| 1. |
- Bengtsson, Katarina
(author)
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Electrokinetic devices from polymeric materials
- 2017
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Doctoral thesis (other academic/artistic)abstract
- There are multiple applications for polymers: our bodies are built of them, plastic bags and boxes used for storage are composed of them, as are the shells for electronics, TVs, computers, clothes etc. Many polymers are cheap, and easy to manufacture and process which make them suitable for disposable systems. The choice of polymer to construct an object will therefore highly influence the properties of the object itself. The focus of this thesis is the application of commonly used polymers to solve some challenges regarding integration of electrodes in electrokinetic devices and 3D printing.The first part of this thesis regards electrokinetic systems and the electrodes’ impact on the system. Electrokinetic systems require Faradaic (electrochemical) reactions at the electrodes to maintain an electric field in an electrolyte. The electrochemical reactions at the electrodes allow electron-to-ion transduction at the electrode-electrolyte interface, necessary to drive a current at the applied potential through the system, which thereby either cause flow (electroosmosis) or separation (electrophoresis). These electrochemical reactions at the electrodes, such as water electrolysis, are usually problematic in analytical systems and systems applied in biology. One solution to reduce the impact of water electrolysis is by replacing metal electrodes with electrochemically active polymers, e.g. poly(3,4-ethylenedioxythiophene) (PEDOT). Paper 1 demonstrates that PEDOT electrodes can replace platinum electrodes in a gel electrophoretic setup. Paper 2 reports an all-plastic, planar, flexible electroosmotic pump which continuously transports water from one side to the other using potentials as low as 0.3 V. This electroosmotic pump was further developed in paper 3, where it was made into a compact and modular setup, compatible with commercial microfluidic devices. We demonstrated that the pump could maintain an alternating flow for at least 96 h, with a sufficient flow of cell medium to keep cells alive for the same period of time.The second part of the thesis describes the use of 3D printers for manufacturing prototypes and the material requirements for 3D printing. Protruding and over-hanging structures are more challenging to print using a 3D printer and usually require supporting material during the printing process. In paper 4, we showed that polyethylene glycol (PEG), in combination with a carbonate-based plasticizer, functions well as a 3D printable sacrificial template material. PEG2000 with between 20 and 30 wt% dimethyl carbonate or propylene carbonate have good shear-thinning rheology, mechanical and chemical stability, and water solubility, which are advantageous for a supporting material used in 3D printing.The advances presented in this thesis have solved some of the challenges regarding electrokinetic systems and prototype manufacturing. Hopefully this will contribute to the development of robust, disposable, low-cost, and autonomous electrokinetic devices.
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| 2. |
- Bengtsson, Martin, et al.
(author)
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Influence of Nonuniform Channel Width Distribution in Porous Silicon High Aspect Ratio Parallel Channel Micro Reactors
- 2005
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In: [Host publication title missing]. - 0854046437 ; 1, s. 629-631
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Conference paper (peer-reviewed)abstract
- The paper focuses on the fact that, since the flow rate in parallel channels relies strongly on the channel width, the combination may lead to inaccurate results if errors in the fabrication process lead to an uneven distribution of channel widths. Parallel channel enzyme reactors were designed with channel widths distributed normally with different degrees of standard deviation. The reactors were then evaluated with regard to dispersion and to catalytic effect of the immobilised enzyme. It was shown that for lower concentrations the catalytic efficiency decreased significantly even for small variations in the distribution of channel widths and reactors with poor homogeneity in channel widths also diluted the sample more than the others.
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| 3. |
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| 4. |
- Ghazal, Aghiad, et al.
(author)
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Direct monitoring of calcium-triggered phase transitions in cubosomes using small-angle X-ray scattering combined with microfluidics
- 2016
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In: Journal of Applied Crystallography. - 0021-8898. ; 49:6, s. 2005-2014
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Journal article (peer-reviewed)abstract
- This article introduces a simple microfluidic device that can be combined with synchrotron small-angle X-ray scattering (SAXS) for monitoring dynamic structural transitions. The microfluidic device is a thiol-ene-based system equipped with 125 μm-thick polystyrene windows, which are suitable for X-ray experiments. The device was prepared by soft lithography using elastomeric molds followed by a simple UV-initiated curing step to polymerize the chip material and simultaneously seal the device with the polystyrene windows. The microfluidic device was successfully used to explore the dynamics of the structural transitions of phytantriol/dioleoylphosphatidylglycerol-based cubosomes on exposure to a buffer containing calcium ions. The resulting SAXS data were resolved in the time frame between 0.5 and 5.5 s, and a calcium-triggered structural transition from an internal inverted-type cubic phase of symmetry Im3m to an internal inverted-type cubic phase of symmetry Pn3m was detected. The combination of microfluidics with X-ray techniques opens the door to the investigation of early dynamic structural transitions, which is not possible with conventional techniques such as glass flow cells. The combination of microfluidics with X-ray techniques can be used for investigating protein unfolding, for monitoring the formation of nanoparticles in real time, and for other biomedical and pharmaceutical investigations. A combination of microfluidics with X-ray techniques has been used to perform dynamic structural studies on nanoparticulate formulations.
