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Sökning: WFRF:(Wijngaart Wouter van der) > (2015-2019)

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1.
  • Ladhani, Laila, et al. (författare)
  • Sampling and detection of airborne influenza virus towards point-of-care applications
  • 2017
  • Ingår i: PLOS ONE. - : Plos One. - 1932-6203.
  • Tidskriftsartikel (refereegranskat)abstract
    • Airborne transmission of the influenza virus contributes significantly to the spread of this infectious pathogen, particularly over large distances when carried by aerosol droplets with long survival times. Efficient sampling of virus-loaded aerosol in combination with a low limit of detection of the collected virus could enable rapid and early detection of airborne influenza virus at the point-of-care setting. Here, we demonstrate a successful sampling and detection of airborne influenza virus using a system specifically developed for such applications. Our system consists of a custom-made electrostatic precipitation (ESP)-based bioaerosol sampler that is coupled with downstream quantitative polymerase chain reaction (qPCR) analysis. Aerosolized viruses are sampled directly into a miniaturized collector with liquid volume of 150 μL, which constitutes a simple and direct interface with subsequent biological assays. This approach reduces sample dilution by at least one order of magnitude when compared to other liquid-based aerosol bio-samplers. Performance of our ESP-based sampler was evaluated using influenza virus-loaded sub-micron aerosols generated from both cultured and clinical samples. Despite the miniaturized collection volume, we demonstrate a collection efficiency of at least 10% and sensitive detection of a minimum of 3721 RNA copies. Furthermore, we show that an improved extraction protocol can allow viral recovery of down to 303 RNA copies and a maximum sampler collection efficiency of 47%. A device with such a performance would reduce sampling times dramatically, from a few hours with current sampling methods down to a couple of minutes with our ESP-based bioaerosol sampler.
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2.
  • Lenk, Gabriel, et al. (författare)
  • Capillary driven and volume-metred blood-plasma separation
  • 2015
  • Ingår i: Proceedings 18 th IEEE Transducers. - : IEEE. - 9781479989553 ; , s. 335-338
  • Konferensbidrag (refereegranskat)abstract
    • Blood plasma samples are widely used in clinical analysis but easy-to-use sampling methods for defined volumes are lacking. We introduce the first capillary driven microfluidic device that separates a specific volume of plasma from a blood sample of unknown volume. The input to the device is a small amount of whole blood in the range of 30-60 μl which results in a 4 μl isolated plasma sample within 3 minutes, available for subsequent processing and/or analysis, as demonstrated by collecting the sample in a paper substrate.
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3.
  • Becker, Holger, et al. (författare)
  • Microfluidic system for the identification of bacterial pathogens causing urinary tract infections
  • 2015
  • Ingår i: Microfluidics, BioMEMS, and Medical Microsystems XIII. - : SPIE - International Society for Optical Engineering. - 9781628414103
  • Konferensbidrag (refereegranskat)abstract
    • Urinary tract infections (UTIs) are among the most common bacterial infections and pose a significant healthcare burden. The growing trend in antibiotic resistance makes it mandatory to develop diagnostic kits which allow not only the determination of a pathogen but also the antibiotic resistances. We have developed a microfluidic cartridge which takes a direct urine sample, extracts the DNA, performs an amplification using batch-PCR and flows the sample over a microarray which is printed into a microchannel for fluorescence detection. The cartridge is injection-molded out of COP and contains a set of two-component injection-molded rotary valves to switch between input and to isolate the PCR chamber during thermocycling. The hybridization probes were spotted directly onto a functionalized section of the outlet microchannel. We have been able to successfully perform PCR of E. coli in urine in this chip and perform a fluorescence detection of PCR products. An upgraded design of the cartridge contains the buffers and reagents in blisters stored on the chip.
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4.
  • Brugger, J., et al. (författare)
  • Letter from the chairs
  • 2015
  • Ingår i: IEEE International Conference on Micro Electro Mechanical Systems. - : IEEE conference proceedings. - 1084-6999. ; 2015-February:February
  • Tidskriftsartikel (refereegranskat)
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5.
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6.
  • Decrop, Deborah, et al. (författare)
  • Single-step imprinting of femtoliter microwell arrays allows digital bioassays with attomolar limit of detection
  • 2017
  • Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:12, s. 10418-10426
  • Tidskriftsartikel (refereegranskat)abstract
    • Bead-based microwell array technology is growing as an ultrasensitive target detection tool. However, dissemination of the technology and its commercial use are hampered by current fabrication methods for hydrophilic-in-hydrophobic microwell arrays, which are either expensive or labour-intensive to manufacture, or which results in low bead seeding efficiencies. In this paper, we present a novel single-step manufacturing method for imprinting cheap and disposable hydrophilic-in-hydrophobic microwell arrays suitable for single-molecule detection. Single-step imprinting of hydrophilic-in-hydrophobic microwell arrays is made possible using an innovative surface energy replication approach by means of a hydrophobic thiol-ene polymer formulation. In this polymer, hydrophobic-moiety-containing monomers self-assemble against the hydrophobic surface of the imprinting stamp, which results in a hydrophobic replica surface after polymerization. After removing the stamp, hydrophilic wells are obtained with the well bottoms consisting of glass substrate. We demonstrate that the hydrophilic-in-hydrophobic imprinted microwell arrays enable successful and efficient self-assembly of individual water droplets and seeding of magnetic beads with loading efficiencies up to 96%. We also demonstrate the suitability of the microwell arrays for the isolation and detection of single-molecules achieving a limit of detection of 17.4 aM when performing a streptavidin-biotin binding assay. The ease of manufacturing demonstrated here is expected to allow translation of digital microwell array technology towards diagnostic applications.
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7.
  • Decrop, Deborah, et al. (författare)
  • Single-step manufacturing of femtoliter microwell arrays in a novel surface energy mimicking polymer
  • 2015
  • Ingår i: 18th International Conference on Solid-State Sensors, Actuators and Microsystems (IEEE TRANSDUCER 2015). - : IEEE.
