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1.
  • Ahmad Tajudin, Asilah, et al. (författare)
  • Integrated acoustic immunoaffinity-capture (IAI) platform for detection of PSA from whole blood samples.
  • 2013
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 13:9, s. 1790-1796
  • Tidskriftsartikel (refereegranskat)abstract
    • On-chip detection of low abundant protein biomarkers is of interest to enable point-of-care diagnostics. Using a simple form of integration, we have realized an integrated microfluidic platform for the detection of prostate specific antigen (PSA), directly in anti-coagulated whole blood. We combine acoustophoresis-based separation of plasma from undiluted whole blood with a miniaturized immunoassay system in a polymer manifold, demonstrating improved assay speed on our Integrated Acoustic Immunoaffinity-capture (IAI) platform. The IAI platform separates plasma from undiluted whole blood by means of acoustophoresis and provides cell free plasma of clinical quality at a rate of 10 uL/min for an online immunoaffinity-capture of PSA on a porous silicon antibody microarray. The whole blood input (hematocrit 38-40%) rate was 50 μl min(-1) giving a plasma volume fraction yield of ≈33%. PSA was immunoaffinity-captured directly from spiked female whole blood samples at clinically significant levels of 1.7-100 ng ml(-1) within 15 min and was subsequently detected via fluorescence readout, showing a linear response over the entire range with a coefficient of variation of 13%.
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2.
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3.
  • Ainla, Alar, 1982, et al. (författare)
  • A multifunctional pipette
  • 2012
  • Ingår i: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 12:7, s. 1255-1261
  • Tidskriftsartikel (refereegranskat)abstract
    • Microfluidics has emerged as a powerful laboratory toolbox for biologists, allowing manipulation and analysis of processes at a cellular and sub-cellular level, through utilization of microfabricated features at size-scales relevant to that of a single cell. In the majority of microfluidic devices, sample processing and analysis occur within closed microchannels, imposing restrictions on sample preparation and use. We present an optimized non-contact open-volume microfluidic tool to overcome these and other restrictions, through the use of a hydrodynamically confined microflow pipette, serving as a multifunctional solution handling and dispensing tool. The geometries of the tool have been optimised for use in optical microscopy, with integrated solution reservoirs to reduce reagent use, contamination risks and cleaning requirements. Device performance was characterised using both epifluorescence and total internal reflection fluorescence (TIRF) microscopy, resulting in similar to 200 ms and similar to 130 ms exchange times at similar to 100 nm and similar to 30 mm distances to the surface respectively.
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4.
  • Ainla, Alar, 1982, et al. (författare)
  • Single-cell electroporation using a multifunctional pipette
  • 2012
  • Ingår i: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 12:22, s. 4605-4609
  • Tidskriftsartikel (refereegranskat)abstract
    • We present here a novel platform combination, using a multifunctional pipette to individually electroporate single-cells and to locally deliver an analyte, while in their culture environment. We demonstrate a method to fabricate low-resistance metallic electrodes into a PDMS pipette, followed by characterization of its effectiveness, benefits and limits in comparison with an external carbon microelectrode.
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5.
  • Andersson, Helene, et al. (författare)
  • Microfabrication and microfluidics for tissue engineering : state of the art and future opportunities
  • 2004
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 4:2, s. 98-103
  • Forskningsöversikt (refereegranskat)abstract
    • An introductory overview of the use of microfluidic devices for tissue engineering is presented. After a brief description of the background of tissue engineering, different application areas of microfluidic devices are examined. Among these are methods for patterning cells, topographical control over cells and tissues, and bioreactors. Examples where microfluidic devices have been employed are presented such as basal lamina, vascular tissue, liver, bone, cartilage and neurons. It is concluded that until today, microfluidic devices have not been used extensively in tissue engineering. Major contributions are expected in two areas. The first is growth of complex tissue, where microfluidic structures ensure a steady blood supply, thereby circumventing the well-known problem of providing larger tissue structures with a continuous flow of oxygen and nutrition, and withdrawal of waste products. The second, and probably more important function of microfluidics, combined with micro/nanotechnology, lies in the development of in vitro physiological systems for studying fundamental biological phenomena.
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6.
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7.
  • Andersson, Martin, et al. (författare)
  • A microscopy-compatible temperature regulation system for single-cell phenotype analysis - demonstrated by thermoresponse mapping of microalgae
  • 2021
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 21:9, s. 1694-1705
  • Tidskriftsartikel (refereegranskat)abstract
    • This work describes a programmable heat-stage compatible with in situ microscopy for the accurate provision of spatiotemporally defined temperatures to different microfluidic devices. The heat-stage comprises an array of integrated thin-film Joule heaters and resistance temperature detectors (RTDs). External programming of the heat-stage is provided by a custom software program connected to temperature controllers and heater–sensor pairs. Biologically relevant (20–40 °C) temperature profiles can be supplied to cells within microfluidic devices as spatial gradients (0.5–1.5 °C mm−1) or in a time-varying approach via e.g. step-wise or sinusoidally varying profiles with negligible temperature over-shoot. Demonstration of the device is achieved by exposing two strains of the coral symbiont Symbiodinium to different temperature profiles while monitoring their single-cell photophysiology via chlorophyll fluorometry. This revealed that photophysiological responses to temperature depended on the exposure duration, exposure magnitude and strain background. Moreover, thermal dose analysis suggested that cell acclimatisation occurs under longer temperature (6 h) exposures but not under shorter temperature exposures (15 min). As the thermal sensitivity of Symbiodinium mediates the thermal tolerance in corals, our versatile technology now provides unique possibilities to research this interdependency at single cell resolution. Our results also show the potential of this heat-stage for further applications in fields such as biotechnology and ecotoxicology.
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8.
  • Andersson Svahn, Helene, et al. (författare)
  • Single cells or large populations?
  • 2007
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 7:5, s. 544-546
  • Tidskriftsartikel (refereegranskat)
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9.
  • Antfolk, Maria, et al. (författare)
  • Focusing of sub-micrometer particles and bacteria enabled by two-dimensional acoustophoresis.
