Pouya Mehrdel

Over the past decade, microfluidic technology has proven its capabilities to start bringing detection and quantification capacities to novel miniaturized devices. The current generation of microfluidic platforms provide great precision in detection and quantification. At the same time, they have started to evolve towards self-sufficient (stand-alone) setups. These platforms are relying less and less on external power sources and they use built-in detection and quantification methods to be flexible and mobile. Among the various Lab on a Chip (LOC) applications, micro–Total Analysis Systems (µTAS) and Point of Care Tests (POCT) are the pinnacles of microfluidic platforms. They are accurate, rapid, cost-effective, and user-friendly. They can monitor and measure compounds that were, previously, only detectable in state-of-the-art laboratories. This characteristic is quite important and vital, especially when it comes to human health status monitoring. Therefore, developing POCs and µTASs has been the center of attention for researchers in recent years. To reduce the reliance of microfluidic platforms on external power sources and measuring instruments. There is the need to improve and enhance the microfluidic platforms, not only from the performance point-of-view but also from their manufacturability, to be able to batch produce them at lower costs. Most microfluidic circuits detect or measure a compound and in the first step, they need to label/enhance a reaction, in other words, mix two or more components and then analyze the results based on the readout. This thesis proposes an enhancement of the performance of a key element in most µTAS and POC devices such as the micromixer, with the introduction of a geometrical expansion that increases the diffusion path without increasing the pressure loss. Afterwards, its performance is validated and the design has been used to quantify for the first time on a microfluidic platform the ionic strength of buffered and non-buffered solutions. Finally, and to avoid the need for syringe pumps, in the same quantification strategy, we have introduced paper as a substrate material and optimized the inlet geometry to enhance the performance of the novel microfluidic paper-diffusion-based sensor for ionic strength quantification. The proposed sensor was able to quantify the ionic strength of buffered and non-buffered solutions down to 0.1 M concentrations using Whatman 5 paper substrate. Durante la última década, la tecnología microfluídica ha demostrado sus capacidades para empezar a aportar capacidades de detección y cuantificación a nuevos dispositivos miniaturizados. La generación actual de plataformas microfluídicas proporciona una gran precisión en la detección y cuantificación. Al mismo tiempo, han comenzado a evolucionar hacia configuraciones autosuficientes (independientes). Estas plataformas dependen cada vez menos de fuentes de alimentación externas y utilizan métodos de detección y cuantificación integrados para ser flexibles y móviles. Entre las diversas aplicaciones de Lab on a Chip (LOC), los sistemas de análisis micro-total (µTAS) y las pruebas de punto de cuidados (POCT) son los pináculos de las plataformas microfluídicas. Son precisas, rápidas, rentables y fáciles de usar. Pueden monitorizar y medir compuestos que anteriormente sólo eran detectables en laboratorios de última generación. Esta característica es muy importante y vital, especialmente cuando se trata de la vigilancia del estado de salud humana. Por lo tanto, el desarrollo de POCs y µTASs ha sido el centro de atención para los investigadores en los últimos años. Reducir la dependencia de las plataformas microfluídicas de fuentes de energía externas e instrumentos de medición. Existe la necesidad de mejorar y mejorar las plataformas microfluídicas, no sólo desde el punto de vista del rendimiento, sino también desde su viabilidad de fabricación, para poder fabricarlas por lotes a menores costes. La mayoría de los circuitos microfluídicos detectan o miden un compuesto y, en el primer paso, necesitan etiquetar/mejorar una reacción, es decir, mezclar dos o más componentes y luego analizar los resultados basándose en la lectura. Esta tesis propone una mejora del rendimiento de un elemento clave en la mayoría de los dispositivos µTAS y POC como el micromegador, con la introducción de una expansión geométrica que aumenta la trayectoria de difusión sin aumentar la pérdida de presión. Posteriormente, se valida su rendimiento y se utiliza el diseño para cuantificar por primera vez en una plataforma microfluídica la fuerza iónica de las soluciones tamponadas y no tamponadas. Por último, y para evitar la necesidad de bombas de jeringa, en la misma estrategia de cuantificación, hemos introducido el papel como material sustrato y optimizado la geometría de entrada para mejorar el rendimiento del novedoso sensor microfluídico basado en difusión de papel para la cuantificación de la fuerza iónica. El sensor propuesto fue capaz de cuantificar la resistencia iónica de las soluciones tamponadas y no tamponadas hasta concentraciones de 0,1 M utilizando el sustrato de papel Whatman 5.