  • Konferensbidrag (refereegranskat)abstract
    • We report a novel polymer material formulation and stamp-molding technique that enable rapid single-step manufacturing of hydrophilic-in-hydrophobic microwell arrays. We developed a modified thiol-ene-epoxy polymer (mOSTE+) formulation that mimics the surface energy of its mold during polymerization. The polymer inherits the surface energy from the mold through molecular self-assembly, in which functional monomers self-assemble at the interface between the liquid prepolymer and the mold surface. Combining this novel mOSTE+ material with a stamp-molding process leads to simultaneous surface energy mimicking and micro-structuring. This method was used to manufacture microwells with hydrophilic bottom and hydrophobic sidewall, depressed in a surrounding hydrophobic surface. The microwell arrays were successfully tested for the self-assembly of 62’000 femtoliter-droplets. Such femtoliter droplet arrays are useful for, e.g., digital ELISA and single cell/molecule analysis applications.
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8.
  • Guha, Arnab, et al. (författare)
  • Measurement of protein binding with vastly improved time resolution using a quartz crystal microbalance driven at a fixed frequency
  • 2017
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Quartz crystal microbalance (QCM) is commonly used to study biomolecular binding by measuring shifts in resonance frequency of a quartz-crystal-oscillator. However, the currently used methods like impedance analysis or QCM-D, which require repeated sweeps or ringing, are limited in time resolution (~1 second) due to the need for averaging. This restricts our ability to study transient biomolecular processes, which occur in sub-millisecond time scale. A novel technique has been reported here that allows quantification of resonance frequency of a quartz-crystal-oscillator with significantly improved time resolution by driving and measuring continuously at a constant frequency within the resonance bandwidth. Method: The reactive component of the experimentally obtained impedance is utilized for the estimation of resonance frequency from the Butterworth Van-dyke (BVD) model of a quartz-crystal-oscillator, assuming that changes in motional inductance and capacitance around resonance are negligible. Triplicate sets of experiments involving the binding of streptavidin with a biotin functionalized 14.3 MHz quartz oscillator surface were performed. Intermittent frequency sweeps and fixed frequency drives, both of 0.1 second duration and around 14.3 MHz, were taken at intervals of 2 minutes under the flow of phosphate-buffer-saline (PBS buffer) before and after injection of streptavidin. Results: The average shift in resonance frequency from the baseline (measurements before streptavidin injection) due to streptavidin-biotin binding, calculated from the fixed frequency drive or FFD (148 Hz) was within 1% of that estimated from the frequency sweep method by fitting the experimentally recorded impedance employing the BVD model (149 Hz). Discussion: The agreement of the FFD with conventional frequency sweep method suggests that protein binding can be quantified with reasonable accuracy from each impedance data point, which with our set-up is recorded at 30 kHz sampling rate. This gives a time resolution of 0.03 millisecond, which is about 4 orders of magnitude improvement over the state-of-the-art.
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9.
  • Guha, Arnab, et al. (författare)
  • Simple and ultrafast resonance frequency and dissipation shift measurements using a fixed frequency drive
  • 2018
  • Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 281, s. 960-970
  • Tidskriftsartikel (refereegranskat)abstract
    • A new method for determination of resonance frequency and dissipation of a mechanical oscillator is presented. Analytical expressions derived using the Butterworth-Van Dyke equivalent electrical circuit allow the determination of resonance frequency and dissipation directly from each impedance datapoint acquired at a fixed amplitude and frequency of drive, with no need for numerical fitting or measurement dead time unlike the conventional impedance or ring-down analysis methods. This enables an ultrahigh time resolution and superior noise performance with relatively simple instrumentation. Quantitative validations were carried out successfully against the impedance analysis method for inertial and viscous loading experiments on a 14.3 MHz quartz crystal resonator (QCR). Resonance frequency shifts associated with the transient processes of quick needle touches on a thiol self-assembled-monolayer functionalised QCR in liquid were measured with a time resolution of 112 μs, which is nearly two orders of magnitude better than the fastest reported quartz crystal microbalance. This simple and fast fixed frequency drive (FFD) based method for determination of resonance frequency and dissipation is potentially more easily multiplexable and implementable on a single silicon chip delivering economies of scale.
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10.
  • Guo, Maoxiang, et al. (författare)
  • Cross-membrane electrical detection of DNA
  • 2017
  • Ingår i: Proceedings 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017. - : The Chemical and Biological Microsystems Society (CBMS).
  • Konferensbidrag (refereegranskat)abstract
    • We introduce out-of-plane metallic nanowire formation on DNA templates, which are stretched through a porous membrane by applying a receding meniscus interface. We demonstrate the direct electrical detection of DNA using these gold nanowire bridges between the membrane’s opposite surfaces. Such a simple electrical readout can be extended for biosensor applications, thanks to the high specificity and multiplexing offered by Rolling Circle Amplification (RCA).
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11.
  • Guo, Maoxiang (författare)
  • Digital Electrical DNA Sensing
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Molecule detection is a workhorse in life sciences and medicine, for example in cancer diagnosis and virus and bacterial detection. DNA analysis can provide vital information about the state of a host organism and its medical and health condition. A central challenge in DNA sensing lays in obtaining the following key detection characteristics in a single device: low limit of detection, small sample volume, high specificity, quantification, rapid time-to-result at a low cost.Here we investigate whether direct electrical DNA sensing in a miniaturized detector can enable such performance. The detector consists of a gold-coated thin porous membrane, functionalized with oligonucleotides receptors, that is sandwiched between two off-stoichiometric thiol-ene-epoxy layers. The device works as follows. First, target DNA in the sample is specifically recognized by padlock probe hybridization and ligation. Second, the target-receptor circular molecules are amplified by rolling circle amplification (RCA), generating long ssDNA concatemers (RCP). Third, the RCPs are stretched through the membrane pores. Fourth, DNA metallization was used to form the gold nanowires bridging both sides of membrane pores after gold enhancement, which results in a conductive path that is measured with a simple resistance measurement. The thesis describes the engineering technology that enables low LoD detection of ssDNA using a digital measurement and details the development and optimization of the detector fabrication and operation, including structural design, materials, and microfluidic operation. We demonstrated a detector with sub-aM LoD, high specificity and simple operation in a miniaturized and uncomplicated format. Furthermore, the thesis studies the long-term liquid storage in nL scale well arrays fabricated in off-stoichiometric thiol-ene (OSTE). We demonstrated liquid storage with < 10 % loss of stored PBS buffer for 33 days and the on-demand electrically controlled liquid release.The thesis presents the potential of a combination DNA detector with the method of liquid storage. Combining the on-chip liquid storage and DNA detection methods could provide a powerful alternative to conventional bio-detectors used in molecular diagnostics, and improved performance in multiplexed point-of-care sensing of (ultra-low abundant) biomolecules.
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12.
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13.
