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  • 1.
    Guo, Weijin
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Capillary Pumping Independent Of Liquid Sample Viscosity2016In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827Article in journal (Refereed)
    Abstract [en]

    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.

    Download full text (pdf)
    viscosity
  • 2.
    Guo, Weijin
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Capillary pumping independent of the liquid surface energy and viscosity2018In: Microsystems & Nanoengineering, ISSN 2055-7434, Vol. 4, no 2Article in journal (Refereed)
    Abstract [en]

    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.

    Download full text (pdf)
    capillary pump
  • 3.
    Guo, Weijin
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Capillary pumping with a constant flow rate independent of the liquid sample viscosity and surface energy2017In: Proceeding of 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS), IEEE, 2017Conference paper (Refereed)
    Abstract [en]

    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.

    Download full text (pdf)
    viscosity and surface energy
  • 4.
    Guo, Weijin
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Synthetic microfluidic paper with superior fluorescent signal readout2019In: Proceedings of The 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, 2019, p. 1056-1057Conference paper (Refereed)
    Abstract [en]

    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.

    Download full text (pdf)
    spsignal
  • 5.
    Guo, Weijin
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH Royal Institute of Technology.
    Hansson, Jonas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Mercene Labs AB.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Synthetic Paper Separates Plasma from Whole Blood with Low Protein Loss2020In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882Article in journal (Refereed)
    Abstract [en]

    The separation of plasma from whole blood is the first step in many diagnostic tests. Point-of-care tests often rely on integrated plasma filters, but protein retention in such filters limits their performance. Here, we investigate plasma separation on interlocked micropillar scaffolds ("synthetic paper") by the local agglutination of blood cells coupled with the capillary separation of the plasma. We separated clinically relevant volumes of plasma with high efficiency in a separation time on par with that of state of the art techniques. We investigated different covalent and non-covalent surface treatments (PEGMA, HEMA, BSA, O2 plasma) on our blood filter and their effect on protein recovery, and identified O2 plasma treatment and 7.9 μg/cm2 agglutination antibody as most suitable treatments. Using these treatments, we recovered at least 82% of the blood plasma proteins, more than with state-of-the-art filters. The simplicity of our device and the performance of our approach could enable better point-of-care tests.

    Download full text (pdf)
    fulltext
  • 6.
    Guo, Weijin
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Viscosity Independent Paper Microfluidic Imbibition2016In: Proceedings of The 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016, MicroTAS , 2016, p. 13-14Conference paper (Refereed)
    Abstract [en]

    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.

    Download full text (pdf)
    fulltext
  • 7.
    Guo, Weijin
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Vilaplana, Lluisa
    IQAC-CSIC.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Marco, M.-Pilar
    IQAC-CSIC.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Immunoassays on thiol-ene synthetic paper generate a superior fluorescence signal2020In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235Article in journal (Refereed)
    Abstract [en]

    The fluorescence-based detection of biological complexes on solid substrates is widely used in microarrays and lateral flow tests. Here, we investigate thiol-ene micropillar scaffold sheets (“synthetic paper”) as the solid substrate in such assays. Compared to state-of-the-art glass and nitrocellulose substrates, assays on synthetic paper provide a stronger fluorescence signal, similar or better reproducibility, lower limit of detection (LOD), and the possibility of working with lower immunoreagent concentrations. Using synthetic paper, we detected the antibiotic enrofloxacin in whole milk with a LOD of 1.64 nM, which is on par or better than the values obtained with other common tests, and much lower than the maximum level allowed by European Union regulations. The significance of these results lays in that they indicate that synthetically-derived microstructured substrate materials have the potential to improve the performance of diagnostic assays.

    The full text will be freely available from 2022-05-11 20:14
  • 8.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    From Lab to Chip – and back: Polymer microfluidic systems for sample handling in point-of-care diagnostics2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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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    Thesis
  • 9.
    Hansson, Jonas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Microfluidic blood sample preparation for rapid sepsis diagnostics2012Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Sepsis, commonly referred to as blood poisoning, is a serious medical condition characterized by a whole-body inflammatory state caused by microbial infection. Rapid treatment is crucial, however, traditional culture-based diagnostics usually takes 2-5 days.  The overall aim of the thesis is to develop microfluidic based sample preparation strategies, capable of isolating bacteria from whole blood for rapid sepsis diagnostics. 

