce monodisperse microbeads of PDMS using microfluidics. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into soft, solid microbeads. In addition, our technique allows for direct integration of payloads, such as an oxygen-sensitive porphyrin dye, into the PDMS microbeads. We then show that the resulting dye-bearing beads can function as non-invasive and real-time oxygen micro-sensors. Finally, we report a co-flow microfluidic method to prepare uniform polymer microparticles with macroporous texture, and investigate their application as discrete immunological biosensors for the detection of biological species. The matrix of such microparticles is based on macroporous polymethacrylate polymers configured with tailored pores ranging from hundreds of nanometers to a few microns. Subsequently, we immobilize bioactive antibodies on the particle surface, and demonstrate the immunological performance of these functionalized porous microbeads over a range of antigen concentrations

    Koseido purasuchikku maikuro nano kozotai sakusei to kagaku seikagaku maikurochippu eno oyo

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    戶ćșŠ:新 ; 栱摊ç•Șć·:ç”Č3060ć· ; ć­ŠäœăźçšźéĄž:ćšćŁ«(ć·„ć­Š) ; 授䞎ćčŽæœˆæ—„:2010/3/15 ; æ—©ć€§ć­Šäœèš˜ç•Șć·:新532

    Recent advances on open fluidic systems for biomedical applications: A review

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    Microfluidics has become an important tool to engineer microenvironments with high precision, comprising devices and methods for controlling and manipulating fluids at the submillimeter scale. A specific branch of microfluidics comprises open fluidic systems, which is mainly characterized by displaying a higher air/liquid interface when compared with traditional closed-channel setups. The use of open channel systems has enabled the design of singular architectures in devices that are simple to fabricate and to clean. Enhanced functionality and accessibility for liquid handling are additional advantages inputted to technologies based on open fluidics. While benchmarked against closed fluidics approaches, the use of directly accessible channels decreases the risk of clogging and bubble-driven flow perturbation. In this review, we discuss the advantages of open fluidics systems when compared to their closed fluidics counterparts. Platforms are analyzed in two separated groups based on different confinement principles: wall-based physical confinement and wettability-contrast confinement. The physical confinement group comprises both open and traditional microfluidics; examples based on open channels with rectangular and triangular cross-section, suspended microfluidics, and the use of narrow edge of a solid surface for fluid confinement are addressed. The second group covers (super)hydrophilic/(super)hydrophobic patterned surfaces, and examples based on polymer-, textile- and paper-based microfluidic devices are explored. The technologies described in this review are critically discussed concerning devices' performance and versatility, manufacturing techniques and fluid transport/manipulation methods. A gather-up of recent biomedical applications of open fluidics devices is also presented.European Research Council grant agreement ERC-2012-ADG 20120216-321266 for project ComplexiTE and ERC-2014-ADG-669858 for project “ATLAS”. N. M. Oliveira acknowledges the financial support from Portuguese Foundation for Science and Technology − FCT (Grant SFRH/BD/73172/2010), from the financial program POPH/FSE from QREN. The work was developed within the scope of the project CICECO Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013). Sara Vilabril acknowledges the financial support from national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreementinfo:eu-repo/semantics/publishedVersio

    Novel lab-on-a-chip design for biomolecular diagnosis

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    Understanding Flow-Induced Phase Inversion Of Emulsions Using Microfluidics

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    Phase inversion emulsification (PIE) is a process of generating emulsions by inverting the continuous and dispersed phases of precursor emulsions. PIE is particularly useful when it is challenging to generate the target emulsions by conventional emulsification methods. One such case is the synthesis of polymeric nanoparticles, which requires production of very small droplets of viscous oils. Currently most, if not all, PIE processes in industry are performed as batch processes. Many studies have demonstrated considerable reductions in operation time/cost by changing a batch system to a continuous system. One way of inducing phase inversion in continuous processing is by flowing emulsions through precisely engineered channels and pore-arrays i.e. by flow-induced phase inversion emulsification (FIPIE). A clear advantage of this mechanism is that it can be simulated in microfluidic channels and thus direct observation and fundamental investigation of the PIE process is possible. It is shown that preferential wetting between the dispersed phase of the precursor emulsions and the channel surfaces is crucial for FIPIE. This means, O/W emulsions require hydrophobic channels for FIPIE and vice versa. A tapered design of the phase inversion channels (PICs) with homogeneous surface treatments is used to induce FIPIE. It is found that FIPIE is very sensitive to the amount of taper and is suppressed if taper angle increases above 5 degrees. The dynamic factors affecting FIPIE are investigated in terms of dimensionless parameters – Capillary number, which denotes the relative importance of surface tension and viscous effects and D/W, which is the ratio of size of droplets to the minimum width of the tapered PICs. Lower Ca and higher D/W are found to favor FIPIE. A mechanism of FIPIE is proposed based on the real-time visualization of FIPIE. As droplets passed through narrow channels, the continuous aqueous phase is sheared into a thin film surrounding the oil droplets. Rupture of this aqueous film is found to be the most critical mechanistic step of the process. The underlying physical phenomena driving film rupture are studied based on a balance of interfacial stresses. Finally, the effect of composition and molecular mass of surfactants on the stability of emulsions against FIPIE is studied. It is shown that surfactants, which provide thicker and more viscoelastic films at emulsion interfaces result in emulsions that are more resistant to FIPIE. The insights developed in this thesis can further the prospects of enabling continuous PIE on a larger scale