  • Guo, Maoxiang, et al. (författare)
  • Efficient DNA-assisted synthesis of trans-membrane gold nanowires
  • 2018
  • Ingår i: microsystems and nanoengineering. - : Springer Science and Business Media LLC. - 2055-7434. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Whereas electric circuits and surface-based (bio) chemical sensors are mostly constructed in-plane due to ease of manufacturing, 3D microscale and nanoscale structures allow denser integration of electronic components and improved mass transport of the analyte to (bio) chemical sensor surfaces. This work reports the first out-of-plane metallic nanowire formation based on stretching of DNA through a porous membrane. We use rolling circle amplification (RCA) to generate long single-stranded DNA concatemers with one end anchored to the surface. The DNA strands are stretched through the pores in the membrane during liquid removal by forced convection. Because the liquid-air interface movement across the membrane occurs in every pore, DNA stretching across the membrane is highly efficient. The stretched DNA molecules are transformed into trans-membrane gold nanowires through gold nanoparticle hybridization and gold enhancement chemistry. A 50 fM oligonucleotide concentration, a value two orders of magnitude lower than previously reported for flat surface-based nanowire formation, was sufficient for nanowire formation. We observed nanowires in up to 2.7% of the membrane pores, leading to an across-membrane electrical conductivity reduction from open circuit to <20 Omega. The simple electrical read-out offers a high signal-to-noise ratio and can also be extended for use as a biosensor due to the high specificity and scope for multiplexing offered by RCA.
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14.
  • Guo, Maoxiang, et al. (författare)
  • LONG-TERM STORAGE OF NANOLITRE AND PICOLITRE LIQUID VOLUMES IN POLYMER MICROFLUIDIC DEVICES
  • 2015
  • Ingår i: the 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences (Micro TAS). - : The Chemical and Biological Microsystems Society. - 9780979806483 ; , s. 1386-1388
  • Konferensbidrag (refereegranskat)abstract
    • We introduce uncomplicated nanolitre (23 nL) and picolitre (3.5 pL) liquid volume encapsulation in Off-Stoichiometry Thiol-Ene-Epoxy polymer (OSTEmerTM322) wells using spontaneous room- temperature bonding of gold films to thiol and thioether groups present on the surface of the polymer for leak free sealing. First, we show liquid encapsulation within nL, and pL polymer wells by utilizing 100 nm thin Au-film transfer-bonding onto intermediately cured, and micropatterned OSTEmerTM322. This approach yielded 3 magnitude orders smaller liquid volume encapsulation than previously reported. Secondly, we show that encapsulated liquid can be stored for >116 h. Finally, we demonstrate encapsulated liquid release by thermopneumatic bursting. We conclude that OSTEmerTM322 is excellent for metal-film sealant integration in polymer microfluidic devices. 
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15.
  • Guo, Weijin, 1989-, et al. (författare)
  • Capillary Pumping Independent Of Liquid Sample Viscosity
  • 2016
  • Ingår i: Langmuir. - Washington, DC 20036 : American Chemical Society (ACS). - 0743-7463 .- 1520-5827.
  • Tidskriftsartikel (refereegranskat)abstract
    • Capillary flow is a dominating liquid transport phenomenon on the micro- and nanoscale. As described at the beginning of the 20th century, the flow rate during imbibition of a horizontal capillary tube follows the Washburn equation, i.e. decreases over time and depends on the viscosity of the sample. This poses a problem for capillary driven systems that rely on a predictable flow rate and where the liquid viscosity is not precisely known. Here we introduce and successfully experimentally verify the first compact capillary pump design with a flow rate constant in time and independent of the liquid viscosity that can operate over an extended period of time. We also present a detailed theoretical model for gravitation independent capillary filling, which predicts the novel pump performance to within measurement error margins, and in which we, for the first time, explicitly identify gas inertia dominated flow as a fourth distinct flow regime in capillary pumping. These results are of potential interest for a multitude of applications and we expect our results to find most immediate applications within lab-on-a-chip systems and diagnostic devices.
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16.
  • Guo, Weijin, 1989-, et al. (författare)
  • Capillary pumping independent of the liquid surface energy and viscosity
  • 2018
  • Ingår i: Microsystems & Nanoengineering. - : Springer Nature. - 2055-7434. ; 4:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Capillary pumping is an attractive means of liquid actuation because it is a passive mechanism, i.e., it does not rely on an external energy supply during operation. The capillary flow rate generally depends on the liquid sample viscosity and surface energy. This poses a problem for capillary-driven systems that rely on a predictable flow rate and for which the sample viscosity or surface energy are not precisely known. Here, we introduce the capillary pumping of sample liquids with a flow rate that is constant in time and independent of the sample viscosity and sample surface energy. These features are enabled by a design in which a well-characterized pump liquid is capillarily imbibed into the downstream section of the pump and thereby pulls the unknown sample liquid into the upstream pump section. The downstream pump geometry is designed to exert a Laplace pressure and fluidic resistance that are substantially larger than those exerted by the upstream pump geometry on the sample liquid. Hence, the influence of the unknown sample liquid on the flow rate is negligible. We experimentally tested pumps of the new design with a variety of sample liquids, including water, different samples of whole blood, different samples of urine, isopropanol, mineral oil, and glycerol. The capillary filling speeds of these liquids vary by more than a factor 1000 when imbibed to a standard constant cross-section glass capillary. In our new pump design, 20 filling tests involving these liquid samples with vastly different properties resulted in a constant volumetric flow rate in the range of 20.96–24.76 μL/min. We expect this novel capillary design to have immediate applications in lab-on-a-chip systems and diagnostic devices.
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17.
  • Guo, Weijin, 1989-, et al. (författare)
  • Capillary pumping with a constant flow rate independent of the liquid sample viscosity and surface energy
  • 2017
  • Ingår i: Proceeding of 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS). - : IEEE. - 9781509050789
  • Konferensbidrag (refereegranskat)abstract
    • We introduce and experimentally verify a capillary pump design that, for the first time, enables autonomous pumping of sample liquid with a flow rate constant in time and independent of the sample viscosity and sample surface energy. These results are of interest for applications that rely on a predictable flow rate and where the sample fluid viscosity or surface energy are not precisely known, e.g. in capillary driven diagnostic lateral flow biosensors for urine or blood sample, where large variations exist in both viscosity and surface energy between different patient samples.
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18.
