| 1. |
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| 2. |
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| 3. |
- Bodén, Roger, et al.
(författare)
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Microdispenser with continuous flow and selectable target volume for microfluidic high-pressure applications
- 2014
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 23:2, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a reusable microdispenser intended for continuous flow dispensing of variable and controlled volumes of liquid against high back-pressures. The microdispenser consists of two active valves and a dispenser chamber, all actuated by the volume change associated with the solid-to-liquid phase transition of paraffin wax. It is fabricated using stainless steel sheets, a flexible printed circuit board, and a polyimide membrane. All are covered with Parylene C for insulation and fusion bonding at assembly. A finite element method (FEM) model of the paraffin actuator is used to predict the resulting flow characteristics. The results show dispensing of well-defined volumes of 350 and 540 nL, with a good repeatability between dispensing sequences, as well as reproducibility between devices. In addition, the flow characteristics show no back-pressure dependence of the dispensed flow in the interval 0.5--2.0 MPa. The FEM model can be used to predict the flow characteristics qualitatively
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| 4. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
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| 6. |
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| 7. |
- Jonsson, Jonas, et al.
(författare)
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Acoustically enriching, large-depth aquatic sampler
- 2012
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Ingår i: Lab on a Chip. - 1473-0197 .- 1473-0189. ; 12:9, s. 1619-1628
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Tidskriftsartikel (refereegranskat)abstract
- In marine biology, it is useful to collect water samples when exploring the distribution and diversity of microbial communities in underwater environments. In order to provide, e.g., a miniaturized submersible explorer with the capability of collecting microorganisms, a compact sample enrichment system has been developed. The sampler is 30 mm long, 15 mm wide, and just a few millimetres thick. Integrated in a multilayer steel, polyimide and glass construction is a microfluidic channel with piezoelectric transducers, where microorganism and particle samples are collected and enriched, using acoustic radiation forces for gentle and labelless trapping. High-pressure, latchable valves, using paraffin as the actuation material, at each end of the microfluidic channel keep the collected sample pristine. A funnel structure raised above the surface of the device directs water into the microfluidic channel as the vehicle propels itself or when there is a flow across its hull. The valves proved leak proof to a pressure of 2.1 MPa for 19 hours and momentary pressures of 12.5 MPa, corresponding to an ocean depth of more than 1200 metres. By reactivating the latching mechanism, small leakages through the valves could be remedied, which could thus increase the leak-less operational time. Fluorescent particles, 1.9 µm in diameter, were successfully trapped in the microfluidic channel at flow rates up to 15 ml min-1, corresponding to an 18.5 cm s-1 external flow rate of the sampler. In addition, liquid-suspended GFP-marked yeast cells were successfully trapped.
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| 8. |
- Jonsson, Jonas, et al.
(författare)
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Instrumentation and vehicle platform of a miniaturized submersible for exploration of terrestrial and extraterrestrial aqueous environments
- 2012
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Ingår i: Acta Astronautica. - : Elsevier BV. - 0094-5765 .- 1879-2030. ; 79, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- An example of an extraterrestrial environment likely to support life is the vast liquid body believed to hide underneath the frozen crust of Jupiter's moon Europa. The hypothetical exploration of this, as well as the more accessible subglacial lakes on Earth, has been used as model applications for the development of a heavily miniaturized, yet qualified, submersible with the potential to be deployable either in itself through a long and narrow borehole or as the daughter craft of an ice-penetrating cryobot.Onboard the submersible, which is only 20 cm in length and 5 cm in diameter, accommodation of a versatile set of sensors and instruments capable of characterizing and imaging the surroundings, and even collecting water samples with microorganisms for return, is facilitated through the use of miniaturization technologies. For instance, together with a small camera, a laser-based, microoptic device enables the 3-D reconstruction of imaged objects for topographical measurements. As a complement, when the water is turbid or a longer range is wanted, the world's smallest side-scanning sonar, exhibiting centimeter resolution and a range of over 30 m, has been developed. The work on miniaturizing a CTD, which is a widely employed oceanographic instrument used to measure and correlate conductivity, temperature, and depth, has commenced. Furthermore, a device employing acoustics to trap microscopic particles and organisms, and, by this, enrich water samples, is under development. To ensure that the gathered samples are pristine until analyzed at the end of a mission, the device is equipped with high-pressure, latchable valves.Remote operation and transfer of measurement data and images, or even live streaming of video, is made possible through a kilometer-long fiber optic cable being reeled out from the vehicle underway and tethering it to a terminal. To extend the missions, the same fiber shall also be capable of charging the onboard batteries.In this paper, the vehicle and its subsystems are summarized. Subsystems essential for the vehicle's operation, e.g., hull structure, communication and power management, are treated separately from those of more mission-specific nature, like the instruments mentioned above.
