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- Beech, Jason P, et al.
(author)
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Using symmetry to control viscoelastic waves in pillar arrays
- 2023
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In: RSC Advances. - 2046-2069. ; 13:45, s. 31497-31506
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Journal article (peer-reviewed)abstract
- Solutions of macromolecules exhibit viscoelastic properties and unlike Newtonian fluids, they may break time-reversal symmetry at low Reynolds numbers resulting in elastic turbulence. Furthermore, under some conditions, instead of the chaotic turbulence, the result is large-scale waves in the form of cyclic spatial and temporal concentration variations, as has been shown for macromolecular DNA flowing in microfluidic pillar arrays. We here demonstrate how altering the symmetry of the individual pillars can be used to influence the symmetry of these waves. We control the extent of instabilities in viscoelastic flow by leveraging the effects of the symmetry of the pillars on the waves, demonstrating suppressed viscoelastic fluctuations with relevance for transport and sorting applications, or conversely opening up for enhanced viscoelasticity-mediated mixing. The onset of waves, which changes flow resistance, occurs at different Deborah numbers for flow in different directions through the array of triangular pillars, thus breaking the symmetry of the flow resistance along the device, opening up for using the occurrence of the waves to construct a fluidic diode.
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- Krog, Jens, et al.
(author)
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Photophysical image analysis : Unsupervised probabilistic thresholding for images from electron-multiplying charge-coupled devices
- 2024
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In: PLoS ONE. - 1932-6203. ; 19:4, s. 0300122-0300122
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Journal article (peer-reviewed)abstract
- We introduce the concept photophysical image analysis (PIA) and an associated pipeline for unsupervised probabilistic image thresholding for images recorded by electron-multiplying charge-coupled device (EMCCD) cameras. We base our approach on a closed-form analytic expression for the characteristic function (Fourier-transform of the probability mass function) for the image counts recorded in an EMCCD camera, which takes into account both stochasticity in the arrival of photons at the imaging camera and subsequent noise induced by the detection system of the camera. The only assumption in our method is that the background photon arrival to the imaging system is described by a stationary Poisson process (we make no assumption about the photon statistics for the signal). We estimate the background photon statistics parameter, λbg, from an image which contains both background and signal pixels by use of a novel truncated fit procedure with an automatically determined image count threshold. Prior to this, the camera noise model parameters are estimated using a calibration step. Utilizing the estimates for the camera parameters and λbg, we then introduce a probabilistic thresholding method, where, for the first time, the fraction of misclassified pixels can be determined a priori for a general image in an unsupervised way. We use synthetic images to validate our a priori estimates and to benchmark against the Otsu method, which is a popular unsupervised non-probabilistic image thresholding method (no a priori estimates for the error rates are provided). For completeness, we lastly present a simple heuristic general-purpose segmentation method based on the thresholding results, which we apply to segmentation of synthetic images and experimental images of fluorescent beads and lung cell nuclei. Our publicly available software opens up for fully automated, unsupervised, probabilistic photophysical image analysis.
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- Lauppe, Rosa, et al.
(author)
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Differing impact of clinical factors on the risk of fracture in younger and older women in the general population and an osteoporosis clinic population
- 2019
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In: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 14:1
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Journal article (peer-reviewed)abstract
- Summary: This study assesses the impact of risk factors for fracture in women aged 80+ and 60–79. The results suggest that risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort. Purpose: This study assesses whether the impact of classical risk factors for fracture due to osteoporosis is different in women aged 80+ and women aged 60–79. Since most prior research on the contribution of risk factors is based on patients below 80 years of age, this study aims to fill this knowledge gap to increase the accuracy of risk assessment in the oldest old. Methods: Retrospective, observational cohort study using Swedish national health register data and BMD data from osteoporosis clinics. Women aged at least 60 were identified from a random sample of the general population and from the BMD databases and allocated to two populations representing patients at different stages of risk assessment. The relative impact of risk factors on fracture risk was assessed using multivariate competing risk regression with fracture as outcome and death as competing event. Results: A total of 163,329 women were included from the general population (52,499 aged 80+) and 22,378 from the BMD databases (4563 aged 80+). The clinical risk factors with relatively highest effect on fracture risk in the older patients were prior fracture and hip T-score below − 2.5 SD. Other included risk factors showed lower impact in the older compared to the younger strata. Conclusions: This study confirms our understanding of the key risk factors for fracture: age, prior fracture, and a low T-score. Regarding remaining risk factors, risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort.
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- Ström, Oskar E., et al.