  • 2014
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189. ; 14:15, s. 2791-2799
  • Tidskriftsartikel (refereegranskat)abstract
    • Handling of sub-micrometer bioparticles such as bacteria are becoming increasingly important in the biomedical field and in environmental and food analysis. As a result, there is an increased need for less labor-intensive and time-consuming handling methods. Here, an acoustophoresis-based microfluidic chip that uses ultrasound to focus sub-micrometer particles and bacteria, is presented. The ability to focus sub-micrometer bioparticles in a standing one-dimensional acoustic wave is generally limited by the acoustic-streaming-induced drag force, which becomes increasingly significant the smaller the particles are. By using two-dimensional acoustic focusing, i.e. focusing of the sub-micrometer particles both horizontally and vertically in the cross section of a microchannel, the acoustic streaming velocity field can be altered to allow focusing. Here, the focusability of E. coli and polystyrene particles as small as 0.5 μm in diameter in microchannels of square or rectangular cross sections, is demonstrated. Numerical analysis was used to determine generic transverse particle trajectories in the channels, which revealed spiral-shaped trajectories of the sub-micrometer particles towards the center of the microchannel; this was also confirmed by experimental observations. The ability to focus and enrich bacteria and other sub-micrometer bioparticles using acoustophoresis opens the research field to new microbiological applications.
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10.
  • Antypas, H., et al. (författare)
  • A universal platform for selection and high-resolution phenotypic screening of bacterial mutants using the nanowell slide
  • 2018
  • Ingår i: Lab on a Chip. - : ROYAL SOC CHEMISTRY. - 1473-0197 .- 1473-0189. ; 18:12, s. 1767-1777
  • Tidskriftsartikel (refereegranskat)abstract
    • The Petri dish and microtiter plate are the golden standard for selection and screening of bacteria in microbiological research. To improve on the limited resolution and throughput of these methods, we developed a universal, user-friendly platform for selection and high-resolution phenotypic screening based on the nanowell slide. This miniaturized platform has an optimal ratio between throughput and assay complexity, holding 672 nanowells of 500 nl each. As monoclonality is essential in bacterial genetics, we used FACS to inoculate each nanowell with a single bacterium in 15 min. We further extended the protocol to select and sort only bacteria of interest from a mixed culture. We demonstrated this by isolating single transposon mutants generated by a custom-made transposon with dual selection for GFP fluorescence and kanamycin resistance. Optical compatibility of the nanowell slide enabled phenotypic screening of sorted mutants by spectrophotometric recording during incubation. By processing the absorbance data with our custom algorithm, a phenotypic screen for growth-associated mutations was performed. Alternatively, by processing fluorescence data, we detected metabolism-associated mutations, exemplified by a screen for -galactosidase activity. Besides spectrophotometry, optical compatibility enabled us to perform microscopic analysis directly in the nanowells to screen for mutants with altered morphologies. Despite the miniaturized format, easy transition from nano- to macroscale cultures allowed retrieval of bacterial mutants for downstream genetic analysis, demonstrated here by a cloning-free single-primer PCR protocol. Taken together, our FACS-linked nanowell slide replaces manual selection of mutants on agar plates, and enables combined selection and phenotypic screening in a one-step process. The versatility of the nanowell slide, and the modular workflow built on mainstream technologies, makes our universal platform widely applicable in microbiological research.
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11.
  • Armbrecht, L., et al. (författare)
  • Self-assembled magnetic bead chains for sensitivity enhancement of microfluidic electrochemical biosensor platforms
  • 2015
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 15:22, s. 4314-4321
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we present a novel approach to enhance the sensitivity of microfluidic biosensor platforms with self-assembled magnetic bead chains. An adjustable, more than 5-fold sensitivity enhancement is achieved by introducing a magnetic field gradient along a microfluidic channel by means of a soft-magnetic lattice with a 350 mu m spacing. The alternating magnetic field induces the self-assembly of the magnetic beads in chains or clusters and thus improves the perfusion and active contact between the analyte and the beads. The soft-magnetic lattices can be applied independent of the channel geometry or chip material to any microfluidic biosensing platform. At the same time, the bead-based approach achieves chip reusability and shortened measurement times. The bead chain properties and the maximum flow velocity for bead retention were validated by optical microscopy in a glass capillary. The magnetic actuation system was successfully validated with a biotin-streptavidin model assay on a low-cost electrochemical microfluidic chip, fabricated by dry-film photoresist technology (DFR). Labelling with glucose oxidase (GOx) permits rapid electrochemical detection of enzymatically produced H2O2.
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12.
  • Asri, Mohd Afiq Mohd, et al. (författare)
  • Low-cost and rapid prototyping of integrated electrochemical microfluidic platforms using consumer-grade off-the-shelf tools and materials
  • 2022
  • Ingår i: Lab on a Chip. - : ROYAL SOC CHEMISTRY. - 1473-0197 .- 1473-0189. ; 22:9, s. 1779-1792
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a low-cost, accessible, and rapid fabrication process for electrochemical microfluidic sensors. This work leverages the accessibility of consumer-grade electronic craft cutters as the primary tool for patterning of sensor electrodes and microfluidic circuits, while commodity materials such as gold leaf, silver ink pen, double-sided tape, plastic transparency films, and fabric adhesives are used as its base structural materials. The device consists of three layers, the silver reference electrode layer at the top, the PET fluidic circuits in the middle and the gold sensing electrodes at the bottom. Separation of the silver reference electrode from the gold sensing electrodes reduces the possibility of cross-contamination during surface modification. A novel approach in mesoscale patterning of gold leaf electrodes can produce generic designs with dimensions as small as 250 mu m. Silver electrodes with dimensions as small as 385 mu m were drawn using a plotter and a silver ink pen, and fluid microchannels as small as 300 mu m were fabricated using a sandwich of iron-on adhesives and PET. Device layers are then fused together using an office laminator. The integrated microfluidic electrochemical platform has electrode kinetics/performance of Delta E-p = 91.3 mV, I-pa/I-pc = 0.905, characterized by cyclic voltammetry using a standard ferrocyanide redox probe, and this was compared against a commercial screen-printed gold electrode (Delta E-p = 68.9 mV, I-pa/I-pc = 0.984). To validate the performance of the integrated microfluidic electrochemical platform, a catalytic hydrogen peroxide sensor and enzyme-coupled glucose biosensors were developed as demonstrators. Hydrogen peroxide quantitation achieves a limit of detection of 0.713 mM and sensitivity of 78.37 mu A mM(-1) cm(-2), while glucose has a limit of detection of 0.111 mM and sensitivity of 12.68 mu A mM(-1) cm(-2). This rapid process allows an iterative design-build-test cycle in under 2 hours. The upfront cost to set up the system is less than USD 520, with each device costing less than USD 0.12, making this manufacturing process suitable for low-resource laboratories or classroom settings.