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| 9. |
- Jonsson, Jonas, et al.
(författare)
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Miniaturized submersible for exploration of aqueous environments on Earth and beyond
- 2011
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Konferensbidrag (refereegranskat)abstract
- Some of the most likely environments to support extraterrestrial life in our solar system are the ice-covered moons, suchas Europa, thought to harbor a liquid ocean underneath its frozen crust. Exploration, however, necessitates an ice-penetratingcryobot, or a long and narrow borehole, and the subsequent deployment of a small submersible, a hydrobot, with severe sizerestrictions imposed on its scientific payload. As a stepping stone for exploration of such environments, a small instrumentladenedsubmersible vehicle is currently under development.Employment of a large set of instruments capable of characterizing the aqueous environment, imaging the surroundingsand collecting microorganisms is essential for the determination of habitability. Despite the submersible being only 20 cm inlength and 5 cm in diameter, a high degree of functionality is facilitated here through the use of miniaturization technologies. Forinstance, a compact laser-illuminated diffractive optical element, paired with a high-resolution camera, enable photogrammetryand the reconstruction of objects’ shapes in 3-D space. Also for imaging, the world’s smallest side-scanning sonar has beendeveloped to acoustically image, either where water is too turbid for the camera, or where longer range is necessary. Currently,the sonar exhibits centimeter resolution and ranges over 30 meters. On the sensor side, a most vital oceanographic instrument, theCTD, used to measure the conductivity, temperature, and depth of water, has been heavily miniaturized and preliminaryevaluated. Additionally, a water sampler combining integrated selection and enriching capabilities to filter out and accommodate,e.g., microbes in the size range of 1-10 μm, is under development. Among other parts, its high-pressure valves and microfluidicacoustic traps have already been realized.For remote operation and upload of measurement data or images, or even live streaming of video, the submersible will betethered with a bi-directionally transmitting fiber optic cable, also capable of charging the onboard batteries for long missions.The one kilometer long fiber will be fitted within the hull, and by reeling out the fiber from the submersible, drag will be reduced.Herein, test results and images of the vehicle and its complete, and continuously developed, subsystems are presented.The vehicle, and its subsystems as stand-alone instruments, will enable the exploration of previously unreachable analogenvironments on Earth, vital to the field of astrobiology, and act as a forerunner to a submersible hydrobot that can explore icecoveredoceans elsewhere in our solar system.
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| 10. |
- Jonsson, Jonas, et al.
(författare)
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Miniaturized submersible for exploration of small aqueous environments
- 2011
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Ingår i: Oceans’11 MTS/IEEE Kona, Hilton Waikoloa Village, Kona, Hawai‘i September 19-22, 2011.
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Konferensbidrag (refereegranskat)abstract
- Remotely operated vehicles (ROVs) are commonlyused for sub-surface exploration. However, multi-functionalROVs tend to be fairly large, while preferred small and compactROVs suffer from limited functionality. The Deeper Access,Deeper Understanding (DADU) project aims to develop a smallsubmersible concept using miniaturization technologies to enablea high functionality. An operator is able to maneuver the vehiclewith five degrees of freedom using eight small thrusters, while aset of accelerometers and gyros monitor the orientation of thesubmersible. A single fiber optic cable will connect thesubmersible to a control station and enable simultaneous dataand command transfers. Rechargeable battery packs providepower to the submersibles subsystems during operation. Thesewill be rechargeable through the fiber connection. A forwardlooking camera is aided by a laser topography measurementsystem, where distances, sizes and shapes of objects in view canbe determined to within 0.5 cm. For murkier environments, orwhen a more extensive mapping of the surroundings is needed,the small high-frequency side-scanning sonar can be used.Salinity calculations of the water will be available throughmeasurements of the conductivity, temperature and depth.Samples of water and particles within it will be enabled through awater sampler with an enriching capability. Flow sensors will beable to measure the water movement around the submersible’shull. The submersible and its subsystems are under continuousdevelopment. The vehicle itself, and its subsystems as stand-aloneinstruments, will enable the exploration of previouslyunreachable submerged environments, such as the sub-glaciallakes found in Iceland and Antarctica, or other submerged smallenvironments, such as pipe and cave systems.