    Although emerging technologies, such as microfluidics and “lab-on-a-chip” (LOC) devices have the potential to spur the development of protocols and affordable instruments, most often sample preparation is performed manually with procedures that involve handling steps prone to introducing artifacts, require skilled technicians and well-equipped, expensive laboratories.  Here, we propose the development of methods for fast and efficient sample preparation that can isolate bacteria from whole blood by using microfluidic techniques with potential to be incorporated in LOC systems.

    We have developed two means for high throughput bacteria isolation: size based sorting and selective lysis of blood cells. To process the large blood samples needed in sepsis diagnostics, we introduce novel manufacturing techniques that enable scalable parallelization for increased throughput in miniaturized devices.

    The novel manufacturing technique uses a flexible transfer carrier sheet, water-dissolvable release material, poly(vinyl alcohol), and a controlled polymerization inhibitor to enable highly complex polydimethylsiloxane (PDMS) structures containing thin membranes and 3D fluidic networks.

    The size based sorting utilizes inertial microfluidics, a novel particles focusing method that operates at extremely high flow rates. Inertial focusing in flow through a single inlet and two outlet, scalable parallel channel devices, was demonstrated with filtration efficiency of >95% and a flowrate of 3.2 mL/min.

    Finally, we have developed a novel microfluidic based sample preparation strategy to continuously isolate bacteria from whole blood for downstream analysis. The method takes advantage of the fact that bacteria cells have a rigid cell wall protecting the cell, while blood cells are much more susceptible to chemical lysis. Whole blood is continuously mixed with saponin for primary lysis, followed by osmotic shock in water. We obtained complete lysis of all blood cells, while more than 80% of the bacteria were readily recovered for downstream processing.

    Altogether, we have provided new bacteria isolation methods, and improved the manufacturing techniques and microfluidic components that, combined offer the potential for affordable and effective sample preparation for subsequent pathogen identification, all in an automated LOC format.

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    Licentiat J Hansson
  • 10.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hillmering, Mikael
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Leak tight vertical membrane microvalves in PDMSManuscript (preprint) (Other academic)
  • 11.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hillmering, Mikael
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Leak-tight vertical membrane microvalves2016In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 16, no 8, p. 1439-1446Article in journal (Refereed)
    Abstract [en]

    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.

  • 12.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hillmering, Mikael
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Van Der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Vertical membrane microvalves in PDMS2015In: 2015 28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS), IEEE , 2015, Vol. 2015, no February, p. 563-565Conference paper (Refereed)
    Abstract [en]

    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.

  • 13.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Karlsson, J. Mikael
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Carlborg, Carl Fredrik
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Low gas permeable and non-absorbent rubbery OSTE+ for pneumatic microvalves2014In: Proceedings of the 27th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2014), IEEE conference proceedings, 2014, p. 987-990Conference paper (Refereed)
    Abstract [en]

    In this paper we introduce a new polymer for use in microfluidic applications, based on the off-stoichiometric thiol–ene-epoxy (OSTE+) polymer system, but with rubbery properties. We characterize and benchmark the new polymer against PDMS. We demonstrate that Rubbery OSTE+: has more than 90% lower permeability to gases compared to PDMS, has little to no absorption of dissolved molecules, can be layer bonded in room temperature without the need for adhesives or plasma treatment, can be structured by standard micro-molding manufacturing, and shows similar performance as PDMS for pneumatic microvalves, albeit allowing handling of larger pressure. 

    Download full text (pdf)
    fulltext
  • 14.
    Hansson, Jonas
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Karlsson, J. Mikael
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Wijngaart, Wouter van der
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Russom, Aman
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Inertial Particle Focusing In Parallel Microfluidic Channels For High-Throughput Filtration2011In: 16th International  Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 2011, IEEE conference proceedings, 2011, p. 1777-1780Conference paper (Refereed)
    Abstract [en]

    In this study, we introduce inertial microfluidics in straight, parallel channels for high-throughput particle filtration. We show that particles flowing through low aspect ratio rectangular microchannels can be focused into four particle streams, distributed at the centers of each wall face, or into two particle streams, at the centers of the longest channel walls, depending on the particles' size. For high-throughput filtration, we fabricated scalable, single inlet and two outlet, parallel channel microdevices, using a high-density 3D microfluidic PDMS channel manufacturing technology, in a design that allows for easy integration with other downstream on-chip functions we recently described. We demonstrate filtration of 24 μm particles from a suspension mixture in a microdevice with four parallel channels. The filtration efficiency at a non-optimized flow rate of 0.8 ml/min was 82%.