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13.
  • Augustsson, Per, et al. (författare)
  • Acoustofluidics 11: Affinity specific extraction and sample decomplexing using continuous flow acoustophoresis.
  • 2012
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 12:10, s. 1742-1752
  • Tidskriftsartikel (refereegranskat)abstract
    • Acoustic standing wave technology combined with ligand complexed microbeads offers a means for affinity specific selection of target analytes from complex samples. When realized in a microfluidic format we can capitalize on laminar flow and acoustic forces that can drive cells or microbeads across fluid interfaces. Given this, we have the ability to perform carrier fluid (suspending medium) exchange operations in continuous flow in microfluidic chips based solely on acoustofluidic properties. A key issue here is to ensure that a minimum of the original carrier fluid follows the cells/particles across the fluid interface. Simple processing protocols can be achieved that may outperform macroscale magnetic bead-based sample extraction or centrifugation steps, which can also be straightforwardly integrated with downstream analytical instrumentation. This tutorial outlines some basic fluidic configurations for acoustophoresis based sample decomplexing and details the different system parameters that will impact the outcome of an acoustophoresis based affinity extraction experiment or a cell medium exchange step. Examples are given of both targeted extraction of microbes and selective elusion of molecular species.
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14.
  • Augustsson, Per, et al. (författare)
  • Automated and temperature-controlled micro-PIV measurements enabling long-term-stable microchannel acoustophoresis characterization.
  • 2011
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 11:24, s. 4152-4164
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a platform for micro particle image velocimetry (μPIV), capable of carrying out full-channel, temperature-controlled, long-term-stable, and automated μPIV-measurement of microchannel acoustophoresis with uncertainties below 5% and a spatial resolution in the order of 20 μm. A method to determine optimal μPIV-settings for obtaining high-quality results of the spatially inhomogeneous acoustophoretic velocity fields of large dynamical range is presented. In particular we study the dependence of the results on the μPIV interrogation window size and the number of repeated experiments. The μPIV-method was further verified by comparing it with our previously published particle tracking method. Using the μPIV platform we present a series of high-resolution measurements of the acoustophoretic velocity field as a function of the driving frequency, the driving voltage, and the resonator temperature. Finally, we establish a direct and consistent connection between the obtained acoustophoretic velocity fields, and continuous flow mode acoustophoresis, commonly used in applications.
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15.
  • Banerjee, Indradumna, et al. (författare)
  • Microfluidic centrifugation assisted precipitation based DNA quantification
  • 2019
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 19:9, s. 1657-1664
  • Tidskriftsartikel (refereegranskat)abstract
    • Nucleic acid amplification methods are increasingly being used to detect trace quantities of DNA in samples for various diagnostic applications. However, quantifying the amount of DNA from such methods often requires time consuming purification, washing or labeling steps. Here, we report a novel microfluidic centrifugation assisted precipitation (mu CAP) method for single-step DNA quantification. The method is based on formation of a visible precipitate, which can be quantified, when an intercalating dye (GelRed) is added to the DNA sample and centrifuged for a few seconds. We describe the mechanism leading to the precipitation phenomenon. We utilize centrifugal microfluidics to precisely control the formation of the visible and quantifiable mass. Using a standard CMOS sensor for imaging, we report a detection limit of 45 ng mu l(-1). Furthermore, using an integrated lab-on-DVD platform we recently developed, the detection limit is lowered to 10 ng mu l(-1), which is comparable to those of current commercially available instruments for DNA quantification. As a proof of principle, we demonstrate the quantification of LAMP products for a HIV-1B type genome containing plasmid on the lab-on-DVD platform. The simple DNA quantification system could facilitate advanced point of care molecular diagnostics.
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16.
  • Barkefors, Irmeli, et al. (författare)
  • A fluidic device to study directional angiogenesis in complex tissue and organ culture models
  • 2009
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 9:4, s. 529-535
  • Tidskriftsartikel (refereegranskat)abstract
    • Many signals that induce angiogenesis have been identified; however, it is still not clear how these signals interact to shape the vascular system. We have developed a fluidic device for generation of molecular gradients in 3-dimensional cultures of complex tissues and organs in order to create an assay for precise induction and guidance of growing blood vessels. The device features a centrally placed culture chamber, flanked by channels attached to a perfusion system used to generate gradients. A separate network of vacuum channels permits reversible attachment of the device to a flat surface. We show that the fluidic device can be used to create growth factor gradients that induce directional angiogenesis in embryonic mouse kidneys and in clusters of differentiating stem cells. These results demonstrate that the device can be used to accurately manipulate complex morphogenetic processes with a high degree of experimental control.
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17.
  • Barnkob, Rune, et al. (författare)
  • Measuring acoustic energy density in microchannel acoustophoresis using a simple and rapid light-intensity method
  • 2012
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 12:13, s. 2337-2344
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a simple and rapid method for measuring the acoustic energy density in microchannel acoustophoresis based on light-intensity measurements of a suspension of particles. The method relies on the assumption that each particle in the suspension undergoes single-particle acoustophoresis. It is validated by the single-particle tracking method, and we show by proper re-scaling that the re-scaled light intensity plotted versus re-scaled time falls on a universal curve. The method allows for analysis of moderate-resolution images in the concentration range encountered in typical experiments, and it is an attractive alternative to particle tracking and particle image velocimetry for quantifying acoustophoretic performance in microchannels.
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18.
  • Barnkob, Rune, et al. (författare)
  • Measuring the local pressure amplitude in microchannel acoustophoresis
  • 2010
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 10:5, s. 563-570
  • Tidskriftsartikel (refereegranskat)abstract
    • A new method is reported on how to measure the local pressure amplitude and the Q factor of ultrasound resonances in microfluidic chips designed for acoustophoresis of particle suspensions. The method relies on tracking individual polystyrene tracer microbeads in straight water-filled silicon/glass microchannels. The system is actuated by a PZT piezo transducer attached beneath the chip and driven by an applied ac voltage near its eigenfrequency of 2 MHz. For a given frequency a number of particle tracks are recorded by a CCD camera and fitted to a theoretical expression for the acoustophoretic motion of the microbeads. From the curve fits we obtain the acoustic energy density, and hence the pressure amplitude as well as the acoustophoretic force. By plotting the obtained energy densities as a function of applied frequency, we obtain Lorentzian line shapes, from which the resonance frequency and the Q factor for each resonance peak are derived. Typical measurements yield acoustic energy densities of the order of 10 J/m(3), pressure amplitudes of 0.2 MPa, and Q factors around 500. The observed half wavelength of the transverse acoustic pressure wave is equal within 2% to the measured width w = 377 mu m of the channel.
