| 1. |
- Khaji, Zahra, 1983-
(författare)
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Extending Microsystems to Very High Temperatures and Chemically Harsh Environments
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aiming at applications in space exploration as well as for monitoring natural hazards, this thesis focuses on understanding and overcoming the challenges of extending the applicability of microsystems to temperatures above 600°C as well as chemically harsh environments. Alumina and zirconia high-temperature co-fired ceramics (HTCC) with platinum as the conductor material, have in this thesis, been used to manufacture a wide range of high-temperature tolerant miniaturized sensors and actuators, including pressure and flow sensors, valves, a combustor, and liquid monopropellant microthrusters.Interfacing for high temperatures is challenging. One solution is to transfer the signal wirelessly. Here, therefor, wireless pressure sensors have been developed and characterized up to 1000°C.It is usually unwanted that material properties change with temperature, but by using smart designs, such changes can be exploited to sense physical properties as in the gas flow sensor presented, where the temperature-dependent electrical conductivity of zirconia has been utilized. In the same manner, various properties of platinum have been exploited to make temperature sensors, heaters and catalytic beds. By in-situ electroplating metals after sintering, even more capabilities were added, since many metals that do not tolerate HTCC processing can be added for additional functionality. An electroplated copper layer that was oxidized and used as an oxygen source in an alumina combustor intended for burning organic samples prior to sample analysis in a lab on a chip system, and a silver layer used as a catalyst in order to decompose hydrogen peroxide in a microthuster for spacecraft attitude control, are both examples that have been explored here.Ceramics are both high-temperature tolerant and chemically resistant, making them suitable for both thrusters and combustors. The corresponding applications benefit from miniaturization of them in terms of decreased mass, power consumption, integration potential, and reduced sample waste.Integrating many functions using as few materials as possible, is important when it comes to microsystems for harsh environments. This thesis has shown the high potential of co-fired ceramics in manufacturing microsystems for aggressive environments. However, interfacing is yet a major challenge to overcome.
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| 2. |
- Bodén, Roger, 1979-
(författare)
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Microactuators for Powerful Pumps
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When paraffin wax melts it exhibits a large, relatively incompressible volume expansion. This can be used in microactuators for strong and large displacements, a rare combination among actuators. Furthermore, paraffin is inexpensive, inert and environmentally friendly, as well as easily processed and actuated. Together, these properties give paraffin actuators great potential for use in both low-cost and high-performance applications.In microfluidics, the miniaturization of various analysis systems decreases the volumes of samples and reagents needed, as well as the analysis throughput time. Using on-chip micropumps increases the efficiency of the microfluidic system, but a challenge for such pumps is the high back-pressure associated with separation, filtration or narrower channels.The objective of this thesis is to increase the understanding of paraffin in microactuators, as well as to further explore its possibilities and limitations. The main application area has been on-chip micropumps.For low-cost applications, actuators, pumps and dispensers have been fabricated in plastics and then evaluated. The dispenser is intended for on-chip storage and dispensing of liquids in a lab-on-a-chip that could be used in, e.g., point-of-care testing (POCT).For high-performance applications, metallic actuators, pumps and dispensers have been accomplished. The micropump is the world’s strongest mechanical micropump in sub-cubic centimetre size, capable of pressures of above 5 MPa. Possible applications are strong microhydraulics, on-chip chromatography, or medical microdosage systems.A limitation of paraffin is the relatively slow thermal actuation. In this thesis the thermal properties have also been turned into an advantage: Directional solidification is used to accomplish multiple stable states of the actuator displacement, withheld without any power consumption.For the future, the high-pressure capability may be improved by new designs. Optimization of speed and power consumption can be made by further work on modelling as well as on drive and control of the heating.
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| 3. |
- Cruz, Javier, 1990-
(författare)
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Microfluidics for High-Pressure Inertial Focusing : Focusing, Separation and Concentration of Micro and Sub-micron Particles
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The birth of microsystems set the ground for technologies never imagined before, for it is not only the small size what characterizes the miniaturized systems, but unique phenomena arise in the micro scale. This thesis relates to one such unique phenomenon, inertial focusing, a phenomenon that occurs in microfluidic systems if very special conditions are met and that allows for fine manipulation of particles in fluid samples. This ability is key in a bigger picture: the analysis of complex fluids, where rare particles of interest may be present in very few numbers amongst a myriad of others, making the task difficult – if not impossible. A system exploiting inertial focusing allows, for instance, to focus, separate, isolate and concentrate such rare particles of interest, and even to transfer them to another fluid, thereby enabling/facilitating their detection and analysis. Examples of rare particles of interest in complex fluids are circulating tumor cells in blood, that give away the presence of cancer, extracellular vesicles also in blood, that contain biomarkers with physiological and pathological information about the patient, or bacteria in natural water, where the species present and their numbers are to be monitored for safety reasons and/or biological studies. This thesis covers the state of art physical principles behind the phenomenon and extends the understanding both in theory and applications. Specifically, the technology is extended to allow for manipulation of sub-micron particles, a range of interest as it comprises bacteria, viruses and organelles of eukaryotic cells. This was possible by an analysis of the balance of forces in play and by the integration of inertial focusing in high-pressure systems (up to 200 bar). In a second block, a very special line of inertial focusing is introduced and developed; inertial focusing in High Aspect Ratio Curved (HARC) microfluidics. These systems, engineered to rearrange the force field responsible for the particle manipulation, not only achieve excellent performances for focusing and concentration of particles, but also extreme resolution in their separation (mathematically unlimited; demonstrated experimentally for differences in size down to 80 nm). Perhaps more important than the performance, the systems are stable, intuitive and simpler to design, attributes that we hope will make the technology and its outstanding benefits more accessible to the community. With its remarkable performance, it would not come as a surprise if, in the near future, inertial focusing makes a strong impact on how analyses are performed nowadays and opens up for possibilities beyond the current state of the art.