  • Guo, Weijin, et al. (författare)
  • Formation of a thin-walled Spider Silk Tube on a Micromachined Scaffold
  • 2018
  • Ingår i: Proceeding of 2018 IEEE 31st International Conference on Micro Electro Mechanical Systems (MEMS). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538647820 ; , s. 83-85
  • Konferensbidrag (refereegranskat)abstract
    • This paper reports on the first formation of a thin bio-functionalized spider silk tube, supported by an internal micromachined scaffold, in which both the inside and outside of the tube wall are freely accessible. The silk tube could potentially be used as an artificial blood vessel in an in vitro tissue scaffold, where endothelial cells and tissue cells can grow on both sides of the silk tube.
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19.
  • Guo, Weijin, et al. (författare)
  • Synthetic microfluidic paper with superior fluorescent signal readout
  • 2019
  • Ingår i: Proceedings of The 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9781733419000 ; , s. 1056-1057
  • Konferensbidrag (refereegranskat)abstract
    • This work is the first report on the use of synthetic microfluidic paper for lateral flow immunoassays. We grafted test lines of biotin on the synthetic paper using the thiol-yne “click” reaction. We captured fluorescently labeled streptavidin in a lateral flow fashion. Our two main findings are that, compared to other polymer lateral flow substrates with similar surface area, the synthetic microfluidic paper geometry results in 1) a stronger and more stable fluorescent signal per capture area, and 2) a sensitivity ~7 times higher.
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20.
  • Guo, Weijin, 1989-, et al. (författare)
  • Viscosity Independent Paper Microfluidic Imbibition
  • 2016
  • Ingår i: Proceedings of The 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016. - : MicroTAS. - 9780979806490 ; , s. 13-14
  • Konferensbidrag (refereegranskat)abstract
    • This work introduces capillary flow in paper microfluidics that features a flow rate Q that is constant in time, t, and independent of the viscosity of liquid sample, μ liquid: Q≠f(t, μ liquid). Compared to conventional paper microfluidics, we enclose the paper in solid walls and add a long and narrow air vent as outlet of the capillary pump, such that the flow rate is dominated by the downstream air resistance. Therefore, the flow rate depends on the viscosity of air rather than that of liquid. This significantly decreases the dependency of lateral flow biosensors on variations of sample fluid.
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21.
  • Gustafsson, Linnea, et al. (författare)
  • Structuring of Functional Spider Silk Wires, Coatings, and Sheets by Self-Assembly on Superhydrophobic Pillar Surfaces
  • 2018
  • Ingår i: Advanced Materials. - : John Wiley & Sons. - 0935-9648 .- 1521-4095. ; 30:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Spider silk has recently become a material of high interest for a large number of biomedical applications. Previous work on structuring of silk has resulted in particles (0D), fibers (1D), films (2D), and foams, gels, capsules, or microspheres (3D). However, the manufacturing process of these structures is complex and involves posttreatment of chemicals unsuitable for biological applications. In this work, the self-assembly of recombinant spider silk on micropatterned superhydrophobic surfaces is studied. For the first time, structuring of recombinant spider silk is achieved using superhydrophobic surfaces under conditions that retain the bioactivity of the functionalized silk. By tuning the superhydrophobic surface geometry and the silk solution handling parameters, this approach allows controlled generation of silk coatings, nanowires, and sheets. The underlying mechanisms and governing parameters are discussed. It is believed that the results of this work pave the way for fabrication of silk formations for applications including vehicles for drug delivery, optical sensing, antimicrobial coatings, and cell culture scaffolds.
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22.
  • Gylfason, Kristinn B., 1978-, et al. (författare)
  • Integration of polymer based microfluidics with silicon photonics for biosensing applications
  • 2015
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • We present a novel integration method for packaging silicon photonic sensors with polymer microfluidics, designed to be suitable for wafer-level production. The method addresses the previously unmet manufacturing challenges of matching the microfluidic footprint area to that of the photonics, and of robust bonding of microfluidic layers to biofunctionalized surfaces. We demonstrate the fabrication, in a single step, of a microfluidic layer in the recently introduced OSTE polymer, and the subsequent unassisted dry bonding of the microfluidic layer to a grating coupled silicon photonic ring resonator sensor chip. The microfluidic layer features photopatterned through holes (vias) for optical fiber probing and fluid connections, as well as molded microchannels and tube connectors, and is manufactured and subsequently bonded to a silicon sensor chip in less than 10 minutes. Combining this new microfluidic packaging method with photonic waveguide surface gratings for light couplin g allows matching the size scale of microfluidics to that of current silicon photonic biosensors.
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23.
  • Hansson, Jonas, 1983- (författare)
  • From Lab to Chip – and back : Polymer microfluidic systems for sample handling in point-of-care diagnostics
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis contributes to the development of Lab-on-a-Chip systems that enables reliable, rapid medical diagnostics at the point-of-care. These contributions are focused on microfluidic Lab-on-a-Chip systems for sepsis diagnosis, autonomous sample-to-answer tests, and dried blood spot sampling.Sepsis is a serious condition with high mortality and high costs for society and healthcare. To facilitate rapid and effective antibiotic treatment, improved sepsis diagnostics is needed. Diagnosis of sepsis requires the processing of relatively large blood volumes, creating a need for novel and effective techniques for the handling of large volume flows and pressures on chip. Components, materials, and manufacturing methods for pneumatically driven Lab-on-a-Chip systems have therefore been developed in this thesis. Microvalves, an essential component in many Lab-on-a-Chip systems have been the focus on several of the advances: a novel elastomeric material (Rubbery Off-Stoichiometric-Thiol-Ene-Epoxy) with low gas and liquid permeability; the first leak-tight vertical membrane microvalves, allowing large channel cross-sections for high volumetric flow throughput; and novel PDMS manufacturing methods enabling their realization. Additionally, two of the new components developed in this thesis focus on separation of bacteria from blood cells based on differences in particle size, and cell wall composition: inertial microfluidic removal of large particles in multiple parallel microchannels with low aspect ratio; and selective lysis of blood cells while keeping bacteria intact. How these components, materials and methods could be used together to achieve faster sepsis diagnostics is also discussed.Lab-on-a-Chip tests can not only be used for sepsis, but have implications in many point-of-care tests. Disposable and completely autonomous sampleto- answer tests, like pregnancy tests, are capillary driven. Applying such tests in more demanding applications has traditionally been limited by poor material properties of the paper-based products used. A new porous material, called “Synthetic Microfluidic Paper”, has been developed in this thesis. The Synthetic Microfluidic Paper features well-defined geometries consisting of slanted interlocked micropillars. The material is transparent, has a large surface area, large porous fraction, and results in low variability in capillary flowrates. The fact that Synthetic Microfluidic Paper can be produced with multiple pore sizes in the same sheet enables novel concepts for self-aligned spotting of liquids and well-controlled positioning of functional microbeads.Diagnostic testing can also be achieved by collecting the sample at the point-of-care while performing the analysis elsewhere. Easy collection of finger-prick blood in paper can be performed by a method called dried blood spots. This thesis investigates how the process of drying affects the homogeneity of dried blood spots, which can explain part of the variability that has been measured in the subsequent analysis. To reduce this variability, a microfluidic sampling chip has been developed in this thesis. The chip, which is capillary driven, autonomously collects a specific volume of plasma from a drop of blood, and dry-stores it in paper. After sampling, the chip can be mailed back to a central lab for analysis.