    Download full text (pdf)
    Inertial Particle Focusing In Parallel Microfluidic Channels For High-Throughput Filtration
  • 15.
    Hansson, Jonas
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    Karlsson, Mikael J.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Russom, Aman
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    Inertial microfluidics in parallel channels for high-throughput applications2012In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, no 22, p. 4644-4650Article in journal (Refereed)
    Abstract [en]

    Passive particle focusing based on inertial microfluidics was recently introduced as a high-throughput alternative to active focusing methods that require an external force-field to manipulate particles. In this study, we introduce inertial microfluidics in flows through straight, multiple parallel channels. The scalable, single inlet and two outlet, parallel channel system is enabled by a novel, high-density 3D PDMS microchannel manufacturing technology, mediated via a targeted inhibition of PDMS polymerization. Using single channels, we first demonstrate how randomly distributed particles can be focused into the centre position of the channel in flows through low aspect ratio channels and can be effectively fractionated. As a proof of principle, continuous focusing and filtration of 10 μm particles from a suspension mixture using 4- and 16-parallel-channel devices with a single inlet and two outlets are demonstrated. A filtration efficiency of 95-97% was achieved at throughputs several orders of magnitude higher than previously shown for flows through straight channels. The scalable and low-footprint focusing device requiring neither external force fields nor mechanical parts to operate is readily applicable for high-throughput focusing and filtration applications as a stand-alone device or integrated with lab-on-a-chip systems.

    Download full text (pdf)
    fulltext
  • 16.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Quelennec, Aurore
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Yasuga, Hiroki
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    Van Der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Synthetic microfluidic paper allows controlled receptor positioning and improved readout signal intensity in lateral flow assays2015In: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Chemical and Biological Microsystems Society , 2015, p. 284-286Conference paper (Refereed)
    Abstract [en]

    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.

  • 17.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Quelennec, Aurore
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Yasuga, Hiroki
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Synthetic Microfluidic Paper allows controlled receptor positioning and improvedreadout signal intensity in lateral flow assaysManuscript (preprint) (Other academic)
  • 18.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Yasuga, Hiroki
    Basak, Sarthak
    Mercene Labs, Stockholm, SWEDEN.
    Carlborg, C. Fredrik
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Direct Lithography of Rubbery OSTE+ Polymer2014In: Proceedings 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS2014), 14CBMS , 2014, p. 123-125Conference paper (Refereed)
    Abstract [en]

    We present a Rubbery, Off-Stoichiometric Thiol-Ene-epoxy (OSTE+) polymer for direct lithography manufacturing, demonstrate its use in pneumatic pinch microvalves for lab-on-chip applications, test the lithography process achieving pillars of aspect-ratios (a.r.) 1:8, and characterize it’s surface as hydrophilic.

    Download full text (pdf)
    Hansson_2014_Direct Lithography of Rubbery OSTE+ Polymer.PDF
  • 19.
    Hansson, Jonas
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Yasuga, Hiroki
    Haraldsson, Klas Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Synthetic paper2017Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    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.

  • 20.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Yasuga, Hiroki
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Synthetic microfluidic paper2015In: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS), IEEE conference proceedings, 2015, no February, p. 10-13Conference paper (Refereed)
    Abstract [en]

    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.

  • 21.
    Hauser, Janosch
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Lenk, Gabriel
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Beck, Olof
    Karolinska Inst, Dept Lab Med, S-14186 Stockholm, Sweden..
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    High-Yield Passive Plasma Filtration from Human Finger Prick Blood2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 22, p. 13393-13399Article in journal (Refereed)
    Abstract [en]