(author)
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DNA concentration wave formation in pillar arrays
- 2020
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In: MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9781733419017 ; , s. 240-241
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Conference paper (peer-reviewed)abstract
- High throughput in particle and molecular sorting schemes is an important performance indicator and can be realized through increased volumetric processing rates or increased concentrations. Here we investigate the effect of increased concentration of high-molecular weight DNA in micropillar arrays for deterministic lateral displacement (DLD). We find that the array imposes regular fluctuations in the concentration of the DNA if the sample concentration and flow rates exceed respective threshold values. We characterize the resulting concentration waves and study their influence on microsphere trajectories in the device. We expect our results to be relevant e.g. for sample preparation of cell lysates which can often be complicated by the release of chromosomal DNA.
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| 8. |
- Ström, Oskar E., et al.
(author)
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Geometry-Dependent Elastic Flow Dynamics in Micropillar Arrays
- 2024
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In: Micromachines. - 2072-666X. ; 15:2
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Journal article (peer-reviewed)abstract
- Regular device-scale DNA waves for high DNA concentrations and flow velocities have been shown to emerge in quadratic micropillar arrays with potentially strong relevance for a wide range of microfluidic applications. Hexagonal arrays constitute another geometry that is especially relevant for the microfluidic pulsed-field separation of DNA. Here, we report on the differences at the micro and macroscopic scales between the resulting wave patterns for these two regular array geometries and one disordered array geometry. In contrast to the large-scale regular waves visible in the quadratic array, in the hexagonal arrays, waves occur in a device-scale disordered zig-zag pattern with fluctuations on a much smaller scale. We connect the large-scale pattern to the microscopic flow and observe flow synchronization that switches between two directions for both the quadratic and hexagonal arrays. We show the importance of order using the disordered array, where steady-state stationary and highly fluctuating flow states persist in seemingly random locations across the array. We compare the flow dynamics of the arrays to that in a device with sparsely distributed pillars. Here, we observe similar vortex shedding, which is clearly observable in the quadratic and disordered arrays. However, the shedding of these vortices couples only in the flow direction and not laterally as in the dense, ordered arrays. We believe that our findings will contribute to the understanding of elastic flow dynamics in pillar arrays, helping us elucidate the fundamental principles of non-Newtonian fluid flow in complex environments as well as supporting applications in engineering involving e.g., transport, sorting, and mixing of complex fluids.
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| 9. |
- Ström, Oskar E., et al.
(author)
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High-Throughput Separation of Long DNA in Deterministic Lateral Displacement Arrays
- 2022
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In: Micromachines. - : MDPI AG. - 2072-666X. ; 13:10
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Journal article (peer-reviewed)abstract
- Length-based separation of DNA remains as relevant today as when gel electrophoresis was introduced almost 100 years ago. While new, long-read genomics technologies have revolutionised accessibility to powerful genomic data, the preparation of samples has not proceeded at the same pace, with sample preparation often constituting a considerable bottleneck, both in time and difficulty. Microfluidics holds great potential for automated, sample-to-answer analysis via the integration of preparatory and analytical steps, but for this to be fully realised, more versatile, powerful and integrable unit operations, such as separation, are essential. We demonstrate the displacement and separation of DNA with a throughput that is one to five orders of magnitude greater than other microfluidic techniques. Using a device with a small footprint (23 mm × 0.5 mm), and with feature sizes in the micrometre range, it is considerably easier to fabricate than parallelized nano-array-based approaches. We show the separation of 48.5 kbp and 166 kbp DNA strands achieving a significantly improved throughput of 760 ng/h, compared to previous work and the separation of low concentrations of 48.5 kbp DNA molecules from a massive background of sub 10 kbp fragments. We show that the extension of DNA molecules at high flow velocities, generally believed to make the length-based separation of long DNA difficult, does not place the ultimate limitation on our method. Instead, we explore the effects of polymer rotations and intermolecular interactions at extremely high DNA concentrations and postulate that these may have both negative and positive influences on the separation depending on the detailed experimental conditions.
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| 10. |
- Ström, Oskar E., et al.
(author)
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Integrated on-chip system for DNA purification, labelling and surface stretching
- 2018
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In: 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018. - 9781510897571 ; 2, s. 1177-1180
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Conference paper (peer-reviewed)abstract
- We report a simplified, integrated and more efficient way of preparing DNA for analysis. We have developed a microfluidic platform that can purify DNA and subsequently label and stretch it on a surface. We have successfully extracted DNA from a gel-filled microfluidic channel using electrophoresis and subsequently stretched the DNA linearly by absorption to either a hydrophobic or a positively-charged surface. To our knowledge, DNA has not previously been stretched on to a surface while being moved using an electric field in this way. We have also labelled DNA after stretching with intercalating dyes. The intention, following stretching and labelling, is to analyze the DNA with optical mapping.
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