| 1. |
- Olofsson, Jessica, 1975, et al.
(författare)
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A chemical waveform synthesizer
- 2005
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Ingår i: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 102:23, s. 8097-8102
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Tidskriftsartikel (refereegranskat)abstract
- Algorithms and methods were developed to synthesize complex chemical waveforms in open volumes by using a scanning-probe microfluidic platform. Time-dependent variations and oscillations of one or several chemical species around the scanning probe, such as formation of sine waves, damped oscillations, and generation of more complex patterns, are demonstrated. Furthermore, we show that intricate bursting and chaotic calcium oscillations found in biological microdomains can be reproduced and that a biological cell can be used as a probe to study receptor functionalities as a function of exposure to time-dependent variations of receptor activators and inhibitors. Thus, the method allows for studies of biologically important oscillatory reactions. More generally, the system allows for detailed studies of complex time-varying chemical and physical phenomena in solution or at solution/surface interfaces.
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| 2. |
- Olofsson, Jessica, 1975, et al.
(författare)
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A microfluidics approach to the problem of creating separate solution environments accessible from macroscopic volumes
- 2004
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 76:17, s. 4968-4976
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Tidskriftsartikel (refereegranskat)abstract
- We report on a microfluidic device that generates separate solution environments in macroscopic volumes. Spatially distinct patterns are created by emitting fluids from 16 different sources (closely spaced microchannels) into a solution-filled macroscopic chamber. The fluid in neighboring microchannels couples viscously in the macroscopic container, generating one single interdigitated stream. Scanning nanoelectrode amperometry was used for characterizing the concentration landscape and the diffusion zones between solutions running in parallel at different coordinates in the stream. These experiments were complemented by finite element simulations of the Navier-Stokes and mass transport equations to describe the velocity distributions and the diffusion behavior. For in channel flow velocities of 50 mm·s -1 , patterns could persist on the order of millimeters to centimeters in the open volume. The most narrow diffusion zones with widths less than 10 μm (5-95% concentration change) were found some tens of micrometers out in the macroscopic container. We demonstrate that a 14-μm-diameter nearly spherical object (biological cell) attached to a micropipet can be moved from one solution environment to another by a lateral displacement of only 8 μm. The device is suitable for applications where the solution environment around a microscopic or nanoscopic sensor needs to be changed multiple times, i.e., in order to build layered structures, for obtaining binding isotherms, and kinetic information, for example, on ion channels, enzymes, and receptors as well as in applications where different loci on an object need to be exposed to different environments or where complex solution environments need to be created for studies of interfacial chemistry between two streaming layers.
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| 3. |
- Pihl, Johan, 1975, et al.
(författare)
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Microfluidic gradient-generating device for pharmacological profiling
- 2005
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:13, s. 3897-3903
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Tidskriftsartikel (refereegranskat)abstract
- We describe an on-chip microfluidic gradient-generating device that generates concentration gradients spanning nearly 5 orders of magnitude starting from a single concentration. The exiting stream of drugs held at different concentrations remains laminar in a recording chamber and can be presented as 24 discrete solutions to a cell-based sensor. The high-performance characteristics of the device are demonstrated by pharmacological screening of voltage-gated K + channels (hERG) and ligand-gated GABAA receptors using scanning-probe patch-clamp measurements. Multiple data point dose-response curves and IC 50 and EC 50 values were rapidly obtained, typically in less than 30 min, through its combined functionality of gradient generation and open-volume laminar flow. The device facilitates rapid pharmacological profiling of ion channel and GPCR effectors and enables the acquisition of large numbers of data points with minute sample consumption and handling. © 2005 American Chemical Society.
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| 4. |
- Wright, Jack, et al.
(författare)
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The crystal structure of PD1, a Haemophilus surface fibril domain
- 2017
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Ingår i: Acta crystallographica. Section F, Structural biology communications. - 2053-230X. ; 73:2, s. 101-108
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Tidskriftsartikel (refereegranskat)abstract
- The Haemophilus surface fibril (Hsf) is an unusually large trimeric autotransporter adhesin (TAA) expressed by the most virulent strains of H. influenzae. Hsf is known to mediate adhesion between pathogen and host, allowing the establishment of potentially deadly diseases such as epiglottitis, meningitis and pneumonia. While recent research has suggested that this TAA might adopt a novel 'hairpin like' architecture, the characterization of Hsf has been limited to in silico modelling and electron micrographs, with no high resolution structural data available. Here, the crystal structure of Hsf putative domain 1 (PD1) is reported at 3.3 Å resolution. The structure corrects the previous domain annotation by revealing the presence of an unexpected N terminal TrpRing domain. PD1 represents the first Hsf domain to be solved, and thus paves the way for further research on the 'hairpin like' hypothesis.
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