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24.
  • Hansson, Jonas, et al. (författare)
  • Leak-tight vertical membrane microvalves
  • 2016
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 16:8, s. 1439-1446
  • Tidskriftsartikel (refereegranskat)abstract
    • Pneumatic microvalves are fundamental control components in a large range of microfluidic applications. Their key performance parameters are small size, i.e. occupying a minimum of microfluidic real estate, low flow resistance in the open state, and leak-tight closing at limited control pressures. In this work we present the successful design, realization and evaluation of the first leak-tight, vertical membrane, pneumatic microvalves. The realization of the vertical membrane microvalves is enabled by a novel dual-sided molding method for microstructuring monolithic 3D microfluidic networks in PDMS in a single step, eliminating the need for layer-to-layer alignment during bonding. We demonstrate minimum lateral device features down to 20-30 mu m in size, and vertical via density of similar to 30000 per cm(2), which provides significant gains in chip real estate compared to previously reported PDMS manufacturing methods. In contrast to horizontal membrane microvalves, there are no manufacturing restrictions on the cross-sectional geometry of the flow channel of the vertical membrane microvalves. This allows tuning the design towards lower closing pressure or lower open state flow resistance compared to those of horizontal membrane microvalves.
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25.
  • Hansson, Jonas, et al. (författare)
  • Synthetic microfluidic paper
  • 2015
  • Ingår i: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - : IEEE conference proceedings. ; , s. 10-13
  • Konferensbidrag (refereegranskat)abstract
    • We introduce a polymer synthetic microfluidic paper for lateral flow devices. The aim is to combine the high surface area of paper, or nitrocellulose, with the repeatability, controlled structure, and transparency of polymer micropillars. Our synthetic paper consists of a dense, high aspect ratio array of transparent pillars that are slanted and mechanically interlocked. We describe the manufacturing using multidirectional UV lithography and demonstrate successful capillary pumping of whole blood.
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26.
  • Hansson, Jonas, et al. (författare)
  • Synthetic microfluidic paper allows controlled receptor positioning and improved readout signal intensity in lateral flow assays
  • 2015
  • Ingår i: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. - 9780979806483 ; , s. 284-286
  • Konferensbidrag (refereegranskat)abstract
    • Synthetic Microfluidic Paper consists of slanted and interlocked polymer micropillars and can be used as a porous substrate in microfluidics and lateral flow assays. We here demonstrate single step manufacturing of multiple Synthetic Microfluidic Paper densities in the same device, and passive alignment of liquid spots in denser substrate regions, regardless of spotting position, allowing increased control of receptor positioning for lateral flow assays. We further demonstrate that the transparency of Synthetic Microfluidic Paper allows increasing readout signal intensity with increasing substrate thickness, to a value 3 times larger compared to nitrocellulose substrates.
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27.
  • Hansson, Jonas, 1983-, et al. (författare)
  • Synthetic paper
  • 2017
  • Patent (populärvet., debatt m.m.)abstract
    • A synthetic paper is manufactured with a method comprising the steps of: a) providing at least two types of pho to-polymerizable monomers, b) exposing the volume to a three-dimensional light pattern to induce a polymerization reaction, and c) removing uncured monomer to create an open microstructure. The volume comprises at least one monomer comprising at least two thiol groups and at least one monomer comprising at least two carbon-carbon double bonds, where the ratio (r1) between the number of thiol groups and the number of carbon-carbon double bonds fulfils one of: 0.5≦r1≦0.9 and 1.1≦r1≦2. One advantage is that off stoichiometry creates an edge effect giving better defined boundaries between exposed and unexposed parts in the volume and giving a possibility to create thinner micro pillars. Another advantage is that it is easy to bind molecules to the surface to obtain desired surface properties.
  •  
28.
  • Hansson, Jonas, et al. (författare)
  • Vertical membrane microvalves in PDMS
  • 2015
  • Ingår i: 2015 28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - : IEEE. ; , s. 563-565
  • Konferensbidrag (refereegranskat)abstract
    • We present the design, realization and evaluation of the first leak-tight vertical membrane pneumatic microvalve. The design freedom in the vertical valve configuration allows for a flow throughput per footprint area that is increased two orders of magnitude compared to horizontal membrane microvalves.
  •  
29.
  • Hedhammar, My, Professor, 1975-, et al. (författare)
  • Structuring of surface-active macromolecules
  • 2019
  • Patent (populärvet., debatt m.m.)abstract
    • A method for manufacturing shaped polymers of surface-active macromolecules, in particular silk, is provided. The method is comprising the steps of: • a) depositing an aqueous solution of the surface-active macromolecules on a surface, wherein the aqueous solution of the surface-active macromolecules is deposited in the form of a droplet, and wherein the surface is a hydrophobic micropatterned surface adapted to prevent the aqueous solution from penetrating into the pattern and to receive the droplet of the aqueous solution of the surface-active macromolecules and retain its droplet state; and • b) forming shaped polymers of the surface-active macromolecules on the surface.    
  •  
30.