    Whole-blood microsampling provides many benefits such as remote, patient-centric, and minimally invasive sampling. However, blood plasma, and not whole blood, is the prevailing matrix in clinical laboratory investigations. The challenge with plasma microsampling is to extract plasma volumes large enough to reliably detect low-concentration analytes from a small finger prick sample. Here we introduce a passive plasma filtration device that provides a high extraction yield of 65%, filtering 18 mu L of plasma from 50 mu L of undiluted human whole blood (hematocrit 45%) within less than 10 min. The enabling design element is a wedge-shaped connection between the blood filter and the hydrophilic bottom surface of a capillary channel. Using finger prick and venous blood samples from more than 10 healthy volunteers, we examined the filtration kinetics of the device over a hematocrit range of 35-55% and showed that 73 +/- 8% of the total protein content was successfully recovered after filtration. The presented plasma filtration device tackles a major challenge toward patient-centric blood microsampling by providing high-yield plasma filtration, potentially allowing reliable detection of low-concentration analytes from a blood microsample.

  • 22.
    Jonas, Hansson
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Yasuga, Hiroki
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Synthetic microfluidic paper: high surface area and high porosity polymer micropillar arrays2016In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 16, no 2, p. 298-304Article in journal (Refereed)
    Abstract [en]

    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.

    Download full text (pdf)
    Hansson_2016_Synthetic-microfluidic-paper.pdf
  • 23.
    Karlsson, J. Mikael
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Leak-tight vertical membrane microvalves in PDMS enabled by a novel 3D manufacturing processManuscript (preprint) (Other academic)
  • 24.
    Karlsson, J. Mikael
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Carlborg, Carl Fredrik
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Hansson, Jonas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Fabrication and transfer of fragile 3D PDMS microstructures2012In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 22, no 8, p. 1-9Article in journal (Refereed)
    Abstract [en]

    We present a method for PDMS microfabrication of fragile membranes and 3D fluidic networks, using a surface modified water-dissolvable release material, poly(vinyl alcohol), as a tool for handling, transfer and release of fragile polymer microstructures. The method is well suited for the fabrication of complex multilayer microfluidic devices, here shown for a PDMS device with a thin gas permeable membrane and closely spaced holes for vertical interlayer connections fabricated in a single layer. To the authors knowledge, this constitutes the most advanced PDMS fabrication method for the combination of thin, fragile structures and 3D fluidics networks, and hence a considerable step in the direction of making PDMS fabrication of complex microfluidic devices a routine endeavour.

    Download full text (pdf)
    fulltext
  • 25.
    Lenk, Gabriel
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Beck, Olof
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    The effect of drying on the homogeneity of DBS2015In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 7, no 16, p. 1977-1985Article in journal (Refereed)
    Abstract [en]

    Background: Inhomogeneous sample distribution in DBS is a problem for accurate quantitative analysis of DBS, and has often been explained by chromatographic effects. Results: We present a model describing formation of inhomogeneous DBS during drying of the spot caused by higher evaporation rates of water at the edge as compared with the center. Color intensity analysis shows that the relative humidity and DBS card position affect the homogeneity of DBS. Conclusion: The so-called coffee-stain effect' explains the typical distribution pattern of analytes with higher concentrations measured along the edge of DBS as compared with the center. The driving mechanism and potential influencing factors should be considered when addressing the inhomogeneity of DBS in the future.

  • 26.
    Lenk, Gabriel
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Wouter van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Capillary driven and volume-metred blood-plasma separation2015In: Proceedings 18 th IEEE Transducers, IEEE , 2015, no 16, p. 335-338Conference paper (Refereed)
    Abstract [en]

    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.

  • 27.
    Periyannan Rajeswari, Prem Kumar
    et al.
    KTH, School of Biotechnology (BIO), Bioprocess Technology (closed 20130101). KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ramachandraiah, Harisha
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Hansson, Jonas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ardabili, Sahar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Veide, Andres
    KTH, School of Biotechnology (BIO), Bioprocess Technology (closed 20130101).
    Russom, Aman
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Development of microfluidic aqueous two-phase system for continuous partitioning of E. coli strains2011In: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011, MicroTAS 2011, 2011, p. 1329-1331Conference paper (Refereed)
    Abstract [en]

    The interaction of bacterial cells with surrounding environment depends on its surface characteristics such as hydrophobicity, hydrophilicity balance and net charge. In this paper, aqueous two-phase system partitioning of Escherichia coli strains based on their difference in surface properties is introduced in a microfluidic system. While aqueous two-phase system is widely use to separate biomolecules on macroscale, the method has not been adapted in microfluidic system. The bacterial cells are partitioned based on their affinity for streams formed by aqueous polymers polyethylene glycol (PEG) and dextran (Dex). Partitioning efficiency of two Escherichia coli strains is currently being optimized.