    Surface engineering the cellular microenvironment via patterning and gradients

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    Cell organization, proliferation, and differentiation are impacted by diverse cues present in the cellular microenvironment. As a result, the surface of a material plays an important role in cellular function. Synthetic surfaces may be augmented by physical as well as chemical means. In particular, patterning and interfacial gradients may be utilized to mitigate the cellular response. Patterning is advantageous as it affords control over a range of feature sizes from several nanometers to millimeters. Gradients exist in vivo , for instance in stem cell niches, and the ability to create interfacial gradients in vitro can provide valuable insights into the influence of a series of minute surface changes on a single sample. This review focuses on fabrication methods for generating micro‐ and nanoscale surface patterns as well as interfacial gradients, the impact of these surface modifications on the cellular response, and the advantages and challenges of these surfaces in in vitro applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys., 2013 The influence of patterning and interfacial gradients on the cellular response has numerous applications in tissue engineering and basic cell science. Various methods for fabricating small‐scale patterns and interfacial gradients as well as their potential and limitations are described. Furthermore, the impact of patterns and gradients on cellular function for numerous cell types and the use of these techniques to address biological questions in in vitro environments are illustrated. Future perspectives are also provided.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97492/1/23275_ftp.pd

    Rapid detection of theophylline using an aptamer-based nanopore thin film sensor

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    This paper reports, for the first time, an aptamer-based nanopore thin film sensor for detecting the ophylline in buffer and complex fluids. In my experiments, I created the sensor and found that it could help us to better test theophylline than an antibody-based detection sensor. The following is a detailed explanation of the sensor creation and the experimental process. Anodic aluminum oxide (AAO) has been investigated and applied in numerous products since the 1970s. It is a highly-arrayed porous nanostructure as shown in Figure 1. The pore size normally ranges from tens to hundreds of nanometers, and the aspect ratio could be higher than 40:1. Application areas of AAO include biomedical sensing, energy storage, template-based nanofabrication, electronics, etc. In my experiment, I applied AAO to the process of creating a sensor. In my experiments, I chose RNA aptamer rather than antibodies because its molecules overcome the weakness of antibodies. The 33 nts RNA aptamer sequences used were found to recognize and selectively bind theophylline (Figure 2) [1]. Moreover, aptamers are easy to synthesize, have both excellent heat stability and a wide tolerance range of PH and salt concentration, and is much less costly than antibodies. The first study used an aptamer-based nanopore thin film sensor to detect theophylline in the buffer and complex fluids. I first fabricated the nanopore thin film sensors with a microfluidic interface, then demonstrated the surface functionalization procedure of the sensor. I then used optical transducing signals to detect the fringes followed by using the sensor as a reference sensor to further cancel out the non-specific binding effect; theophylline in low concentration (0.2ÎŒM), caffeine, theobromine, and plant extract were successfully detected. The experiment showed that this aptamer-based sensor had good specificity and selectivity, allowing me to further test theophylline in serum. The second study used an optical aptamer-based plant hormone sensor with a microfluidics capillary interface. I adopted the exact same methodology and sensor from themy first study and further designed an optical aptamer-based sensor with a microfluidics capillary interface to upgrade the testing process. Such a microfluidics capillary interface film censor was created and how my two successful experiments were performed. The research outcome is that an aptamer-based label-free sensor for optically detecting theophylline has been demonstrated for the first time. It performs much better than its competitors and has a promising future in further applications in similar experiments

    Controlling Surface-Induced Platelet Activation by Modulation of Contacting Interfaces