  • Imani Jajarmi, Ramin, 1987-, et al. (författare)
  • The Influence of Air Flow Velocity and Particle Size on the Collection Efficiency of Passive Electrostatic Aerosol Samplers
  • 2019
  • Ingår i: Aerosol and Air Quality Research. - : Taiwan Association for Aerosol Research. - 1680-8584 .- 2071-1409. ; 19:2, s. 192-203
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrostatic sampling is a promising method for the collection of bioaerosol particles. Although the underlying physics responsible for particle collection are well understood, the collection efficiency of simple passive electrostatic samplers is difficult to predict. Under these conditions, the collection efficiency becomes very sensitive to ambient air current and particle size, especially for submicron particles relevant for airborne virus transmission. In this paper, we compare two electrostatic aerosol sampler designs, a commercial product consisting of a flat collector plate located in the same plane as the charging needles and an axisymmetric design sampling directly to a liquid droplet. The aerosol particle collection efficiency of the samplers is investigated for particle size ranging from 0.25 to 2 µm while the air flow velocity surrounding the samplers is varied from 0.3 to 1 m s–1. For the planar design, at all ambient flow velocities, the submicron fraction of the particles captured originates in streamlines up to a maximum of 75 mm above the surface of the device collector, which greatly limits the volume of air being effectively sampled. The axisymmetric design features a non-monotonic capture efficiency as a function of particle size, with a minimum between 0.4 and 0.8 µm. The flow field in the inter-electrode region, captured using particle image velocimetry (PIV) reveals the presence of strong recirculation zones that can be responsible for the increased collection efficiency for very small particles.
  •  
31.
  • Iseri, Emre, et al. (författare)
  • Detection of E.coli in a digital assay
  • 2018
  • Ingår i: 2018 IEEE Micro Electro Mechanical Systems (MEMS). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538647820 ; , s. 301-303
  • Konferensbidrag (refereegranskat)abstract
    • In this paper, we demonstrate the dipstick-based digitisation and detection of bacterial sample of concentration down to 103 CFU/ml. The significance of this work is that we are able to detect concentrations of bacteria relevant for urinary tract infection (UTI) with minimal handling time and without the need for complicated external equipment.
  •  
32.
  • Iseri, Emre, et al. (författare)
  • Tuneable Microparticle Filters
  • 2019
  • Ingår i: 2019 IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS). - : IEEE. ; , s. 290-291
  • Konferensbidrag (refereegranskat)abstract
    • We introduce microparticle filters with temperature tuneable size cut-off and surface energy. At room temperature, the filter cut-off is 164 ±23 μm, and the filter is water-absorbing/oil-repelling (hydrophilic). At 50 °C, the filter cut-off is 695±31 μm, and the filter is oil-absorbing/water-repelling (hydrophobic).
  •  
33.
  • Jonas, Hansson, 1983-, et al. (författare)
  • Synthetic microfluidic paper: high surface area and high porosity polymer micropillar arrays
  • 2016
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 16:2, s. 298-304
  • Tidskriftsartikel (refereegranskat)abstract
    • We introduce Synthetic Microfluidic Paper, a novel porous material for microfluidic applications that consists of an OSTE polymer that is photostructured in a well-controlled geometry of slanted and interlocked micropillars. We demonstrate the distinct benefits of Synthetic Microfluidic Paper over other porous microfluidic materials, such as nitrocellulose, traditional paper and straight micropillar arrays: in contrast to straight micropillar arrays, the geometry of Synthetic Microfluidic Paper was miniaturized without suffering capillary collapse during manufacturing and fluidic operation, resulting in a six-fold increased internal surface area and a three-fold increased porous fraction. Compared to commercial nitrocellulose materials for capillary assays, Synthetic Microfluidic Paper shows a wider range of capillary pumping speed and four times lower device-to-device variation. Compared to the surfaces of the other porous microfluidic materials that are modified by adsorption, Synthetic Microfluidic Paper contains free thiol groups and has been shown to be suitable for covalent surface chemistry, demonstrated here for increasing the material hydrophilicity. These results illustrate the potential of Synthetic Microfluidic Paper as a porous microfluidic material with improved performance characteristics, especially for bioassay applications such as diagnostic tests.
  •  
34.
  • Karlsson, J. Mikael, et al. (författare)
  • Off-Stoichiometry Improves Photostructuring of Thiol-Enes Through Diffusion-Induced Monomer Depletion
  • 2016
  • Ingår i: Microsystems and Nanoengineering. - : Nature Publishing Group. - 2055-7434. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Thiol-enes are a group of alternating copolymers with highly ordered networks used in a wide range of applications. Here, “click” chemistry photostructuring in off-stoichiometric thiol-enes is shown to induce microscale polymeric compositional gradients due to species diffusion between non-illuminated and illuminated regions, creating two narrow zones with distinct composition on either side of the photomask feature boundary: a densely cross-linked zone in the illuminated region and a zone with an unpolymerized highly off-stoichiometric monomer composition in the non-illuminated region. By the use of confocal Raman microscopy, it is here explained how species diffusion causes such intricate compositional gradients in the polymer, and how off-stoichiometry results in improved image transfer accuracy in thiol-ene photostructuring. Furthermore, increasing the functional group off-stoichiometry and decreasing photomask feature size is shown to amplify the induced gradients, which potentially leads to a new methodology for microstructuring.
  •  
35.
  • Ladhani, Laila, et al. (författare)
  • A 3D microfluidic cage collector for airborne particles
  • 2015
  • Ingår i: The 19th International Conference on Miniaturised Systems for Chemistry and Life Sciences, MicroTAS. - : Royal Society of Chemistry. - 9780979806483 ; , s. 79-81
  • Konferensbidrag (refereegranskat)abstract
    • We designed, manufactured, and integrated the first 3D microfluidic collector for capturing airborne particles directly into liquid; using an integrated electrostatic precipitator (ESP) sampler, designed for breath diagnostic purposes. The novel collector increases the sampler’s air-to-liquid capture efficiency by 35 times, when compared with previous 2D collectors. 
  •  
36.