  • 28. Rahiminejad, S.
    et al.
    Hansson, Jonas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems. KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kohler, E.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Klas Tommy
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology. KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haasl, Sjoerd
    KTH, School of Technology and Health (STH), Centres, Centre for Technology in Medicine and Health, CTMH. KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Enoksson, P.
    Rapid manufacturing of OSTE polymer RF-MEMS components2017In: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS), IEEE, 2017, p. 901-904Conference paper (Refereed)
    Abstract [en]

    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.

  • 29.
    Yada, Susumu
    et al.
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Bagheri, Shervin
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Hansson, Jonas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Do-Quang, Minh
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Lundell, Fredrik
    KTH, School of Engineering Sciences (SCI), Mechanics.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Amberg, Gustav
    KTH, School of Engineering Sciences (SCI), Mechanics. Södertorn University, Stockholm, Sweden .
    Droplet leaping governs microstructured surface wetting2019In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 15, no 46, p. 9528-9536Article in journal (Refereed)
    Abstract [en]

    Microstructured surfaces that control the direction of liquid transport are not only ubiquitous in nature, but they are also central to technological processes such as fog/water harvesting, oil–water separation, and surface lubrication. However, a fundamental understanding of the initial wetting dynamics of liquids spreading on such surfaces is lacking. Here, we show that three regimes govern microstructured surface wetting on short time scales: spread, stick, and contact line leaping. The latter involves establishing a new contact line downstream of the wetting front as the liquid leaps over specific sections of the solid surface. Experimental and numerical investigations reveal how different regimes emerge in different flow directions during wetting of periodic asymmetrically microstructured surfaces. These insights improve our understanding of rapid wetting in droplet impact, splashing, and wetting of vibrating surfaces and may contribute to advances in designing structured surfaces for the mentioned applications.

  • 30. Zelenin, S.
    et al.
    Ramachandraiah, Harisha
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Hansson, Jonas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ardabili, Sahar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. Karolinska Institutet, Sweden.
    Russom, Aman
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Bacteria isolation from whole blood for sepsis diagnostics2011In: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011, MicroTAS 2011, 2011, p. 518-520Conference paper (Refereed)
    Abstract [en]

    Rapid and reliable detection of bloodstream infections would gain a lot from improved and straightforward isolation of highly purified bacteria from whole blood. Here, we report a microfluidics-based sample preparation strategy to continuously isolate microorganisms from whole blood for downstream analysis. The continuous-flow method takes advantage of the fact that bacteria cells have rigid cell wall enables selective and complete blood cell lysis while ~ 100% of bacteria are readily recovered. The method as a sample preparation unit offers opportunities to develop molecular based POC for sepsis diagnostics.

  • 31.
    Zelenin, Sergey
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hansson, Jonas
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ardabili, Sahar
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Microfluidic-based isolation of bacteria from whole blood for sepsis diagnostics2015In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 37, no 4, p. 825-830Article in journal (Refereed)
    Abstract [en]

    Blood-stream infections (BSI) remain a major health challenge, with an increasing incidence worldwide and a high mortality rate. Early treatment with appropriate antibiotics can reduce BSI-related morbidity and mortality, but success requires rapid identification of the infecting organisms. The rapid, culture-independent diagnosis of BSI could be significantly facilitated by straightforward isolation of highly purified bacteria from whole blood. We present a microfluidic-based, sample-preparation system that rapidly and selectively lyses all blood cells while it extracts intact bacteria for downstream analysis. Whole blood is exposed to a mild detergent, which lyses most blood cells, and then to osmotic shock using deionized water, which eliminates the remaining white blood cells. The recovered bacteria are 100 % viable, which opens up possibilities for performing drug susceptibility tests and for nucleic-acid-based molecular identification.

  • 32. Zelenin, Sergey
    et al.
    Hansson, Jonas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ramachandraiah, Harisha
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ardabili, Sahar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    Microfluidic selective cell lysis for bacteria isolation from whole bloodManuscript (preprint) (Other academic)
1 - 32 of 32
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