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19.
  • Barry, Antonia, et al. (författare)
  • Investigating the effects of arginine methylation inhibitors on microdissected brain tumour biopsies maintained in a miniaturised perfusion system
  • 2023
  • Ingår i: Lab on a Chip. - 1473-0197 .- 1473-0189. ; 23:11, s. 2664-2682
  • Tidskriftsartikel (refereegranskat)abstract
    • Arginine methylation is a post-translational modification that consists of the transfer of one or two methyl (CH3) groups to arginine residues in proteins. Several types of arginine methylation occur, namely monomethylation, symmetric dimethylation and asymmetric dimethylation, which are catalysed by different protein arginine methyltransferases (PRMTs). Inhibitors of PRMTs have recently entered clinical trials to target several types of cancer, including gliomas (NCT04089449). People with glioblastoma (GBM), the most aggressive form of brain tumour, are among those with the poorest quality of life and likelihood of survival of anyone diagnosed with cancer. There is currently a lack of (pre)clinical research on the possible application of PRMT inhibitors to target brain tumours. Here, we set out to investigate the effects of clinically-relevant PRMT inhibitors on GBM biopsies. We present a new, low-cost, easy to fabricate perfusion device that can maintain GBM tissue in a viable condition for at least eight days post-surgical resection. The miniaturised perfusion device enables the treatment of GBM tissue with PRMT inhibitors ex vivo, and we observed a two-fold increase in apoptosis in treated samples compared to parallel control experiments. Mechanistically, we show thousands of differentially expressed genes after treatment, and changes in the type of arginine methylation of the RNA binding protein FUS that are consistent with hundreds of differential gene splicing events. This is the first time that cross-talk between different types of arginine methylation has been observed in clinical samples after treatment with PRMT inhibitors.
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20.
  • Beech, Jason, et al. (författare)
  • Sorting cells by size, shape and deformability
  • 2012
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 12, s. 1048-1051
  • Tidskriftsartikel (refereegranskat)abstract
    • While size has been widely used as a parameter in cellular separations, in this communication we show how shape and deformability, a mainly untapped source of specificity in preparative and analytical microfluidic devices can be measured and used to separate cells. © 2012 The Royal Society of Chemistry.
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21.
  • Beech, Jason, et al. (författare)
  • Tipping the balance of deterministic lateral displacement devices using dielectrophoresis.
  • 2009
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 9:18, s. 2698-2706
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the use of dielectrophoresis (DEP) to achieve tunability, improve dynamic range and open up for the separation of particles with regard to parameters other than hydrodynamic size in deterministic lateral displacement (DLD) devices. DLD devices have been shown capable of rapidly and continuously separating micrometer sized plastic spheres by size with a resolution of 20 nm in diameter and of being able to handle the separation of biological samples as wide ranging as bacterial artificial chromosomes and blood cells. DEP, while not exhibiting the same resolution in size separation as DLD, has the benefit of being easy to tune and can, by choosing the frequency, be used to probe a variety of particle properties. By combining DLD and DEP we open up for the advantages, while avoiding the drawbacks, of the two techniques. We present a proof of principle in which the critical size for separation of polystyrene beads is tuned in the range 2-6 microm in a single device by the application of moderate (100 V cm(-1)), low frequency (100 Hz) AC electric fields. The behaviour of the device was further investigated by performing simulations of particle trajectories, the results of which were in good qualitative agreement with experiments, indicating the potential of the method for tunable, high-resolution separations with respect to both size and polarisability.
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22.
  • Beech, Jason, et al. (författare)
  • Tuneable separation in elastomeric microfluidics devices.
  • 2008
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 8:5, s. 657-659
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe how the elastomeric properties of PDMS (polydimethylsiloxane) can be utilised to achieve tuneable particle separation in Deterministic Lateral Displacement devices via strain controlled alteration of inter-obstacle distances, a development that opens up new avenues toward more effective separation of particles in microfluidics devices.
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23.
  • Bergström, Gunnar, et al. (författare)
  • Macroporous microcarriers for introducing cells into a microfluidic chip
  • 2014
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 14:18, s. 3502-3504
  • Tidskriftsartikel (refereegranskat)abstract
    • Macroporous gelatin beads (CultiSpher™ microcarriers) provide a convenient method for rapidly and reliably introducing cells cultured ex situ into a microfluidic device, where the spheres create a 3D environment for continued cell proliferation. We demonstrate the usefulness of this technique with a proof-of-concept viability analysis of cardiac cells after treatment with doxorubicin. © 2014 the Partner Organisations.
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24.
  • Bergström, Gunnar, et al. (författare)
  • Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging
  • 2015
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 15:15, s. 3242-3249
  • Tidskriftsartikel (refereegranskat)abstract
    • Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device. Video imaging was utilized for automatic monitoring of the beating frequency of each individual CB. The device allowed assessment of cardiotoxic effects on the 3D clustered cardiomyocytes from the drug substances doxorubicin, verapamil and quinidine. Beating frequency data recorded over a period of 6 hours are presented and compared to literature data. The results indicate that this microfluidic setup with imaging of CB characteristics provides a new opportunity for label-free, non-invasive investigation of toxic effects in a 3D microenvironment.
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25.
  • Bogorad, Max I, et al. (författare)
  • Review : in vitro microvessel models.
  • 2015
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 15:22, s. 4242-55
  • Tidskriftsartikel (refereegranskat)abstract
    • A wide range of perfusable microvessel models have been developed, exploiting advances in microfabrication, microfluidics, biomaterials, stem cell technology, and tissue engineering. These models vary in complexity and physiological relevance, but provide a diverse tool kit for the study of vascular phenomena and methods to vascularize artificial organs. Here we review the state-of-the-art in perfusable microvessel models, summarizing the different fabrication methods and highlighting advantages and limitations.
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26.
  • Botte, Ermes, et al. (författare)
  • Size-related variability of oxygen consumption rates in individual human hepatic cells
  • 2024
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189.
