| 1. |
- Beech, Jason P., et al.
(author)
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Active Posts in Deterministic Lateral Displacement Devices
- 2019
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In: Advanced Materials Technologies. - : Wiley. - 2365-709X. ; 4:9
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Journal article (peer-reviewed)abstract
- Using electrically connected metal-coated posts in a deterministic lateral displacement (DLD) device and applying electric fields, electrokinetics is used to tune separations, significantly decrease the critical size for separation, and increase the dynamic range with switching times on the order of seconds. The strength of DLD stems from its binary behavior. To first approximation, particles move in one out of two trajectories based on their effective size. For particles that are close to the threshold size, a small external force is sufficient to nudge the particles from one trajectory to another. The devices consist of arrays of cylindrical metal-coated SU-8 posts connected by an underlying metal layer. This allows the application of voltages at the post surfaces and the generation of electric field gradients between neighboring posts, causing polarizable particles to experience a dielectrophoretic (DEP) force. This force, which depends on the volume and polarizability of the particle, can be made sufficient to push particles from one trajectory into another. In this way, the critical size in a device, normally fixed by the geometry, can be tuned. What's more, adding DEP in this way allows for the simultaneous creation of multiple size fractions.
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| 2. |
- Beech, Jason P., et al.
(author)
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Electrokinetic wall effect mechanisms and applications
- 2020
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In: MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9781733419017 ; , s. 42-43
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Conference paper (peer-reviewed)abstract
- Under the application of longitudinal electric fields in microchannels, microparticles experience lift forces that push them away from the channel walls and affect their trajectories. At high frequencies (>100KHz) the dielectrophoretic forces dominate and are well understood but at lower frequencies there is little agreement as to the exact nature of the forces, how they are generated and how they vary due to the many different experimental conditions that are used in microfluidics devices. Here we present an experimental study of these mechanisms.
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| 3. |
- Beech, Jason P., et al.
(author)
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Separation of pathogenic bacteria by chain length
- 2018
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In: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 1000, s. 223-231
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Journal article (peer-reviewed)abstract
- Using Deterministic Lateral Displacement devices optimized for sensitivity to particle length, we separate subpopulations of bacteria depending on known properties that affect their capability to cause disease (virulence). For the human bacterial pathogen Streptococcus pneumoniae, bacterial chain length and the presence of a capsule are known virulence factors contributing to its ability to cause severe disease. Separation of cultured pneumococci into subpopulations based on morphological type (single cocci, diplococci and chains) will enable more detailed studies of the role they play in virulence. Moreover, we present separation of mixed populations of almost genetically identical encapsulated and non-encapsulated pneumococcal strains in our device.
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| 4. |
- Beech, Jason P., et al.
(author)
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Sorting bacteria by chain length - A factor of virulence?
- 2016
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In: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016. - 9780979806490 ; , s. 250-251
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Conference paper (peer-reviewed)abstract
- Using Deterministic Lateral Displacement (DLD), we are able to separate bacteria by their size and their chain length. This separation enables the study of these properties as factors of virulence.
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| 5. |
- Beech, Jason P., et al.
(author)
-
The separation of nano-sized particles in micro-scaled post arrays
- 2019
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In: 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019. - 9781733419000 ; , s. 10-11
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Conference paper (peer-reviewed)abstract
- The precise separation of nanoscale particles has proven challenging due to diffusion and the need to use nanoscale devices. We show the separation of particles in the 100 nm size range in Deterministic Lateral Displacement (DLD) devices with feature sizes in the 10 µm size range. We achieve this using Dielectrophoretic (DEP) forces, generated between the metal coated posts that act as active electrodes. This opens up for the separation of submicron particles based not only on size but also on electric and dielectric properties.
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| 6. |
- Beech, Jason P., et al.