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| 11. |
- Malik, Amer, et al.
(författare)
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Modeling and analysis of a phase change material thermohydraulic membrane microactuator
- 2013
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 22:1, s. 186-194
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Tidskriftsartikel (refereegranskat)abstract
- Presented in this work, is a Finite Element Method (FEM)-based model for phase change material actuators, modeling the active material as a fluid as opposed to a solid. This enables the model to better conform to localized loads, as well as offering the opportunity to follow material movement in enclosed volumes. Modeling, simulation and analysis of an electrothermally activated paraffin microactuator has been conducted. The paraffin microactuator used for the analysis in the current study exploits the large volumetric expansion of paraffin upon melting, which combined with its low compressibility in the liquid state allows for high hydraulic pressures to be generated. The purpose of the study is to supply a geometry independent model of such a microactuator through the implementation of a fluid model rather than a solid model, which has been utilized in previous studies. Numerical simulations are conducted at different frequencies of the heating source and for different geometries of the microactuator. The results are compared with the empirical data obtained on a close to identical paraffin microactuator, which clearly show the advantages of a fluid model instead of a solid state approximation.
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| 12. |
- Ogden, Sam, 1979-, et al.
(författare)
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A Latchable High-pressure Composite Valve Actuator Combining Paraffin and a Low Melting Point Alloy
- 2011
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Ingår i: Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 2011 16th International, Beijing, China. ; , s. 474-477
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Konferensbidrag (refereegranskat)abstract
- This work presents a latchable valve microactuator for use in high-pressure environments, for instance deep-sea sampling in missions of long duration. Mounted on a minisubmersible, it can be used in confined spaces, earlier virtually unreachable. However, the device can be used in any high-pressure application where long open and/or closed times are required, and power supply is an issue. The actuator is fabricated using standard batch-processes as photochemical machining, wet etching and lithography. Focus of this work is on the endurance of the actuator to facilitate a bistable valve. The actuator managed to keep a deflected position for almost 50 hours at 1.8 MPa applied pressure, after which the experiment was aborted.
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| 13. |
- Ogden, Sam, 1979-, et al.
(författare)
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A latchable high-pressure thermohydraulic valve actuator
- 2012
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Ingår i: Sensors and Actuators A-Physical. - : Elsevier. - 0924-4247 .- 1873-3069. ; 188, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a latchable thermohydraulic microactuator for use in high-pressure valves, e.g. for oceanic sampling in missions of long duration. Mounted on a miniature submersible, it can be used in confined spaces to explore previously unreachable environments. However, the device can be used in any high-pressure application where long duration open and/or closed valve states are required, and power consumption is an issue. The actuator is fabricated using standard batch-processes as photochemical machining, wet etching and photolithography. The actuation and latching mechanisms are both thermohydraulic, using solid-to-liquid phase transition of paraffin for actuation and of a low melting point alloy for latching. Focus of this work is on the endurance of the actuator to facilitate a bistable valve. The actuator managed to keep a deflected position for almost 50 hours to the load equivalent to 1.8 MPa applied pressure, after which the experiment was aborted. No pressure dependence was discovered in the latching losses, i.e. the difference in deflection before and after the actuator is powered off. Furthermore, the effect of intermixing of paraffin and the low melting point alloy was evaluated.
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| 14. |
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| 15. |
- Ogden, Sam, 1979-, et al.
(författare)
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A Latchable Valve for High-Pressure Microfluidics
- 2010
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 19:2, s. 396-401
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the strongest yet latchable valve in subcubic-centimeter size for microfluidic applications is presented. The device has an integrated actuator cavity consisting of three segments filled with paraffin, each operated by a separate heater. At one of the segments, a membrane valve head is deflected by the expansion of the resistively melted paraffin to close against its valve seat. Different heating sequences provide a latched closed or opened valve. The maximum pressure before any leakage occurred was 2.5 MPa. The leak pressure is found to be progressively dependent on the clamping pressure applied. The valve has an opening and closing time of 7 and 1 s, respectively. At an applied pressure of 0.3 MPa, the closed valve needs to be reactivated every 100 min to remain leakage free, leading to an average power consumption of 4.5 mW.
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| 16. |
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| 17. |
- Ogden, Sam, 1979-, et al.