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    BlutplĂ€ttchen, auch Thrombozyten genannt, sind ein wesentlicher Bestandteil des menschlichen Blutgerinnungssystems. Die Hauptaufgabe der Thrombozyten innerhalb des Körpers besteht in der Blutstillung. Außerhalb des Körpers neigen Thrombozyten jedoch dazu, nach kurzem Kontakt mit synthetischen, nicht physiologischen OberflĂ€chen zu aktivieren, was fĂŒr viele Anwendungen unerwĂŒnscht sein kann, einschließlich der Lagerung von Thrombozyten und der Erforschung der Wechselwirkungen zwischen Thrombozyten und Arzneimitteln. Normalerweise werden Thrombozyten-Konzentrate in handelsĂŒblichen Plastikbeuteln aufbewahrt, die eine große Menge an Weichmachern enthalten, um die FlexibilitĂ€t des Beutels zu erhöhen und die Möglichkeit eines Bruchs wĂ€hrend der Handhabung und des Transports zu vermeiden. Bei lĂ€ngerer Exposition können die giftigen Weichmacher in das Thrombozyten-Konzentrat entweichen. Aktivierte Thrombozyten setzen eine Vielzahl von Proteinen frei, die den Prozess der oberflĂ€cheninduzierten Thrombozytenaktivierung (SIPA) weiter unterstĂŒtzen. SIPA ist eines der Hauptprobleme von Medizinprodukten mit Blutkontakt und TransfusionsgerĂ€ten, und ein entscheidender Faktor fĂŒr die verkĂŒrzte Haltbarkeit gelagerter Thrombozyten. Um SIPA zu vermeiden, werden den Thrombozyten-Konzentraten Antikoagulantien zugesetzt, so dass sie bis zu 5 Tage gelagert werden können. Diese Antikoagulantien greifen in die Aktivierungswege der Thrombozyten ein und beeintrĂ€chtigen so ihre FunktionalitĂ€t. Das hĂ€ufigste Problem bei der Lagerung von Thrombozyten ist schließlich die Gefahr einer bakteriellen Kontamination. Um dieses Problem zu lösen, werden verschiedene UV-Behandlungen eingesetzt, um das Risiko einer Kontamination mit Krankheitserregern zu minimieren. Studien zeigen jedoch, dass diese Strahlung mit kurzer WellenlĂ€nge die Bestandteile der Thrombozytenmembran zerstören und zu einer Aktivierung der Thrombozyten fĂŒhren kann. Diese zahlreichen, oft miteinander verknĂŒpften Probleme verdeutlichen den dringenden Bedarf an einer effizienten Lösung zur Optimierung der Lagerungsbedingungen fĂŒr Thrombozyten und zur Maximierung ihrer LagerfĂ€higkeit. Ziel dieser Doktorarbeit ist es, OberflĂ€chen zu entwickeln, die die AdhĂ€sion von Thrombozyten hemmen und somit ihre Aktivierung und Aggregation verhindern - ohne dass der Zusatz von Antikoagulantien erforderlich ist. FĂŒr die VerĂ€nderung der OberflĂ€cheneigenschaften stehen drei verschiedene AnsĂ€tze zur VerfĂŒgung: Biophysikalische, physikochemische oder biochemische Strategien können Verwendet werden, um eine plĂ€ttchenfreundliche OberflĂ€che zu gestalten. In der ersten Phase dieses Projekts wurde eine Kombination aus physikochemischen und biophysikalischen AnsĂ€tzen angewandt, um Hydrogele aus Gelatine und Agarose herzustellen, die anschließend durch Integration von Eisennanopartikeln zu Nanokompositen verarbeitet wurden. Agarose-basierte Hydrogel-Filme erwiesen sich dabei durch die Kombination von OberflĂ€chenbenetzbarkeit und besseren mechanischen Eigenschaften als ideale OberflĂ€chen. Mikroskopaufnahmen zeigten, dass die Anzahl der BlutplĂ€ttchen, die an solchen OberflĂ€chen adhĂ€rieren, deutlich reduziert und die Ausbreitung der BlutplĂ€ttchen verhindert wurde. Hergestellte Agarose-Filme und ihre Nanokomposite konnten darĂŒber hinaus bakterielles Wachstum erfolgreich hemmen: Von allen getesteten Proben wurde der höchste Prozentsatz an toten Bakterien auf den Nanokomposit-Filmen gemessen. Die Topographie des Substrats spielt eine entscheidende Rolle fĂŒr das Verhalten der Zellen und die Kontrolle ihrer Physiologie und Morphologie. FĂŒr die VerĂ€nderung der OberflĂ€chentopografie stehen zahlreiche komplexe Techniken zur VerfĂŒgung. In dieser Arbeit wurden zwei Techniken mit individuellen Vorteilen zur Herstellung von Nanostrukturen eingesetzt. Bei der ersten handelt es sich um ein auf der Rasterkraftmikroskopie (AFM) basierendes Fluidiksystem namens FluidFM, bei dem eine Monomere enthaltende Tinte aus der Öffnung des Cantilever Spitze auf die OberflĂ€che extrudiert wird. Nach dem Druckvorgang wird die Tinte polymerisiert, um 3D-Strukturen zu erhalten. Mit Hilfe von kontinuierlichen und diskontinuierlichen Topografien