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate descriptions of the variability in single-cell oxygen consumption and its size-dependency are key to establishingmore robust tissue models. By combining microfabricated devices with multiparameter identification algorithms, wedemonstrate that single human hepatocytes exhibit an oxygen level-dependent consumption rate and that their maximaloxygen consumption rate is significantly lower than that of typical hepatic cell cultures. Moreover, we found that clusters oftwo or more cells competing for a limited oxygen supply reduced their maximal consumption rate, highlighting their abilityto adapt to local resource availability and the presence of nearby cells. We used our approach to characterize the covarianceof size and oxygen consumption rate within a cell population, showing that size matters, since oxygen metabolism covarieslognormally with cell size. Our study paves the way for linking the metabolic activity of single human hepatocytes to theirtissue- or organ-level metabolism and describing its size-related variability through scaling laws.
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27.
  • Bridle, Helen, 1979, et al. (författare)
  • On-chip fabrication to add temperature control to a microfluidic solution exchange system
  • 2008
  • Ingår i: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 8:3, s. 480-483
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a concept for the post production modification of commercially available microfluidic devices to incorporate local temperature control, thus allowing for the exact alignment of heating structures with the existing features, e.g. wells, channels or valves, of a system. Specifically, we demonstrate the application of programmable local heating, controlled by computerized PI regulation, to a rapid solution exchanger. Characterisation of the system to show that both uniform temperature distributions and temperature gradients can be established, and to confirm that the solution exchange properties are undisturbed by heating, was achieved using in situ thermometry and amperometry. © The Royal Society of Chemistry.
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28.
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29.
  • Bryl-Górecka, Paulina, et al. (författare)
  • Effect of exercise on the plasma vesicular proteome : A methodological study comparing acoustic trapping and centrifugation
  • 2018
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 18:20, s. 3101-3111
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular vesicles (EVs) are a heterogeneous group of actively released vesicles originating from a wide range of cell types. Characterization of these EVs and their proteomes in the human plasma provides a novel approach in clinical diagnostics, as they reflect physiological and pathological states. However, EV isolation is technically challenging with the current methods having several disadvantages, requiring large sample volumes, and resulting in loss of sample and EV integrity. Here, we use an alternative, non-contact method based on a microscale acoustic standing wave technology. Improved coupling of the acoustic resonator increased the EV recovery from 30% in earlier reports to 80%, also displaying long term stability between experiment days. We report a pilot study, with 20 subjects who underwent physical exercise. Plasma samples were obtained before and 1 h after the workout. Acoustic trapping was compared to a standard high-speed centrifugation protocol, and the method was validated by flow cytometry (FCM). To monitor the device stability, the pooled frozen plasma from volunteers was used as an internal control. A key finding from the FCM analysis was a decrease in CD62E+ (E-selectin) EVs 1 h after exercise that was consistent for both methods. Furthermore, we report the first data that analyse differential EV protein expression before and after physical exercise. Olink-based proteomic analysis showed 54 significantly changed proteins in the EV fraction in response to physical exercise, whereas the EV-free plasma proteome only displayed four differentially regulated proteins, thus underlining an important role of these vesicles in cellular communication, and their potential as plasma derived biomarkers. We conclude that acoustic trapping offers a fast and efficient method comparable with high-speed centrifugation protocols. Further, it has the advantage of using smaller sample volumes (12.5 μL) and rapid contact-free separation with higher yield, and can thus pave the way for future clinical EV-based diagnostics.
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30.
  • Carlborg, Carl Fredrik, et al. (författare)
  • A packaged optical slot-waveguide ring resonator sensor array for multiplex label-free assays in labs-on-chips
  • 2010
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 10:3, s. 281-290
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the design, fabrication, and characterisation of an array of optical slot-waveguide ring resonator sensors, integrated with microfluidic sample handling in a compact cartridge, for multiplexed real-time label-free biosensing. Multiplexing not only enables high throughput, but also provides reference channels for drift compensation and control experiments. Our use of alignment tolerant surface gratings to couple light into the optical chip enables quick replacement of cartridges in the read-out instrument. Furthermore, our novel use of a dual surface-energy adhesive film to bond a hard plastic shell directly to the PDMS microfluidic network allows for fast and leak-tight assembly of compact cartridges with tightly spaced fluidic interconnects. The high sensitivity of the slot-waveguide resonators, combined with on-chip referencing and physical modelling, yields a volume refractive index detection limit of 5 x 10(-6) refractive index units (RIUs) and a surface mass density detection limit of 0.9 pg mm(-2), to our knowledge the best reported values for integrated planar ring resonators.
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31.
  • Carlborg, Carl Fredrik, et al. (författare)
  • Beyond PDMS: off-stoichiometry thiol–ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices
  • 2011
  • Ingår i: Lab on a Chip. - : RSC Publishing. - 1473-0197 .- 1473-0189. ; 11:18, s. 3136-3147
  • Tidskriftsartikel (refereegranskat)abstract
    • In this article we introduce a novel polymer platform based on off-stoichiometry thiol–enes (OSTEs), aiming to bridge the gap between research prototyping and commercial production of microfluidic devices. The polymers are based on the versatile UV-curable thiol–ene chemistry but takes advantage of off-stoichiometry ratios to enable important features for a prototyping system, such as one-step surface modifications, tuneable mechanical properties and leakage free sealing through direct UV-bonding. The platform exhibits many similarities with PDMS, such as rapid prototyping and uncomplicated processing but can at the same time mirror the mechanical and chemical properties of both PDMS as well as commercial grade thermoplastics. The OSTE-prepolymer can be cast using standard SU-8 on silicon masters and a table-top UV-lamp, the surface modifications are precisely grafted using a stencil mask and the bonding requires only a single UV-exposure. To illustrate the potential of the material we demonstrate key concepts important in microfluidic chip fabrication such as patterned surface modifications for hydrophobic stops, pneumatic valves using UV-lamination of stiff and rubbery materials as well as micromachining of chip-to-world connectors in the OSTE-materials.
  •  
32.
  • Chang, Tsung-Yao, et al. (författare)
  • Fully automated cellular-resolution vertebrate screening platform with parallel animal processing
  • 2012
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 12:4, s. 711-716
  • Tidskriftsartikel (refereegranskat)abstract
    • The zebrafish larva is an optically-transparent vertebrate model with complex organs that is widelyused to study genetics, developmental biology, and to model various human diseases. In this article, wepresent a set of novel technologies that significantly increase the throughput and capabilities of ourpreviously described vertebrate automated screening technology (VAST). We developed a robustmulti-thread system that can simultaneously process multiple animals. System throughput is limitedonly by the image acquisition speed rather than by the fluidic or mechanical processes. We developedimage recognition algorithms that fully automate manipulation of animals, including orienting andpositioning regions of interest within the microscope’s field of view. We also identified the optimalcapillary materials for high-resolution, distortion-free, low-background imaging of zebrafish larvae.
