604 research outputs found

    Design and Investigation of Reflectivity based Optofluidic Devices

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    Ph.DDOCTOR OF PHILOSOPH

    Fabrication of Microfluidic Devices for Emulsion Formation by Microstereolithography

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    Droplet microfluidics—the art and science of forming droplets—has been revolutionary for high-throughput screening, directed evolution, single-cell sequencing, and material design. However, traditional fabrication techniques for microfluidic devices suffer from several disadvantages, including multistep processing, expensive facilities, and limited three-dimensional (3D) design flexibility. High-resolution additive manufacturing—and in particular, projection micro-stereolithography (PµSL)—provides a promising path for overcoming these drawbacks. Similar to polydimethylsiloxane-based microfluidics 20 years ago, 3D printing methods, such as PµSL, have provided a path toward a new era of microfluidic device design. PµSL greatly simplifies the device fabrication process, especially the access to truly 3D geometries, is cost-effective, and it enables multimaterial processing. In this review, we discuss both the basics and recent innovations in PµSL; the material basis with emphasis on custom-made photopolymer formulations; multimaterial 3D printing; and, 3D-printed microfluidic devices for emulsion formation as our focus application. Our goal is to support researchers in setting up their own PµSL system to fabricate tailor-made microfluidics

    Optical Printing of Multiscale Hydrogel Structures

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    Hydrogel has been a promising candidate to recapitulate the chemical, physical and mechanical properties of natural extracellular matrix (ECM), and they have been widely used for tissue engineering, lab on a chip and biophotonics applications. A range of optical fabrication technologies such as photolithography, digital projection stereolithography and laser direct writing have been used to shape hydrogels into structurally complex functional devices and constructs. However, it is still greatly challenging for researchers to design and fabricate multiscale hydrogel structures using a single fabrication technology. To address this challenge, the goal of this work is the design and develop novel multimode optical 3D printing technology capable of printing hydrogels with multiscale features ranging from centimeter to micrometer sizes and in the process transforming simple hydrogels into functional devices for many biomedical applications. Chapter 2 presents a new multimode optical printing technology that synergistically combined large-scale additive manufacturing with small-scale additive/subtractive manufacturing. This multiscale fabrication capability was used to (i) align cells using laser induced densification in Chapter 3, (ii) develop diffractive optics based on changes in refractive indices in Chapter 4, (iii) print diffractive optical elements in Chapter 5, and (iv) digitally print complex microfluidic devices and other 3D constructs in Chapter 6. Overall, this work open doors to a new world of fabrication where multiscale functional hydrogel structures are possible for a range biomedical application

    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

    Rapid prototyping of plastic lab-on-a-chip by femtosecond laser micromachining and removable insert microinjection molding

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    We have introduced a new hybrid fabrication method for lab-on-a-chip devices through the combination of femtosecond laser micromachining and removable insert micro-injection molding. This method is particularly suited for the fast prototyping of new devices, while maintaining a competitive low cost. To demonstrate the effectiveness of our approach, we designed, fabricated, and tested a completely integrated flow cytometer coupled to a portable media device. The system operation was tested with fluorescent plastic micro-bead solutions ranging from 100 beads/?L to 500 beads/?L. We demonstrated that this hybrid lab-on-a-chip fabrication technology is suitable for producing low-cost and portable biological microsystems and for effectively bridging the gap between new device concepts and their mass production

    Microfluidic devices interfaced to matrix-assisted laser desorption/ionization mass spectrometry for proteomics

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    Microfluidic interfaces were developed for off-line matrix-assisted laser desorption/ionization mass spectrometry (MALDI). Microfluidic interfaces allow samples to be manipulated on-chip and deposited onto a MALDI target plate for analysis. For this research, microfluidic culturing devices and automated digestion and deposition microfluidic chip platforms were developed for the identification of proteins. The microfluidic chip components were fabricated on a poly(methyl methacrylate), PMMA, wafer using the hot embossing method and a molding tool with structures prepared via micromilling. One of the most important components of the chip system was a trypsin microreactor. An open channel microreactor was constructed in a 100 µm wide and 100 µm deep channel with a 4 cm effective channel length. This device integrated frequently repeated steps for MALDI-based proteomics such as digestion, mixing with a matrix solution, and depositing onto a MALDI target. The microreactor provided efficient digestion of proteins at a flow rate of 1 µL/min with a residence time of approximately 24 s in the reaction channel. An electrokinetically driven microreactor was also developed using a micropost structured chip for digestion. The micropost chip had a higher digestion efficiency due to the higher surface area-to-volume ratio in the channel. Also, the electrokinetic flow eliminated the need for an external pumping system and gave a flat flow profile in the microchannel. The post microreactor consisted of a 4 cm × 200 µm × 50 µm microfluidic channel with trypsin immobilized on an array of 50 µm in diameter micropost support structures with a 50 µm edge-to-edge inter-post spacing. This micropost reactor was also used for fingerprint analysis of whole bacterial cells. The entire tryptic digestion and deposition procedure for intact bacteria took about 1 min. A contact deposition solid-phase bioreactor coupled with MALDI-TOF MS allowed for low-volume fraction deposition with a smaller spot size and a higher local concentration of the analyte. A bacterial cell-culturing chip was constructed for growing cells on-chip followed by off-line MALDI analysis. Coupling MALDI-TOF MS whole cell analysis with microfluidic culturing resulted in more consistent spectra as well as reduction of the total processing time. The microfluidic cell culturing was performed in a PMMA chip with a polydimethylsiloxane (PDMS) cover to allow gas permeation into the culture channel, which contained a 2.1 μL volume active culture chamber. After incubation of E. coli in a microfluidic culture device at 37 ℃ for 24 h, the cultured cells were analyzed with MALDI MS. Also, a microfluidic cell culture device containing continuous perfusion of culture medium was developed using a polycarbonate membrane. This microfluidic culturing format was improved with a fluidic manifold and thermostatted microheaters. Fingerprint mass spectra distinguishing E. coli strains tested were obtained after a 6 h incubation time, which was shorter compared to the 24 h incubation time using conventional culturing techniques. In addition, an enhanced identification procedure for bacteria was achieved by integrating on-chip digestion of cultured bacteria