  • Ladhani, Laila (författare)
  • An electrostatic sampling device for point-of-care detection of bioaerosols
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Bioaerosols are not only a significant factor of air quality but contribute greatly to the spread of infectious diseases, specifically through expired pathogen-laden aerosols. Clear examples of airborne transmission include: the recent influenza pandemic of 2009, the ongoing tuberculosis epidemic, and yearly norovirus out- breaks, which affect millions of people worldwide and pose serious threats to public healthcare systems. Given these acute concerns and the critical lack of knowledge of the field, it is important to develop methods for sampling and detecting these air- borne pathogens. Specifically, detection at the point-of-care can play an important role in improving the outcome of patient care by providing rapid and convenient diagnostics.Electrostatic precipitation has emerged as a promising sampling tool for bio- aerosols, which together with a rapid analysis technique, can provide a powerful and integrated approach to pathogen detection or disease diagnosis at the point- of-care. Moreover, such a sampling-detection scheme could be a potentialy non- invasive breath sampling tool for diagnosis of respiratory infectious diseases.This thesis presents a sampling device based on electrostatic precipitation, for capture of bioaerosols, and designed for use at point-of-care settings. A multi-point- to-plane electrode configuration allows charging of aerosol particles and direct air- to-liquid capture within a miniaturized volume with potentential for concatenation with on-site detection methods. Performance of the device was evaluated, using non-biological aerosols, for geometric (inter-electrode distance), electrical (inter- electrode potential and corona current), and aerosol parameters (particle size and gas velocity). Moreover, four different collector designs were investigated for im- proved collection efficiency and other features suitable for point-of-care settings (e.g. easy sample extraction and minimized volume).The device was then validated, using bioaerosols, both in vitro and in vivo. In vitro validation was performed by capturing aerosolized influenza virus and analyz- ing the device collection efficiency. Lastly, prototype devices, designed for point- of-care, were validated in vivo with patients at the clinical setting. A pilot study was performed to capture exhaled pathogens from infected patients, with success- ful capture of exhaled bacteria.
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37.
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38.
  • Lobov, Gleb, et al. (författare)
  • Electro-optical effects of high aspect ratio P3HT nanofibers colloid in polymer micro-fluid cells
  • 2017
  • Ingår i: Optics Letters. - : OSA Publishing. - 0146-9592 .- 1539-4794. ; 42:11, s. 2157-2160
  • Tidskriftsartikel (refereegranskat)abstract
    • This Letter reports the electro-optical (EO) effect of Poly(3-hexylthiophene-2,5-diyl) (P3HT) nanofibers colloid in a polymer micro-fluidic EO cell. P3HT nanofibers are high aspect ratio semiconducting nanostructures, and can be collectively aligned by an external alternating electric field. Optical transmission modulated by the electric field is a manifestation of the electro-optical effect due to high inner crystallinity of P3HT nanofibers. According to our results, the degree of alignment reaches a maximum at 0.6 V/μm of electric field strength, implying a big polarizability value due to geometry and electrical properties of P3HT nanofibers. We believe that one-dimensional crystalline organic nanostructures have a large potential in EO devices due to their significant anisotropy, wide variety of properties, low actuation voltages, and opportunity to be tailored via adjustment of the fabrication process.
  •  
39.
  • Löhr, J. -M, et al. (författare)
  • Nanoparticles for cancer therapy
  • 2017
  • Ingår i: Läkartidningen. - : Swedish Medical Association. - 0023-7205 .- 1652-7518. ; 114:27-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history, there is a huge gap between the exciting experimental possibilities and data and clinical studies making use of it. Of the cell-containing nanoparticles, only one formulation using gene-directed enzyme prodrug therapy (GDEPT) with CYP2B1 and ifosfamide was used in early clinical studies. Of the cellfree nanoparticles, some drug-releasing (doxorubicin) ones are in clinical use for trans-arterial chemoembolization (TACE) in liver tumors and metastasis. Using liposomes, both paclitaxel and irinotecan have been used in pancreatic cancer as the model indication. Nanoparticle-albumin-bound paclitaxel (NAB-paclitaxel) has also been developed and is now registered as a drug for first-line therapy of pancreatic cancer, as is the liposomal irinotecan. The novel nanoparticle formulations carry a big promise for even better performance, both in diagnosis and therapy; however, few of these has entered the clinic as of today.
  •  
40.
  • Löhr, M., et al. (författare)
  • Nanotekniken kan revolutionera behandlingen av cancer - Ger nya möjligheter att målstyra läkemedel, men flera stora utmaningar återstår att tackla
  • 2017
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 114, s. 27-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticles for cancer therapy Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history, there is a huge gap between the exciting experimental possibilities and data and clinical studies making use of it. Of the cell-containing nanoparticles, only one formulation using gene-directed enzyme prodrug therapy (GDEPT) with CYP2B1 and ifosfamide was used in early clinical studies. Of the cell-free nanoparticles, some drug-releasing (doxorubicin) ones are in clinical use for trans-arterial chemo-embolization (TACE) in liver tumors and metastasis. Using liposomes, both paclitaxel and irinotecan have been used in pancreatic cancer as the model indication. Nanoparticle-albumin-bound paclitaxel (NAB-paclitaxel) has also been developed and is now registered as a drug for first-line therapy of pancreatic cancer, as is the liposomal irinotecan. The novel nanoparticle formulations carry a big promise for even better performance, both in diagnosis and therapy; however, few of these has entered the clinic as of today.
  •  
41.
  • Marinins, Aleksandrs, et al. (författare)
  • Light Converting Polymer/Si Nanocrystal Composites with Stable 60-70% Quantum Efficiency and their Glass Laminates
  • 2017
  • Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:36, s. 30267-30272
  • Tidskriftsartikel (refereegranskat)abstract
    • Thiol-ene polymer/Si nanocrystal bulk hybrids were synthesized from alkyl-passivated Si nanocrystal (Si NC) toluene solutions. Radicals in the polymer provided a co-passivation of “dark” Si NCs, making them optically active and leading to a substantial ensemble quantum yield increase. Optical stability over several months was confirmed. The presented materials exhibit the highest photoluminescence quantum yield (~65%) of any solid-state Si NC hybrid reported to date. The broad tunability of thiol-ene polymer reactivity provides facile glass integration, as demonstrated by a laminated structure. This, together with extremely fast polymerization, makes the demonstrated hybrid material a promising candidate for light converting applications.
  •  
42.
  • Pardon, Gaspard, 1983-, et al. (författare)
  • Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface
  • 2015
  • Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 212, s. 344-352
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, the development of a point-of-care (PoC) system to capture aerosol from litres of air directly onto a microfluidic lab-on-chip for subsequent analysis is addressed. The system involves an electrostatic precipitator that uses corona charging and electrophoretic transport to capture aerosol droplets onto a microfluidic air-to-liquid interface for downstream analysis. A theoretical study of the governing geometric and operational parameters for optimal electrostatic precipitation is presented. The fabrication of an electrostatic precipitator prototype and its experimental validation using a laboratory-generated aerosolized dye is described. Collection efficiencies were comparable to those of a state-of-the-art Biosampler impinger, with the significant advantage of providing samples that are at least 10 times more concentrated. Finally, we discuss the potential of such a system for breath-based diagnostics.
  •  
43.