(författare)
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Fluid behavior of supercritical carbon dioxide with water in a double-Y-channel microfluidic chip
- 2014
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Ingår i: Microfluidics and Nanofluidics. - : Springer Science and Business Media LLC. - 1613-4982 .- 1613-4990. ; 17:6, s. 1105-1112
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Tidskriftsartikel (refereegranskat)abstract
- The use of supercritical carbon dioxide (scCO(2)) as an apolar solvent has been known for decades. It offers a greener approach than, e.g., hexane or chloroform, when such solvents are needed. The use of scCO(2) in microsystems, however, has only recently started to attract attention. In microfluidics, the flow characteristics need to be known to be able to successfully design such components and systems. As supercritical fluids exhibit the exciting combination of low viscosity, high density, and high diffusion rates, the fluidic behavior is not directly transferrable from aqueous systems. In this paper, three flow regimes in the scCO(2)-liquid water two-phase microfluidic system have been mapped. The effect of both total flow rate and relative flow rate on the flow regime is evaluated. Furthermore, the droplet dynamics at the bifurcating exit channel are analyzed at different flow rates. Due to the low viscosity of scCO(2), segmented flows were observed even at fairly high flow rates. Furthermore, the carbon dioxide droplet behavior exhibited a clear dependence on both flow rate and droplet length.
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| 18. |
- Ogden, Sam, 1979-, et al.
(författare)
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Fluid mechanics of supercritical carbon dioxide with water in a double-y-channel microfluidic chip
- 2013
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Ingår i: Micromechanics and microsystems europe.
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Konferensbidrag (refereegranskat)abstract
- In this paper, three flow regimes in thesupercritical carbon dioxide-water two-phase microfluidicsystem are mapped. The effect of both totalflow rate and relative flow rate on the flow regime isevaluated. Furthermore, the droplet dynamics at thebifurcating exit channel is analysed at different flowrates. The influence of the capillary number ondroplet splitting at the exit is also evaluated.
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| 19. |
- Ogden, Sam, 1979-
(författare)
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High-Pressure Microfluidics
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, some fundamentals and possible applications of high-pressure microfluidics have been explored. Furthermore, handling fluids at high pressures has been addressed, specifically by creating and characterizing strong microvalves and pumps.A variety of microstructuring techniques was used to realize these microfluidic devices, e.g., etching, lithography, and bonding. To be able to handle high pressures, the valves and pumps need to be strong. This necessitates a strong actuator material. In this thesis, the material of choice is paraffin wax.A new way of latching paraffin-actuated microvalves into either closed or open position has been developed, using the low thermal conductivity of paraffin to create large thermal gradients within a microactuator. This allows for long open and closed times without power consumption.In addition, three types of paraffin-actuated pumps are presented: A peristaltic high-pressure pump with integrated temperature control, a microdispensing pump with high repeatability, and a pump system with two pumps working with an offset to reduce flow irregularities. Furthermore, the fundamental behavior of paraffin as a microactuator material has been explored by finite element modeling.One possibility that arises with high-pressure microfluidics, is the utilization of supercritical fluids for different applications. The unique combination of material properties found in supercritical fluids yields them interesting applications in, e.g., extraction and cleaning. In an attempt to understand the microfluidic behavior of supercritical carbon dioxide, the two-phase flow, with liquid water as the second phase, in a microchannel has been studied and mapped with respect to both flow regime and droplet behavior at a bi-furcating outlet.
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| 20. |
- Ogden, Sam, 1979-, et al.
(författare)
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Latchable Valve for Microfluidic Sampling from a Miniature Submersible
- 2012
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Ingår i: Actuator. ; , s. 717-720
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Konferensbidrag (refereegranskat)abstract
- This work presents latchable high-pressure valves. Such valves are useful in a number of applications, e.g deep-sea sampling. Actuation and latching are achieved by using sequential melting and solidification of three connected paraffin-filled cavities, as well as a compliant valve seat. The valve seat design uses the applied back pressure to improve sealing, shown both in the valve’s endurance and burst pressure. The valves were evaluated by pressurizing them with both compressed air and water. At an applied hydrostatic back pressure kept above 2.1 MPa, the valve managed to stay closed without power consumption for 19 hours. The burst pressure was determined to 20 MPa when subjected to a hydrostatic pressure, and 5.6 MPa when subjected to a pneumatic pressure.