    Biosensing for the analysis of raw milk

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    Appropriate methods for monitoring raw milk in food sectors are required in order to prevent health-related issues from consuming milk or fermented dairy products such as cheese and yogurt. Conventional systems used for this purpose require sophisticated instruments, highly technical staff and several days to yield an estimated contaminant concentration profile. Currently, there is no technology available for fast and sensitive identification of unwanted substances that evidences several concentration levels in raw milk. As a contribution to the progress of innovative biochemical sensing systems, this thesis presents the design, development and construction of a prototype, which combines the expertise of sensitive immunoassay process with micro total analysis system (µTAS) to identify specific compounds encountered in raw milk. Since the concept of µTAS appeared, the development of microfluidic devices and their application have increased enormously. Microfluidic devices offer a highly efficient platform for analysis of biomolecules due to the capacity for manipulating small amounts of liquid quickly and with high precision. Particle size estimation, particle separation, cell collection, manipulation and cell detection are some of many functions which could be performed through microfluidic systems. Based on these advantages, microfluidic devices in combination with an associated immunoassay system were used in the prototype to concentrate contamination patterns or specific compounds encountered in raw milk. The NANODETECT prototype developed in this thesis should provide an economic, efficient and sensitive platform for multicomponent detection of specific substances in raw milk without requiring sophisticated instruments and trained staff. This thesis was performed for the European project NANODETECT (Development of nanosensors for the detection of quality parameters along the food chain) funded by European Commission within the 7th framework program

    Femtosecond laser microfabricated devices for biophotonic applications

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    Femtosecond Laser DirectWriting has emerged as a key enabling technology for realising miniaturised biophotonic applications offering clear advantages over competing soft-lithography, ion-exchange and sol-gel based fabrication techniques. Waveguide writing and selective etching with three-dimensional design flexibility allows the development of innovative and unprecedented optofluidic architectures using this technology. The work embodied in this thesis focuses on utilising the advantages offered by direct laser writing in fabricating integrated miniaturised devices tailored for biological analysis. The first application presented customised the selective etching phenomenon in fused silica by tailoring the femtosecond pulse properties during the writing process. A device with an embedded network of microchannels with a significant difference in aspect-ratio was fabricated, which was subsequently applied in achieving the high-throughput label-free sorting of mammalian cells based on cytoskeletal deformability. Analysis on the device output cell population revealed minimal effect of the device on cell viability. The second application incorporated an embedded microchannel in fused silica with a monolithically integrated near-infrared optical waveguide. This optofluidic device implemented the thermally sensitive emission spectrum of semiconductor nanocrystals in undertaking remote thermometry of the localised microchannel environment illuminated by the waveguide. Aspects relating to changing the wavelength of illumination from the waveguide were analysed. The effect of incorporating carbon nanotubes as efficient heaters within the microchannel was investigated. Spatio-thermal imaging of the microchannel illuminated by the waveguide revealed the thermal effects to extend over distances appreciably longer than the waveguide cross-section. On the material side of direct laser writing, ultra-high selective etching is demonstrated in the well-known laser crystal Nd:YAG. This work presents Nd:YAG as a material with the potential to develop next-generation optofluidic devices

    Continuous focusing and separation of microparticles with acoustic and magnetic fields

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    Microfluidics enables a diverse range of manipulations (e.g., focusing, separating, trapping, and enriching) of micrometer-sized objects, and has played an increasingly important role for applications that involve single cell biology and the detection and diagnosis of diseases. In microfluidic devices, methods that are commonly used to manipulate cells or particles include the utilization of hydrodynamic effects and externally applied field gradients that induce forces on cells/particles, such as electrical fields, optical fields, magnetic fields, and acoustic fields. However, these conventional methods often involve complex designs or strongly depend on the properties of the flow medium or the interaction between the fluid and fluidic channels, so this dissertation aims to propose and demonstrate novel and low-cost techniques to fabricate microfluidic devices to separate microparticles with different sizes, materials and shapes by the optimized acoustic and magnetic fields. The first method is to utilize acoustic bubble-enhanced pinched flow for microparticle separation; the microfluidic separation of magnetic particles with soft magnetic microstructures is achieved in the second part; the third technique separates and focuses microparticles by multiphase ferrofluid flows; the fourth method realizes the fabrication and integration of microscale permanent magnets for particle separation in microfluidics; magnetic separation of microparticles by shape is proposed in the fifth technique. The methods demonstrated in this dissertation not only address some of the limitations of conventional microdevices, but also provide simple and efficient method for the separation of microparticles and biological cells with different sizes, materials and shapes, and will benefit practical microfluidic platforms concerning micron sized particles/cells --Abstract, page iv
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