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| 5. |
- Ghazal, Aghiad, et al.
(author)
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Microfluidic Platform for the Continuous Production and Characterization of Multilamellar Vesicles : A Synchrotron Small-Angle X-ray Scattering (SAXS) Study
- 2017
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In: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 8:1, s. 73-79
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Journal article (peer-reviewed)abstract
- A microfluidic platform combined with synchrotron small-angle X-ray scattering (SAXS) was used for monitoring the continuous production of multilamellar vesicles (MLVs). Their production was fast and started to evolve within less than 0.43 s of contact between the lipids and the aqueous phase. To obtain nanoparticles with a narrow size distribution, it was important to use a modified hydrodynamic flow focusing (HFF) microfluidic device with narrower microchannels than those normally used for SAXS experiments. Monodispersed MLVs as small as 160 nm in size, with a polydispersity index (PDI) of approximately 0.15 were achieved. The nanoparticles produced were smaller and had a narrower size distribution than those obtained via conventional bulk mixing methods. This microfluidic platform therefore has a great potential for the continuous production of monodispersed NPs.
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| 6. |
- Laurell, Thomas, et al.
(author)
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Lab on a chip: Scandinavia
- 2012
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In: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 12:22, s. 4601-4602
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Journal article (peer-reviewed)
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| 7. |
- Lilliehorn, Tobias, et al.
(author)
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Bioassays on ultrasonically trapped microbead clusters in microfluidic systems
- 2004
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In: Micro Total Analysis Systems 2004. - 0854048960 ; 2, s. 327-329
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Conference paper (peer-reviewed)abstract
- The handling of biochemically functionalised beads or particles is becoming increasingly important in µTAS. Bead-based analysis of e.g. proteins can be made sensitive due to the large active surface area and flexible by chemical design of the bead surface. We have developed a microfluidic device utilising an array of integrated and individually controlled ultrasonic microtransducers for particle trapping [1]. Particles inserted in the device are subjected to acoustic radiation forces [2] confining them at localised trapping sites. We would now, for the first time at an international conference, like to present a technique for performing bioassays on such ultrasonically trapped beads in microfluidic systems. The microfluidic device is shown in Fig. 1, where the piezoceramic ultrasonic transducers can be seen in the channel crossings in the insert. The device is designed as an acoustic resonator, to obtain localised standing acoustic waves at each transducer with essentially one pressure node in the middle of the 72 µm deep channel when operated near 10 MHz. This configuration is chosen to keep trapped particles away from the interior surfaces of the device, thus enabling fast switching of beads with a minimum in carry-over between assays. The fluidic chip, shown in Fig. 2, is designed to allow injection of microbeads, washing fluid and sample to the three trapping sites. It has been shown that the microbead clusters, as shown in Fig. 3, can be trapped at considerably high perfusion rates, up to 10 µl/min, Fig 4. As a model bioassay, 6.7 µm biotin-covered beads (PC-B-6.0, Gerlinde Kisker, Germany) were injected and transported to one tapping site using washing fluid (water). Activating the transducer trapped the beads. A solution of FITC-tagged avidin was perfused over the bead bed at 3 µl/min, using the corresponding orthogonal sample channel. After 100 s the sample flow was turned off and the bead trap was washed by perfusing water at 3 µl/min. The fluorescence response from the trapped bead clusters was monitored during the assay, and the result is shown in Fig. 5. After excess avidin was washed from the bead trap, a measured step response . indicated that avidin had bound to the beads. Finally the possibility of moving trapped microbeads between the individually controlled trapping sites in the device is shown in Fig. 6, where the transducers are activated sequentially while keeping the bead carrying washing fluid at 3 µl/min during the experiment. Work in the near future will be focused on optimising the device with respect to the bioassay performance, and in a longer perspective on expanding the concept to two dimensions to enable a new dynamic mode of generating bioanalytical arrays.
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| 8. |
- Manneberg, Otto, 1981-, et al.