(author)
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Tunable separation and DNA manipulation in metal coated pillar arrays
- 2018
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In: 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018. - 9781510897571 ; 4, s. 2090-2093
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Conference paper (peer-reviewed)abstract
- Implementing electrically connected metal-coated posts in a Deterministic Lateral Displacement (DLD) device and applying electric fields, we use electrokinetics to achieve tunable particle separations and to trap and manipulate DNA. The strength of DLD stems from its typically binary behavior. Particles move in one out of two trajectories based on their effective size. For particles that are close to the threshold size, a minute external force is sufficient to nudge the particles from one trajectory to another. Dielectrophoresis (DEP) provides such a force and also gives specificity based on the dielectric properties of the particles.
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| 7. |
- Ho, Bao Dang
(author)
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Cell Sorting in Pillar Arrays based on Electrokinetics and Morphology
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Deterministic Lateral Displacement (DLD) is a method capable of sorting cells based on size where mechanicalinteractions between a sufficiently large particle and obstacles in a microfludic pillar array force the particle tofollow a different trajectory than their smaller counterparts, resulting in continuous lateral separation. To extendthe capability of DLD, electrical interaction between particles and pillars can be employed to complement themechanical interaction, making electrical/dielectric properties additional parameters for sorting. Another idea isto exploit the morphologies of cells and as a concequence, their dynamical properties, to sort them in DLD. Thedevelopment of DLD cell sorting methods based on those two ideas has brought forth five papers appended to thisthesis: paper I, III, and V (combination of electrokinetics and DLD), and paper II and IV (exploiting morphologyin sorting by DLD).In the first topic, differences in electric properties or dielectric properties of particles and cells are employed toextend the capability of DLD. In Paper I, an AC electric field was applied across DLD devices having insulatingpillars to sort similar-sized polystyrene particles having different surface charge, viable from non-viable yeast cells,and viable from non-viable E. coli bacteria. In Paper III, the same method was utilised on open channel DLDdevices, showing unaltered effectiveness but offering the ability to flexibly change the distance between the electrodes.Also in the topic of combining electrokinetics and DLD, Paper V introduced a new type of DLD devicewhere the electrodes were defined locally on every pillar, making it easier to generate a high electric field strength.Besides electrical properties, morphology is another useful accompaniment to DLD. In Paper II, pathogenicStreptococcus pneumoniae bacteria were fractionated in DLD devices according to the difference in their morphology,viz. their chain length. It was also demonstrated, in paper IV, that an AC field can be used to rotatenon-spherical red blood cells and in turn, change their trajectory in a DLD device. This implies an opportunity tosort red blood cells from cells having different morphology, either spherical cells or parasites like trypanosomes.
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| 8. |
- Kim, Rebekah, et al.
(author)
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DNA sample cleanup using deterministic lateral displacement
- 2016
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In: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016. - 9780979806490 ; , s. 1527-1528
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Conference paper (peer-reviewed)abstract
- Optical mapping relies on the preparation of fluorescent DNA. DNA must be imaged with good signal to noise and therefore the background of unwanted DNA fragments, fluorescent dyes and other reagents need to be removed. We use deterministic lateral displacement to separate 48.5 kbp DNA from < 10 kbp DNA. We also show the removal of 48.5 kbp DNA fragments from a background of fluorescent ATTO647N molecules and the recovery of >50 kbp molecules from a background of shorter digested fragments. In both cases improving signal to noise during imaging.
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| 9. |
- Lozano, Rafael, et al.
(author)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Journal article (peer-reviewed)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 10. |
- Tran, Si Hoai Trung, et al.
(author)
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Sorting breast cancer cells based on deformability
- 2015
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In: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9780979806483 ; , s. 364-366
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Conference paper (peer-reviewed)abstract
- Due to their direct coupling to the physiology of the cells, the physical properties are especially attractive as markers for sorting and characterization of cancer cells. Where molecular surface markers are lacking, the physical properties can instead serve as inherent markers for separation. This is especially interesting for cancer cells where there are indications that soft cells are more metastatic than hard cells. Our work is expected to provide a deeper understanding of deformability based sorting based on deterministic lateral displacement (DLD). This will subsequently be used to optimize DLD devices for characterization and fractionation of cancer cells into subpopulations of different mechanical properties. Our aim is to develop a device to help oncologists gain more accurate prognoses and better monitoring of the effect of treatment.
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