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33.
  • Cheng, Shi, et al. (författare)
  • Microfluidic electronics
  • 2012
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 12:16, s. 2782-2791
  • Tidskriftsartikel (refereegranskat)abstract
    • Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e. g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field.
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34.
  • Cheng, Shi, et al. (författare)
  • Microfluidic stretchable RF electronics
  • 2010
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 10:23, s. 3227-3234
  • Tidskriftsartikel (refereegranskat)abstract
    • Stretchable electronics is a revolutionary technology that will potentially create a world of radically different electronic devices and systems that open up an entirely new spectrum of possibilities. This article proposes a microfluidic based solution for stretchable radio frequency (RF) electronics, using hybrid integration of active circuits assembled on flex foils and liquid alloy passive structures embedded in elastic substrates, e. g. polydimethylsiloxane (PDMS). This concept was employed to implement a 900 MHz stretchable RF radiation sensor, consisting of a large area elastic antenna and a cluster of conventional rigid components for RF power detection. The integrated radiation sensor except the power supply was fully embedded in a thin elastomeric substrate. Good electrical performance of the standalone stretchable antenna as well as the RF power detection sub-module was verified by experiments. The sensor successfully detected the RF radiation over 5 m distance in the system demonstration. Experiments on two-dimensional (2D) stretching up to 15%, folding and twisting of the demonstrated sensor were also carried out. Despite the integrated device was severely deformed, no failure in RF radiation sensing was observed in the tests. This technique illuminates a promising route of realizing stretchable and foldable large area integrated RF electronics that are of great interest to a variety of applications like wearable computing, health monitoring, medical diagnostics, and curvilinear electronics.
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35.
  • Christakou, Athanasia, et al. (författare)
  • Ultrasonic three-dimensional on-chip cell culture for dynamic studies of tumor immune surveillance by natural killer cells
  • 2015
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 15:15, s. 3222-31
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate a simple method for three-dimensional (3D) cell culture controlled by ultrasonic standing waves in a multi-well microplate. The method gently arranges cells in a suspension into a single aggregate in each well of the microplate and, by this, nucleates 3D tissue-like cell growth for culture times between two and seven days. The microplate device is compatible with both high-resolution optical microscopy and maintenance in a standard cell incubator. The result is a scaffold- and coating-free method for 3D cell culture that can be used for controlling the cellular architecture, as well as the cellular and molecular composition of the microenvironment in and around the formed cell structures. We demonstrate the parallel production of one hundred synthetic 3D solid tumors comprising up to thousands of human hepatocellular carcinoma (HCC) HepG2 cells, we characterize the tumor structure by high-resolution optical microscopy, and we monitor the functional behavior of natural killer (NK) cells migrating, docking and interacting with the tumor model during culture. Our results show that the method can be used for determining the collective ability of a given number of NK cells to defeat a solid tumor having a certain size, shape and composition. The ultrasound-based method itself is generic and can meet any demand from applications where it is advantageous to monitor cell culture from production to analysis of 3D tissue or tumor models using microscopy in one single microplate device.
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36.
  • Comina, German, et al. (författare)
  • Low cost lab-on-a-chip prototyping with a consumer grade 3D printer
  • 2014
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 14:16, s. 2978-2982
  • Tidskriftsartikel (refereegranskat)abstract
    • Versatile prototyping of 3D printed lab-on-a-chip devices, supporting different forms of sample delivery, transport, functionalization and readout, is demonstrated with a consumer grade printer, which centralizes all critical fabrication tasks. Devices cost 0.57US$ and are demonstrated in chemical sensing and micromixing examples, which exploit established principles from reference technologies.
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37.
  • Comina, German, et al. (författare)
  • PDMS lab-on-a-chip fabrication using 3D printed templates
  • 2014
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 14:2, s. 424-430
  • Tidskriftsartikel (refereegranskat)abstract
    • The fabrication of conventional PDMS on glass lab-on-a-chip (LOC) devices, using templates printed with a commercial (2299 US$) micro-stereo lithography 3D printer, is demonstrated. Printed templates replace clean room and photolithographic fabrication resources and deliver resolutions of 50 mu m, and up to 10 mu m in localized hindrances, whereas the templates are smooth enough to allow direct transfer and proper sealing to glass substrates. 3D printed templates accommodate multiple thicknesses, from 50 mu m up to several mm within the same template, with no additional processing cost or effort. This capability is exploited to integrate silicone tubing easily, to improve micromixer performance and to produce multilevel fluidics with simple access to independent functional surfaces, which is illustrated by time-resolved glucose detection. The templates are reusable, can be fabricated in under 20 min, with an average cost of 0.48 US$, which promotes broader access to established LOC configurations with minimal fabrication requirements, relieves LOC fabrication from design skills and provides a versatile LOC development platform.
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38.
  • Corrie, S R, et al. (författare)
  • Surface-modified microprojection arrays for intradermal biomarker capture, with low non-specific protein binding
  • 2010
  • Ingår i: Lab on a Chip. - 1473-0197 .- 1473-0189. ; 10, s. 2655-2658
  • Tidskriftsartikel (refereegranskat)abstract
    • Minimally invasive biosensors are of great interest for rapid detection of disease biomarkers for diagnostic screening at the point-of-care. Here we introduce a device which extracts disease-specific biomarkers directly from the upper dermis, without the needle and syringe or resource-intensive blood processing. Using antigen-specific antibodies raised in mice as a model system, we confirm the analytical specificity and sensitivity of the antibody capture and extraction in comparison to the conventional methods based on needle/syringe blood draw followed by processing and antigen-specific ELISAs.
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39.