wurden hexagonale Bienenstock- bzw. halbkugelförmige Gitterstrukturen hergestellt. Dabei zeigte sich, dass die Thrombozyten diese Strukturierung mechanisch wahrnehmen und ihr Zytoskelett umorganisieren, was zu einer geringeren Ausbreitung der BlutplĂ€ttchen fĂŒhrt. DarĂŒber hinaus wurde die Technik zum Drucken einer modifizierten biofunktionalisierten Tinte verwendet, die so modifiziert wurde, dass MolekĂŒle mit unterschiedlichen funktionellen Gruppen in die Basistinte integriert wurden. Diese Modifikation fĂŒhrte nur zu einer geringfĂŒgigen VerĂ€nderung der mechanischen Eigenschaften der gedruckten Strukturen, wĂ€hrend ihre FunktionalitĂ€t erhalten blieb. Die Möglichkeit, Bindungsmotive fĂŒr spezifische Wechselwirkungen zu integrieren, demonstriert die Vielseitigkeit der FluidFM und ebnet den Weg fĂŒr die weitere Erforschung des biochemischen/topographischen Ansatzes im Bereich der Entwicklung plĂ€ttchenfreundlicher OberflĂ€chen. Das Drucken von Mikro- und Nanostrukturen stellt eine schnelle, kostengĂŒnstige und effiziente Methode zur Herstellung verschiedener geometrischer Prototypen dar und kann nicht nur zur Untersuchung verschiedener Strukturformen, sondern auch ihrer GrĂ¶ĂŸe und anderer topografischer Parameter eingesetzt werden. Die zweite verwendete Technik war die thermische Nanoimprint-Lithografie (T-NIL), mit der ein breiteres Spektrum an OberflĂ€chentopologien untersucht werden konnte, einschließlich Punkt, Kette, Pille und Quadrat-förmiger. Diese Nanomuster wurden auf Siliziumscheiben geĂ€tzt und auf einen PDMS-basierten Stempel ĂŒbertragen, der so zum PrĂ€gen von Hydrogelen verwendet werden konnte. Verschiedene Topologien wurden auf die OberflĂ€che von Agarosegelen geprĂ€gt, um ihre zuvor beobachtete, hemmende Wirkung auf die ThrombozytenadhĂ€sion zu verbessern. Das pillenförmige Nanomuster war dabei am besten geeignet, um die ThrombozytenadhĂ€sion zu hemmen, was auf die Höhe der Struktur zurĂŒckgefĂŒhrt werden kann. Zusammenfassend lĂ€sst sich festhalten, dass in diesem Projekt Hydrogelfilme auf Agarosebasis, insbesondere in Form von Nanokompositen mit integrierten antibakteriellen Eisennanopartikeln, entwickelt wurden, die Lagerungsbedingungen fĂŒr Thrombozyten deutlich verbessern, indem sie die SIPA und das Risiko einer bakteriellen Kontamination verringern. UV-Behandlungen von Thrombozyten-Konzentraten werden dadurch ĂŒberflĂŒssig. Durch die EinfĂŒhrung verschiedener OberflĂ€chentopologien kann die AdhĂ€sion von Thrombozyten gehemmt werden: Das FluidFM-basierte vielseitig einsetybare Nanodrucksystem wurde fĂŒr die Erforschung und Entwicklung von Prototypen effektiver Geometrien eingesetzt, wĂ€hrend T-NIL fĂŒr die PrĂ€gung ausgewĂ€hlter Strukturen auf die OberflĂ€che von Agarose-Filmen verwendet werden kann, um eine einheitliche OberflĂ€chentopographie zu schaffen

    Microfluidics and Nanofluidics Handbook

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    The Microfluidics and Nanofluidics Handbook: Two-Volume Set comprehensively captures the cross-disciplinary breadth of the fields of micro- and nanofluidics, which encompass the biological sciences, chemistry, physics and engineering applications. To fill the knowledge gap between engineering and the basic sciences, the editors pulled together key individuals, well known in their respective areas, to author chapters that help graduate students, scientists, and practicing engineers understand the overall area of microfluidics and nanofluidics. Topics covered include Finite Volume Method for Numerical Simulation Lattice Boltzmann Method and Its Applications in Microfluidics Microparticle and Nanoparticle Manipulation Methane Solubility Enhancement in Water Confined to Nanoscale Pores Volume Two: Fabrication, Implementation, and Applications focuses on topics related to experimental and numerical methods. It also covers fabrication and applications in a variety of areas, from aerospace to biological systems. Reflecting the inherent nature of microfluidics and nanofluidics, the book includes as much interdisciplinary knowledge as possible. It provides the fundamental science background for newcomers and advanced techniques and concepts for experienced researchers and professionals
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