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| 21. |
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| 22. |
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| 23. |
- Ogden, Sam, 1979-, et al.
(författare)
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On-chip pump system for high-pressure microfluidic applications
- 2013
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Konferensbidrag (refereegranskat)abstract
- This paper presents a micropump system with four integrated paraffin actuated pumps: Two mobile phase pumps and two sample injector pumps. The mobile phase pumps are evaluated by their ability to deliver a stable, low-ripple flow to be used in chip-based high performance liquid chromatography. It is shown that the two mobile phase pumps can be driven in combined operation with an induced offset to significantly lower flow fluctuations.
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| 24. |
- Ogden, Sam, 1979-, et al.
(författare)
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Review on miniaturized paraffin phase change actuators, valves, and pumps
- 2014
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Ingår i: Microfluidics and Nanofluidics. - : Springer Science and Business Media LLC. - 1613-4982 .- 1613-4990. ; 17:1, s. 53-71
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Forskningsöversikt (refereegranskat)abstract
- During the last fifteen years, miniaturised paraffin actuation has evolved through the need of a simple actuation principle, still able to deliver large strokes and high actuation forces at small scales. This is achieved by the large and rather incompressible volume expansion associated with the solid-to-liquid phase transition of paraffin. The common approach has been to encapsulate the paraffin by a stiff surrounding that directs the volume expansion towards a flexible membrane, which deflects in a directed stroke. However, a number of alternative methods have also been used in the literature. The most common applications to this date have been switches, positioning actuators, and microfluidic valves and pumps. This review will treat the historical background, as well as the fundamentals in paraffin actuation, including material properties of paraffin. Besides reviewing the three major groups of paraffin actuator applications; actuators, valves, and pumps, the modelling done on paraffin actuation will be explored. Furthermore, a section focusing on fabrication of paraffin microactuators is also included. The review ends with conclusions and outlook of the field, identifying unexplored potential of paraffin actuation.
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| 25. |
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| 26. |
- Sharma, Guniana, et al.
(författare)
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High-pressure stainless steel active membrane microvalves
- 2011
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 21:7, s. 075010-
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Tidskriftsartikel (refereegranskat)abstract
- In this work, high-pressure membrane microvalves have been designed, manufactured andevaluated. The valves were able to withstand back-pressures of 200 bar with a response timeof less than 0.6 s. These stainless steel valves, manufactured with back-end batch production,utilize the large volume expansion coupled to the solid–liquid phase transition in paraffin wax.When membrane materials were evaluated, parylene coated stainless steel was found to be thebest choice as compared to polydimethylsiloxane and polyimide. Also, the influence of theorifice placement and diameter is included in this work. If the orifice is placed too close to therim of the membrane, the valve can stay sealed even after turning the power off, and the valvewill not open until the pressure in the system is released. The developed steel valves, evaluatedfor both water and air, provide excellent properties in terms of mechanical stability, ease offabrication, and low cost. Possible applications include sampling at high pressures, chemicalmicroreactors, high performance liquid chromatography, pneumatics, and hydraulics.
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| 27. |
- Svensson, Stefan, 1985-, et al.
(författare)
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High-Pressure Peristaltic Membrane Micropump With Temperature Control
- 2010
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 19:6, s. 1462-1469
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Tidskriftsartikel (refereegranskat)abstract
- A high-pressure peristaltic membrane micropump, which is capable of pumping against a back pressure of 150 bar, has been evaluated. The main focus was to maintain the flow characteristics also at high back pressures. The pump was manufactured by fusion bonding of parylene-coated stainless-steel stencils. A large-volume expansion connected to the solid-to-liquid phase transition in paraffin was used to move 10 µm stainless-steel membranes. The pump was evaluated by using two different driving schemes, a four-phase cycle and a six-phase cycle. With the six-phase cycle, a constant flow rate of 0.4 µL min-1 was achieved over an interval ranging from atmospheric pressure to 130 bar. At lower back pressures, the more energy efficient four-phase cycle achieved slightly higher flow rates than the six-phase cycle. However, it required higher driving voltage at high back pressures. Since the pump is thermally activated, a temperature sensor was integrated to control the melting and solidification of paraffin, implying capability of increasing the performance of the pump. With a thickness of only 1 mm as well as a simple and robust design, the micropump is well suited for integration in analytical systems. The high pressures managed are in the region needed for, e.g., high-performance liquid chromatography systems.
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| 28. |
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