  • Cruz, Javier, 1990-, et al. (författare)
  • Inertial focusing with sub-micron resolution for separation of bacteria
  • 2019
  • Ingår i: Lab on a Chip. - : ROYAL SOC CHEMISTRY. - 1473-0197 .- 1473-0189. ; 19:7, s. 1257-1266
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we study inertial focusing in curved channels and demonstrate the alignment of particles with diameters between 0.5 and 2.0 m, a range of biological relevance since it comprises a multitude of bacteria and organelles of eukaryotic cells. The devices offer very sensitive control over the equilibrium positions and allow two modes of operation. In the first, particles having a large variation in size are focused and concentrated together. In the second, the distribution spreads in a range of sizes achieving separation with sub-micron resolution. These systems were validated with three bacteria species (Escherichia coli, Salmonella typhimurium and Klebsiella pneumoniae) showing good alignment while maintaining the viability in all cases. The experiments also revealed that the particles follow a helicoidal trajectory to reach the equilibrium positions, similar to the fluid streamlines simulated in COMSOL, implying that these positions occupy different heights in the cross section. When the equilibrium positions move to the inner wall as the flow rate increases, they are at a similar distance from the centre than in straight channels (approximate to 0.6R), but when the equilibrium positions move to the outer wall as the flow rate increases, they are closer to the centre and the particles pass close to the inner wall to elevate their position before reaching them. These observations were used along with COMSOL simulations to explain the mechanism behind the local force balance and the migration of particles, which we believe contributes to further understanding of the phenomenon. Hopefully, this will make designing more intuitive and reduce the high pressure demands, enabling manipulation of particles much smaller than a micrometer.
  •  
40.
  • Dalslet, Bjarke Thomas, et al. (författare)
  • Bead magnetorelaxometry with an on-chip magnetoresistive sensor
  • 2011
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 11:2, s. 296-302
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnetorelaxometry measurements on suspensions of magnetic beads are demonstrated using a planar Hall effect sensor chip embedded in a microfluidic system. The alternating magnetic field used for magnetizing the beads is provided by the sensor bias current and the complex magnetic susceptibility spectra are recorded as the 2nd harmonic of the sensor response. The complex magnetic susceptibility signal appears when a magnetic bead suspension is injected, it scales with the bead concentration, and it follows the Cole-Cole expression for Brownian relaxation. The complex magnetic susceptibility signal resembles that from conventional magnetorelaxometry done on the same samples apart from an offset in Brownian relaxation frequency. The time dependence of the signal can be rationalized as originating from sedimented beads.
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41.
  • Davidsson, Richard, et al. (författare)
  • Microfluidic biosensing systems - Part I. Development and optimisation of enzymatic chemiluminescent mu-biosensors based on silicon microchips
  • 2004
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189. ; 4:5, s. 481-487
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemiluminescent (CL) enzyme-based flow-through microchip biosensors (mu-biosensors) for detection of glucose and ethanol were developed for the purpose of monitoring real-time production and release of glucose and ethanol from microchip immobilised yeast cells. Part I of this study focuses on the development and optimisation of the mu-biosensors in a microfluidic sequential injection analysis (muSIA) system. Glucose oxidase (GOX) or alcohol oxidase (AOX) was co-immobilised with horseradish peroxidase (HRP) on porous silicon flow through microchips. The hydrogen peroxide ;produced from oxidation of the corresponding analyte (glucose or ethanol) took part in the chemiluminescent (CL) oxidation of luminol catalysed by HRP enhanced by addition of p-iodophenol ( PIP). All steps in the mSIA system, including control of syringe pump, multiposition valve (MPV) and data readout, were computer controlled. The influence of flow rate and luminol- and PIP concentration were investigated using a 2(3)-factor experiment using the GOX-HRP sensor. It was found that all estimated single factors and the highest order of interaction were significant. The optimum was found at 250 muM luminol and 150 muM PIP at a flow rate of 18 mul min(-1), the latter as a compromise between signal intensity and analysis time. Using the optimised system settings one sample was processed within 5 min. Two different immobilisation chemistries were investigated for both m-biosensors based on 3-aminopropyltriethoxsilane (APTS)- or polyethylenimine (PEI) functionalisation followed by glutaraldehyde (GA) activation. GOX-HRP mu-biosensors responded linear in a log-log format within the range 10-1000 mM glucose. Both had an operational stability of at least 8 days, but the PEI-GOX-HRP sensor was more sensitive. The AOX-HRP mu-biosensors responded linear (log-log) in the range between 1 and 10 mM ethanol, but the PEI-AOX-HRP sensor was in general more sensitive. Both sensors had an operational stability of at least 8 h, but with a half-life of 2-3 days.
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42.
  • Davidsson, Richard, et al. (författare)
  • Microfluidic biosensing systems - Part II. Monitoring the dynamic production of glucose and ethanol from microchip-immobilised yeast cells using enzymatic chemiluminescent mu-biosensors
  • 2004
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189. ; 4:5, s. 488-494
  • Tidskriftsartikel (refereegranskat)abstract
    • A microfluidic flow injection (muFIA) system was employed for handling and monitoring of cell-released products from living cells immobilised on silicon microchips. The dynamic release of glucose and ethanol produced from sucrose by immobilised Saccharomyces cerevisiae cells was determined using microchip biosensors (mu-biosensors) with either co-immobilised glucose oxidase-horseradish peroxidase (GOX-HRP), or alcohol oxidase-horseradish peroxidase (AOX-HRP), catalysing a series of reactions ending up with chemiluminescence (CL) generated from HRP-catalysed oxidation of luminol in presence of p-iodophenol (PIP). The yeast cells were attached by first treating them with polyethylenimine (PEI) followed by adsorption to the microchip surface. The cell loss during assaying was evaluated qualitatively using scanning electron microscopy (SEM), showing that no cells were lost after 35 min liquid handling of the cell chip at 10 mul min(-1). The enzymes were immobilised on microchips via PEI-treatment followed by glutaraldehyde (GA) activation. The GOX-HRP mu-biosensors could be used during five days without any noticeable decrease in response, while the AOX-HRP mu-biosensors showed continuously decreasing activity, but could still be used employing calibration correction. The glucose and ethanol released from the immobilised yeast chips were quantitatively monitored, by varying the incubation time with sucrose, showing the possibilities and advantages of using a microfluidic system set-up for cell-based assays.
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43.
  • Deshmukh, Sameer, et al. (författare)
  • Acoustic radiation forces at liquid interfaces impact the performance of acoustophoresis.
  • 2014
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189. ; 14:17, s. 3394-3400
  • Tidskriftsartikel (refereegranskat)abstract
    • Acoustophoresis is a method well suited for cell and microbead separation or concentration for downstream analysis in microfluidic settings. One of the main limitations that acoustophoresis share with other microfluidic techniques is that the separation efficiency is poor for particle-rich suspensions. We report that flow laminated liquids can be relocated in a microchannel when exposed to a resonant acoustic field. Differences in acoustic impedance between two liquids cause migration of the high-impedance liquid towards an acoustic pressure node. In a set of experiments we charted this phenomenon and show herein that it can be used to either relocate liquids with respect to each other, or to stabilize the interface between them. This resulted in decreased medium carry-over when transferring microbeads (4% by volume) between suspending liquids using acoustophoresis. Furthermore we demonstrate that acoustic relocation of liquids occurs for impedance differences as low as 0.1%.