(author)
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Spatial confinement of ultrasonic force fields in microfluidic chips
- 2009
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In: Ultrasonics. - : Elsevier BV. - 0041-624X .- 1874-9968. ; 49, s. 112-119
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Journal article (peer-reviewed)abstract
- We demonstrate and investigate multiple localized ultrasonic manipulation functions in series in microfluidic chips. The manipulation functions are based on spatially separated and confined ultrasonic primary radiation force fields, obtained by local matching of the resonance condition of the microfluidic channel. The channel segments are remotely actuated by the use of frequency-specific external transducers with refracting wedges placed on top of the chips. The force field in each channel segment is characterized by the use of micrometer-resolution particle image velocimetry ( micro-PIV). The confinement of the ultrasonic fields during single-or dual-segment actuation, as well as the cross-talk between two adjacent. fields, is characterized and quantified. Our results show that the field confinement typically scales with the acoustic wavelength, and that the cross-talk is insignificant between adjacent. fields. The goal is to define design strategies for implementing several spatially separated ultrasonic manipulation functions in series for use in advanced particle or cell handling and processing applications. One such proof-of-concept application is demonstrated, where. flow-through-mode operation of a chip with. flow splitting elements is used for two-dimensional pre-alignment and addressable merging of particle tracks.
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| 9. |
- Nilsson, Christian, et al.
(author)
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Nanoparticle-based capillary electroseparation of proteins in polymer capillaries under physiological conditions.
- 2010
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In: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 31:3, s. 459-464
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Journal article (peer-reviewed)abstract
- Totally porous lipid-based liquid crystalline nanoparticles were used as pseudostationary phase for capillary electroseparation with LIF detection of proteins at physiological conditions using unmodified cyclic olefin copolymer capillaries (Topas, 6.7 cm effective length). In the absence of nanoparticles, i.e. in CE mode, the protein samples adsorbed completely to the capillary walls and could not be recovered. In contrast, nanoparticle-based capillary electroseparation resolved green fluorescent protein from several of its impurities within 1 min. Furthermore, a mixture of native green fluorescent protein and two of its single-amino-acid-substituted variants was separated within 2.5 min with efficiencies of 400 000 plates/m. The nanoparticles prevent adsorption by introducing a large interacting surface and by obstructing the attachment of the protein to the capillary wall. A one-step procedure based on self-assembly of lipids was used to prepare the nanoparticles, which benefit from their biocompatibility and suspension stability at high concentrations. An aqueous tricine buffer at pH 7.5 containing lipid-based nanoparticles (2% w/w) was used as electrolyte, enabling separation at protein friendly conditions. The developed capillary-based method facilitates future electrochromatography of proteins on polymer-based microchips under physiological conditions and enables the initial optimization of separation conditions in parallel to the chip development.
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| 10. |
- Porras Hernández, Ana María
(author)
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Micropatterning of hyaluronic acid hydrogels for in vitro models
- 2022
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Doctoral thesis (other academic/artistic)abstract
- The human body consist of a vast number of cells, and jointly, the cells, form tissues and organs. The cells interact and respond to their local microenvironment. The cellular microenvironment consists of a highly hydrated and compliant extracellular matrix, neighboring cells and circulating biochemical factors; and jointly, provide chemical and physical cues that regulate cell behaviour However, these cues are often not present in traditional in vitro models, where cells experience a stiff and unstructured environment. An approach to better mimic the in vivo microenvironment in vitro is to use hydrogels. Hydrogels are soft and highly hydrated polymers based on materials naturally found in the extracellular matrix of various tissues. Furthermore, these materials can be chemically functionalized to control the physical, chemical, and mechanical properties of the hydrogels. These functionalities can also be used to prepare micrometre sized cell adhesive regions, or micropatterns, on the hydrogel substrate. The micropatterns guide the cell shape and permit the study of the cell response to these changes in shape and function, which has been observed in e.g., endothelial cells from various origins. Taken all together, the aim of this work was to develop a hydrogel-based cell culture substrate that permits the control of the spatial adhesion of brain endothelial cells in order to study the morphological effects on these cells and contribute to the understanding of the function of brain endothelial cells in health and disease. This thesis demonstrates the functionalization of hyaluronic acid, a naturally occurring extracellular matrix polymer, to prepare photocrosslinkable hydrogels. Then, through photolithography, micropatterns of cell adhesive peptides were prepared on these hydrogels. Brain microvascular endothelial cells, a highly specialized type of endothelial cells, adhered to the micropatterns, and the effect on their alignment and cell chirality depending on the micropatterned sized was studied. Furthermore, changes in their alignment were also observed when exposed to different glucose concentration.
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