  • Pardon, Gaspard, 1983-, et al. (författare)
  • Simultaneous replication of hydrophilic and superhydrophobic micropatterns through area-selective monomer self-assembly
  • 2016
  • Ingår i: Advanced Materials Interfaces. - Weinheim : Wiley-VCH Verlagsgesellschaft. - 2196-7350. ; 3:17
  • Tidskriftsartikel (refereegranskat)abstract
    • The control and permanent modification of the surface properties of polymers is a critical enabler for many applications. Here, we demonstrate a strategy, which we call surface energy mimicking, for the spontaneous replication of micropatterns of surface energies ranging from hydrophilic to superhydrophobic from a mold to several replicas.We introduce surface energy mimicking, enabling spontaneous replication of micropatterns (2D and 2.5D) of different surface energies, and enabled by self-assembly of functional mimicking monomers within a polymer matrix. We demonstrate replication of surface energies ranging from hydrophilic to superhydrophobic, and self-assembly of picoliter-droplet arrays on replicated micropatterned arrays containing hydrophilic patches in a hydrophobic surface.
  •  
44.
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45.
  • Rahiminejad, Sofia, 1987, et al. (författare)
  • Rapid manufacturing of OSTE polymer RF-MEMS components
  • 2017
  • Ingår i: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - : IEEE. - 1084-6999. - 9781509050789 ; , s. 901-904
  • Konferensbidrag (refereegranskat)abstract
    • This paper reports the first RF-MEMS component in OSTE polymer. Three OSTE-based ridge gap resonators were fabricated by direct, high aspect ratio, photostructuring. The OSTE polymer's good adhesion to gold makes it suitable for RF-MEMS applications. The OSTE ridge gap resonators differ in how they were coated with gold. The OSTE-based devices are compared to each other as well as to Si-based, SU8-based, and CNT-based devices of equal design. The OSTE-based process was performed outside the cleanroom, and with a fast fabrication process (∼1 h). The OSTE-based device performance is on par with that of the other alternatives in terms of frequency, attenuation, and Q-factor.
  •  
46.
  • Rajabi, Mina, et al. (författare)
  • Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.
  •  
47.
  • Sandström, Niklas, et al. (författare)
  • Batch fabrication of polymer microfluidic cartridges for QCM sensor packaging by direct bonding
  • 2017
  • Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 27:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Quartz crystal microbalance (QCM) sensing is an established technique commonly used in laboratory based life-science applications. However, the relatively complex, multi-part design and multi-step fabrication and assembly of state-of-the-art QCM cartridges makes them unsuited for disposable applications such as point-of-care (PoC) diagnostics. In this work, we present the uncomplicated manufacturing of QCMs in polymer microfluidic cartridges. Our novel approach comprises two key innovations: the batch reaction injection molding of microfluidic parts; and the integration of the cartridge components by direct, unassisted bonding. We demonstrate molding of batches of 12 off-stoichiometry thiol-ene epoxy polymer (OSTE+) polymer parts in a single molding cycle using an adapted reaction injection molding process; and the direct bonding of the OSTE+ parts to other OSTE+ substrates, to printed circuit boards, and to QCMs. The microfluidic QCM OSTE+ cartridges were successfully evaluated in terms of liquid sealing as well as electrical properties, and the sensor performance characteristics are on par with those of commercially available QCM biosensor cartridge.
  •  
48.
  • Sandström, Niklas, 1981- (författare)
  • Integrating Biosensors for Air Monitoring and Breath-Based Diagnostics
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The air we breathe is the concern of all of us but nevertheless we only know very little about airborne particles, and especially which biological microorganisms they contain. Today, we live in densely populated societies with a growing number of people, making us particularly vulnerable to air transmission of pathogens. With the recent appearance of highly pathogenic types of avian influenza in southeast Asia and the seasonal outbreaks of gastroenteritis caused by the extremely contagious norovirus, the need for portable, sensitive and rapid instruments for on-site detection and monitoring of airborne pathogens is apparent.Unfortunately, the integration incompatibility between state-of-the-art air sampling techniques and laboratory based analysis methods makes instruments for in-the-field rapid detection of airborne particles an unresolved challenge.This thesis aims at addressing this challenge by the development of novel manufacturing, integration and sampling techniques to enable the use of label-free biosensors for rapid and sensitive analysis of airborne particles at the point-of-care or in the field.The first part of the thesis introduces a novel reaction injection molding technique for the fabrication of high quality microfluidic cartridges. In addition, electrically controlled liquid aspiration and dispensing is presented, based on the use of a thermally actuated polymer composite integrated with microfluidic cartridges.The second part of the thesis demonstrates three different approaches of biosensor integration with microfluidic cartridges, with a focus on simplifying the design and integration to enable disposable use of the cartridges.The third part to the thesis presents a novel air sampling technique based on electrophoretic transport of airborne particles directly to microfluidic cartridges. This technique is enabled by the development of a novel microstructured component for integrated air-liquid interfacing. In addition, a method for liquid sample mixing with magnetic microbeads prior to downstream biosensing is demonstrated.In the fourth part of the thesis, three different applications for airborne particle biosensing are introduced and preliminary experimental results are presented.
  •  
49.
  • Sandström, Niklas, 1981-, et al. (författare)
  • Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices
  • 2015
  • Ingår i: Journal of Micromechanics and Microengineering. - : Institute of Physics (IOP). - 0960-1317 .- 1361-6439. ; 25:7
  • Tidskriftsartikel (refereegranskat)abstract
    • In this article, we present OSTE+RIM, a novel reaction injection molding (RIM) process that combines the merits of off-stoichiometric thiol–ene epoxy (OSTE+) thermosetting polymers with the fabrication of high quality microstructured parts. The process relies on the dual polymerization reactions of OSTE+ polymers, where the first curing step is used in OSTE+RIM for molding intermediately polymerized parts with well-defined shapes and reactive surface chemistries. In the facile back-end processing, the replicated parts are directly and covalently bonded and become fully polymerized using the second curing step, generating complete microfluidic devices. To achieve unprecedented rapid processing, high replication fidelity and low residual stress, OSTE+RIM uniquely incorporates temperature stabilization and shrinkage compensation of the OSTE+ polymerization during molding. Two different OSTE+ formulations were characterized and used for the OSTE+RIM fabrication of optically transparent, warp-free and natively hydrophilic microscopy glass slide format microfluidic demonstrator devices, featuring a storage modulus of 2.3 GPa and tolerating pressures of at least 4 bars. 
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50.
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