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| 4. |
- Hillmering, Mikael, 1982-
(författare)
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Polymer microfluidic systems for samplepreparation for bacterial detection
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis, caused by blood stream infection, is a very serious health condition thatrequires immediate treatment using antibiotics to increase the chances for patientsurvival. A high prevalence of antibiotic resistance among infected patients requiresstrong and toxic antibiotics to ensure effective treatment. A rapid diagnostic devicefor detection of antibiotic resistance genes in pathogens in patient blood would enablean early change to accurate and less toxic antibiotics. Although there is a pressingneed for such devices, rapid diagnostic tests for sepsis do not yet exist.In this thesis, novel advances in microfabrication and lab-on-a-chip devices arepresented. The overall goal is to develop microfluidics and lab-on-a-chip systems forrapid sepsis diagnostics. To approach this goal, novel manufacturing techniques formicrofluidics systems and novel lab-on-a-chip devices for sample preparation havebeen developed.Two key problems for analysis of blood stream infection samples are that lowconcentrations of bacteria are typically present in the blood, and that separation ofbacteria from blood cells is difficult. To ensure that a sufficient amount of bacteria isextracted, large sample volumes need to be processed, and bacteria need to be isolatedwith high efficiency. In this thesis, a particle filter based on inertial microfluidicsenabling high processing flow rates and integration with up- and downstream processesis presented.Another important function for diagnostic lab-on-a-chip devices is DNA amplificationusing polymerase chain reaction (PCR). A common source of failure for PCRon-chip is the formation of bubbles during the analysis. In this thesis, a PCR-on-chipsystem with active degassing enabling fast bubble removal through a semipermeablemembrane is presented.Several novel microfabrication methods were developed. Novel fabrication techniquesusing the polymer PDMS that enable manufacturing of complex lab-on-a-chipdevices containing 3D fluidic networks and fragile structures are presented. Also,a mechanism leading to increased accuracy in photopatterning in thiol-enes, whichenables rapid prototyping of microfluidic devices, is described. Finally, a novel flexibleand gas-tight polymer formulation for microfabrication is presented: rubbery OSTE+.Together, the described achievements lead to improved manufacturing methodsand performances of lab-on-a-chip devices, and may facilitate future development ofdiagnostic devices.
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| 5. |
- Lekholm, Ville, 1976-
(författare)
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High-Temperature Microfluidics for Space Propulsion
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, microfabrication methods and tools for analysis of heated cold-gas microthrusters are presented, with the aim of improving their reliability and performance. Cold-gas thrusters operate by accelerating pressurized gas through a nozzle. These thruster systems are very straightforward in both design and operation, relying on little more than a pressurized tank, a valve, and a nozzle. This makes them suitable for miniaturization, enabling their use on very small spacecraft. However, an inherent drawback with cold-gas thrusters is their low propellant efficiency – in thrusters known as specific impulse, or Isp. This is compounded by the fact that when reducing length, the volume, e.g., that of the propellant tank, reduces with the cube of the length, meaning that the maximum amount of storable fuel reduces quickly. Hence, maximizing fuel efficiency is even more important in miniaturized systems. Still, because of their other advantages, they remain suitable for many missions. Schlieren imaging – a method of visualizing differences in refractive index – was used thrughout this thesis to visualize exhaust jets from microthrusters, and to find leaks in the components. It was found that effects of the processing of conventionally fabricated silicon nozzles, resulted in a misalignment of up to 3° from the intended thrust vector, increasing propellant consumption by up to 5%, and potentially causing unintended off-axis acceleration of the spacecraft. Schlieren imaging was also used to verify that the exhaust from thrusters fabricated with close to circular cross-sections was well behaved. These nozzles did not suffer from the previous misalignment issue, and the shape of the cross-section decreased viscous losses. For applications requiring higher temperatures, a microthruster nozzle with an integrated flow sensor was fabricated from tape cast yttria stabilized zirconia. The ceramic substrate enabled heater temperatures of the nozzle exceeding 1000 °C, resulting in an increase in Isp of 7.5%. Integration of a flow sensor allowed the elimination of couplings and reduced the number of interfaces, thereby reducing the overall risk of failure. Close integration of the sensor allowed moving the point of measurement closer to the nozzle, enabling improved reliability of the measurements of the propellant consumption. The temperature of the heater, in combination with the ion conductive properties of the substrate proved to be a limiting factor in this design. Two routes were explored to overcome these problems. One was to use the temperature dependence of the ion conductivity as a sensing principle, thereby demonstrating a completely new flow sensor principle, which results in better calibration, tighter integration, and 9 orders of magnitude stronger signal. The other was using hafnium oxide, or hafnia, as a structural material for high-temperature micro-electromechanical systems. This involved developing a recipe for casting hafnia ceramic powder, and determining the Young's modulus and thermal shock resistance of the cast samples, as well as studying the minimum feature size and maximum aspect ratio of cast microstructures.