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44.
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45.
  • Douagi, Anna Sjöström, et al. (författare)
  • Young researchers to tackle future Grand Challenges
  • 2012
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 12:4, s. 680-683
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
46.
  • Enger, Jonas, 1966, et al. (författare)
  • Optical tweezers applied to a microfluidic system
  • 2004
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 4, s. 196-200
  • Tidskriftsartikel (refereegranskat)abstract
    • We will demonstrate how optical tweezers can be combined with a microfluidic system to create a versatile microlaboratory. Cells are moved between reservoirs filled with different media by means of optical tweezers. We show that the cells, on a timescale of a few seconds, can be moved from one reservoir to another without the media being dragged along with them. The system is demonstrated with an experiment where we expose E. coli bacteria to different fluorescent markers. We will also discuss how the system can be used as an advanced cell sorter. It can favorably be used to sort out a small fraction of cells from a large population, in particular when advanced microscopic techniques are required to distinguish various cells. Patterns of channels and reservoirs were generated in a computer and transferred to a mask using either a sophisticated electron beam technique or a standard laser printer. Lithographic methods were applied to create microchannels in rubber silicon (PDMS). Media were transported in the channels using electroosmotic flow. The optical system consisted of a combined confocal and epi-fluorescence microscope, dual optical tweezers and a laser scalpel.
  •  
47.
  • Eriksson, Emma, 1980, et al. (författare)
  • A microfluidic device for reversible environmental changes around single cells using optical tweezers for cell selection and positioning
  • 2010
  • Ingår i: Lab Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 10:5, s. 617-625
  • Tidskriftsartikel (refereegranskat)abstract
    • Cells naturally exist in a dynamic chemical environment, and therefore it is necessary to study cell behaviour under dynamic stimulation conditions in order to understand the signalling transduction pathways regulating the cellular response. However, until recently, experiments looking at the cellular response to chemical stimuli have mainly been performed by adding a stress substance to a population of cells and thus only varying the magnitude of the stress. In this paper we demonstrate an experimental method enabling acquisition of data on the behaviour of single cells upon reversible environmental perturbations, where microfluidics is combined with optical tweezers and fluorescence microscopy. The cells are individually selected and positioned in the measurement region on the bottom surface of the microfluidic device using optical tweezers. The optical tweezers thus enable precise control of the cell density as well as the total number of cells within the measurement region. Consequently, the number of cells in each experiment can be optimized while clusters of cells, that render subsequent image analysis more difficult, can be avoided. The microfluidic device is modelled and demonstrated to enable reliable changes between two different media in less than 2 s. The experimental method is tested by following the cycling of GFP-tagged proteins (Mig1 and Msn2, respectively) between the cytosol and the nucleus in Saccharomyces cerevisiae upon changes in glucose availability.
  •  
48.
  • Eriksson, Emma, 1980, et al. (författare)
  • A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes
  • 2007
  • Ingår i: Lab on a chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 7:1, s. 71-76
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the development of an experimental platform where epi-fluorescence microscopy and optical tweezers are combined with a microfluidic system to enable the analysis of rapid cytological responses in single cells. The microfluidic system allows two different media to be merged in a Y-shaped channel. Microscale channel dimensions ensure purely laminar flow and, as a result, an environmental gradient can be created between the two media. Optical tweezers are used to move a single trapped cell repeatedly between the different environments. The cell is monitored continuously by fluorescence microscopy during the experiment. In a first experiment on yeast (Saccharomyces cerevisiae) we observed changes in cell volume as the cell was moved between environments with different osmolarity. This demonstrated that the platform allowed analysis of cytological alterations on a time scale shorter than 0.2 s. In a second experiment we observed the spatial migration of the Yap1p transcription factor fused to GFP as a cell was moved from an environment of low to high oxidative capacity. The system is universal allowing the response to numerous environmental changes to be studied on the sub second time scale in a variety of model cells. We intend to use the platform to study how the age of cells, their progression through the cell cycle, or their genetic landscape, alter their capacity (kinetics and amplitude) to respond to environmental changes.
  •  
49.
  • Evander, Mikael, et al. (författare)
  • Acoustofluidics 20: Applications in acoustic trapping.
  • 2012
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 12:22, s. 4667-4676
  • Tidskriftsartikel (refereegranskat)abstract
    • This part of the Acoustofluidics tutorial series reviews applications in acoustic trapping of micron-sized particles and cells in microfluidic systems. Acoustic trapping enables non-invasive and non-contact immobilisation of cells and particles in microfluidic systems. Acoustic trapping has been used for reducing the time needed to create 3D cell clusters, enhance particle-based bioassays and facilitated interaction studies of both cells and particles. An area that is increasingly interesting is the use of acoustic trapping for enriching low concentration samples and the washing or fractioning of cell populations prior to sensitive detection methods (MALDI-MS, PCR etc.) The main focus of the review is systems where particles can be retained against a flow while applications in which particles are positioned in a stationary fluid will be addressed in part 21 of the Acoustofluidics tutorial series (M. Wiklund, S. Radel and J. J. Hawkes, Lab Chip, 2012, 12, ).
  •  
50.
  • Evander, Mikael, et al. (författare)
  • Microfluidic impedance cytometer for platelet analysis.
  • 2013
  • Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 13:4, s. 722-729
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the design and performance characteristics of a platelet analysis platform based on a microfluidic impedance cytometer. Dielectrophoretic focusing is used to centre cells in a fluid stream, which then forms the core of a two-phase flow (dielectric focusing). This flow then passes between electrodes for analysis by differential impedance spectroscopy at multiple frequencies from 280 kHz to 4 MHz. This approach increases the signal-to-noise ratio relative to a single-phase, unfocused stream, while minimising the shear forces to which the cells are subjected. The percentage of activated platelets before and after passage through the chip was measured using flow cytometry, and no significant change was measured. Measuring the in-phase amplitude at a single frequency is sufficient to distinguish platelets from erythrocytes. Using multi-frequency impedance measurements and discriminant analysis, resting platelets can be discriminated from activated platelets. This multifrequency impedance cytometer therefore allows ready determination of the degree of platelet activation in blood samples.
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