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| 6. |
- 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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| 7. |
- Ramachandraiah, Harisha
(författare)
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Microfluidic based isolation of circulating tumor cells from whole blood for cancer diagnostics
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Detection of circulating tumor cells (CTC) in peripheral blood is indicative of early recognition of tumor progression and such an important biomarker for early diagnosis, staging, monitoring and prognosis of cancer. However, CTC are found in very low concentrations and reliable isolation of these rare cells is challenging. Microfluidics enables precise manipulation of fluids and cells and is ideal for cell sorting methods for clinical diagnostics. The thesis contributes towards the development of microfluidic based CTC isolation methods from peripheral blood. The methods are based on size and immunoaffinity. The first part of the thesis describes the phenomenon of inertial focusing for size based cell separation at high throughputs. In paper 1, we demonstrate continuous filtration of leukocytes from diluted blood, with an efficiency of 78% at a flow rate of 2.2ml/min. In the paper 2, separation of total and subpopulation of leukocytes with a purity of 86% for granulocytes and 91% for lymphocytes is demonstrated. Furthermore, cancer cells spiked into whole blood could be separated at a yield of 88%. Finally, in paper 3 and 4 we unravel parts of the unexplored elasto-inertial microfluidics and was utilized to precisely focus the cells, as part of an integrated optofluidic micro flow cytometer device, capable to simultaneously measure fluorescence and scattering of cells and particles at a rate of 2500 particles/sec (paper 4). Second part of the thesis focuses on acoustophoresis. In (paper 5), a multifunctional acoustic microdevice was developed for isolation of cancer cells from red blood cells with a separation efficiency of 92.4% and trapping efficiency of 93%. In (paper 6), microbubbles activated acoustic cell sorter was developed for affinity based cell separation. As a proof of principle, cancer cells in a suspension were separated at an efficiency of 75%. In the third part, using cellulose nano fibrils (paper 7), we demonstrate efficiently capture and release of cancer cells at a release efficiency of 95%. Finally, a novel, single step self-assembly of spider silk proteins is introduced inside microfluidic channels for effective capture of cancer cells with 85% capture efficiency and subsequent release of captured cells with 95% release efficiency (paper 8). The novel recombinant silk modified microfluidic device was validated using pancreatic cancer patients. In summary, we have developed different microfluidic based isolation technologies for the capture and characterization of CTC.
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| 8. |
- Sharma, Gunjana
(författare)
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Heterogeneous Technologies for Microfluidic Systems
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, conventional and unconventional technologies have been studied and combined in order to make heterogeneous microfluidics with potential advantages, especially in biological applications. Many conventional materials, like silicon, glass, thermoplastic polymers, polyimide and polydimethylsiloxane (PDMS) have been combined in building heterogeneous microfluidic devices or demonstrators. Aside from these materials, unconventional materials for microfluidics such as stainless steel and the fluoroelastomer Viton have been explored. The advantages of the heterogeneous technologies presented were demonstrated in several examples: (1) For instance, in cell biology, surface properties play an important role. Different functions were achieved by combining microengineering and surface modification. Two examples were made by depositing a Teflon-like film: a) a non-textured surface was made hydrophobic to allow higher pressures for cell migration studies and b) a surface textured by ion track technology was even made super-hydrophobic. (2) In microfluidics, microactuators used for fluid handling are important, e.g. in valves and pumps. Here, microactuators that can handle high-pressures were presented, which may allow miniaturization of high performance bioanalyses that until now have been restricted to larger instruments. (3) In some applications the elastomer PDMS cannot be used due to its high permeability and poor solvent resistivity. Viton can be a good replacement when elasticity is needed, like in the demonstrated paraffin actuated membrane.(4) Sensing of bio-molecules in aquatic solutions has potential in diagnostics on-site. A proof-of-principle demonstration of a potentially highly sensitive biosensor was made by integrating a robust solidly mounted resonator in a PDMS based microfluidic system. It is concluded that heterogeneous technologies are important for microfluidic systems like micro total analysis systems (µTAS) and lab-on-chip (LOC) devices.
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| 9. |
- Södergren, Simon, 1992-
(författare)
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Miniaturized fluid system for high-pressure analytics
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High-pressure chemistry can be used to determine the contents of blood or water samples and to discover new chemistries. However, working with chemistry at pressures of many tens, or even hundreds, of bars often requires expensive and stationary equipment, such as autoclaves or chromatographic systems like high-performance liquid chromatography (HPLC).Since the introduction of microfluidics in the '90s, researchers have attempted to develop microfluidic chips as microreactors to speed up synthesis with faster mass and heat transfer. Other researchers have made efforts to create microfluidic chip-based HPLC to reduce the cost, increase the separation quality, speed up the analysis, and even enable portable systems for on-site medical or environmental analysis. Still, fully integrated systems have not yet been realized due to a lack of fluidic control components.This thesis presents novel methods for on-chip regulation and monitoring of pressure, flow, and temperature. Papers I and II specifically suggest a method for regulating backpressure and stabilizing pressure and flows using thermally controlled restrictors. Furthermore, a collaboration was made where a pressure-regulating chip was connected to an on-chip HPLC. The purpose of this was to activate sample plugs and therefore reduce the requirement for expensive surrounding equipment and enable portability, Paper III. Paper IV explores the use of a pressurized capsule to generate high-pressure flows that are coupled to a pressure-regulating chip to stabilize and regulate the pressure. Finally, an approach for integrating pressure sensors into high-pressure tolerant microchannels has been proposed, Paper V.The work conducted has provided new insights into fluid dynamics. The regulating method employed in Paper I-IV utilizes a restrictor that alters the pressure drop as temperature changes, hence changing the viscosity of the fluid. Although this technology has been known since before, new understandings have emerged regarding how the compressibility of incompressible fluids must be considered at higher pressures. Additionally, the concept of buffer capacitance is presented, which is central when working with high-pressure microfluidics.Through this thesis, discoveries of high-pressure microfluidics have been accomplished, which enable micro-total-analysis systems that could serve as portable HPLC equipment.
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| 10. |
- Gunnarsson Sarius, Niklas, 1976-
(författare)
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Surface Technology for Optical and Electrical Connectors
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis treats surface engineering with the purpose of improved quality of optical and electricalconnectors with a focus on electroplated and magnetron sputtered materials. In electroforming of tools formanufacturing optical connectors, the influence of ultrasonic agitation on intrinsic stresses and fillingproperties of electroplated Ni has been studied. It is established that the ultrasonic agitation at the substratesurface during deposition impacts the intrinsic stresses making it possible to increase deposition rate viacurrent density, with stress-free or low-stress levels in the Ni layers. Reduced variations of the intrinsicstress over the surface with the current density is a further important result. Filling of grooves byelectroplating of Ni using ultrasonic agitation is demonstrated. This is due to increasing mass transport ofspecies into the grooves compared to conventional pumped agitation. The enhanced filling propertiesmakes it possible to electroplate Ni in the bottom of high-aspect-ratio grooves. In order to industriallyimplement new nanocomposite coatings on electronic connectors, studies have been performed regardingthe thermal diffusion barrier properties against Cu for Ti-Si-C and Ti-Si-C-Ag nanocomposites, depositeddirectly onto Cu substrates or with sputtered Ni, Ti or electroplated Ni as an intermediate coating. Theapplication of an electroplated Ni diffusion barrier coating, hinders Cu from reaching the surface of thenanocomposites. Also, Ti-Si-C-Ag nanocomposite deposited on magnetron sputtered Ni or Ti on Cusubstrates hinder Cu from diffusing to the surface after annealing. The contact resistance of Ag-Pdtopcoated Ti-Si-C-Ag-Pd and Ti-Si-C-Ag nanocomposite coatings in contact with hard gold is shown tocompete with hard gold in contact with itself, as electrical contact coatings at contact forces around 5 N.Ag-Pd topcoated Ti-Si-C-Ag-Pd in contact with hard gold is shown to have approximately the same contactresistance as hard gold in contact with hard gold at contact forces around 0.1 N, which here is in the 10 mΩrange, while Ti-Si-C-Ag nanocomposite coatings in contact with hard gold has a contact resistance that isup to 10 times higher. The overall contribution of this thesis can be summarised as a deeper knowledge andunderstanding of techniques and coatings, that help reduce cost and increase reliability of electronics.
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