Microfluidic paper-based analytical devices (µPADs) are leading the field of low-cost, quantitative in-situ assays. However, understanding the flow behavior in cellulose-based membranes to achieve an accurate and rapid response has remained a challenge. Previous studies focused on commercial filter papers, and one of their problems was the time required to perform the test. This work studies the effect of different cellulose substrates on diffusion-based sensor performance. A diffusion-based sensor was laser cut on different cellulose fibers (Whatman and lab-made Sisal papers) with different structure characteristics, such as basis weight, density, pore size, fiber diameter, and length. Better sensitivity and faster response are found in papers with bigger pore sizes and lower basis weights. The designed sensor has been successfully used to quantify the ionic concentration of commercial wines with a 13.6 mM limit of detection in 30 s. The developed µPAD can be used in quantitative assays for agri-food applications without the need for any external equipment or trained personnel.

Microfluidic paper-based analytical devices (µPADs) are a promising technology to enable accurate and quantitative in situ assays. Paper’s inherent hydrophilicity drives the fluids without the need for external pressure sources. However, controlling the flow in the porous medium has remained a challenge. This study addresses this problem from the nature of the paper substrate and its design. A computational fluid dynamic model has been developed, which couples the characteristics of the porous media (fiber length, fiber diameter and porosity) to the fluidic performance of the diffusion-based µPAD sensor. The numerical results showed that for a given porous membrane, the diffusion, and therefore the sensor performance is affected not only by the substrate nature but also by the inlets’ orientation. Given a porous substrate, the optimum performance is achieved by the lowest inlets’ angle. A diffusion-based self-referencing colorimetric sensor was built and validated according to the design. The device is able to quantify the hydronium concentration in wines by comparison to 0.1–1.0 M tartaric acid solutions with a 41.3 mM limit of detection. This research showed that by proper adjustments even the simplest µPADs can be used in quantitative assays for agri-food applications.

Blood plasma separation from undiluted blood is an essential step in many diagnostic procedures. This study focuses on the numerical optimization of the microfluidic blood plasma separator (BPS) and experimental validation of the results to achieve portable blood plasma separation with high purity and reasonable yield. The proposed design has two parts: a microchannel for blood processing and a tank below the aforementioned main channel for plasma collection. The study uses 3D computational fluid dynamic analysis to investigate the optimal ratio of heights between the top microchannel and the tank and their geometry at various flow rates. Thereafter, the results are compared with the experimental findings of the fabricated devices. These results are contrasted with some recent reported works to verify the proposed device’s contribution to the improvement in the quality and quantity of the extracted plasma. The optimized design is capable of achieving a 19% yield with purity of 77.1%, depending on the requirement of the point-of-care (POC) application. These amounts could be tuned, for instance to 100% pure plasma, but the yield would decrease to 9%. In this study, the candidate application is hemostasis; therefore, the BPS is integrated to a biomimetic surface for hemostasis evaluation near the patients.

Micro Electro Mechanical Systems (MEMS) and microfluidic devices have found numerous applications in the industrial sector. However, they require a fast, cost-effective and reliable manufacturing process in order to compete with conventional methods. Particularly, at the sub-micron scale, the manufacturing of devices are limited by the dimensional complexity. A proper bonding and stiction prevention of these sub-micron channels are two of the main challenges faced during the fabrication process of low aspect ratio channels. Especially, in the case of using flexible materials such as polydimethylsiloxane (PDMS). This study presents a direct laser microfabrication method of sub-micron channels using an infrared (IR) ultrashort pulse (femtosecond), capable of manufacturing extremely low aspect ratio channels. These microchannels are manufactured and tested varying their depth from 0.5 μ m to 2 μ m and width of 15, 20, 25, and 30 μ m. The roughness of each pattern was measured by an interferometric microscope. Additionally, the static contact angle of each depth was studied to evaluate the influence of femtosecond laser fabrication method on the wettability of the glass substrate. PDMS, which is a biocompatible polymer, was used to provide a watertight property to the sub-micron channels and also to assist the assembly of external microfluidic hose connections. A 750 nm depth watertight channel was built using this methodology and successfully used as a blood plasma separator (BPS). The device was able to achieve 100% pure plasma without stiction of the PDMS layer to the sub-micron channel within an adequate time. This method provides a novel manufacturing approach useful for various applications such as point-of-care devices.

A passive portable microfluidic blood–plasma separator for simultaneous determination of direct and indirect ABO/Rh blood typing.

A novel type of spiral micromixer with expansion and contraction parts is presented in order to enhance the mixing quality in the low Reynolds number regimes for point-of-care tests (POCT). Three classes of micromixers with different numbers of loops and modified geometries were studied. Numerical simulation was performed to study the flow behavior and mixing performance solving the steady-state Navier–Stokes and the convection-diffusion equations in the Reynolds range of 0.1–10.0. Comparisons between the mixers with and without expansion parts were made to illustrate the effect of disturbing the streamlines on the mixing performance. Image analysis of the mixing results from fabricated micromixers was used to verify the results of the simulations. Since the proposed mixer provides up to 92% of homogeneity at Re 1.0, generating 442 Pa of pressure drop, this mixer makes a suitable candidate for research in the POCT field.

A novel single-layer passive mixer is designed which takes advantage of gradually increasing the radius of curvature of a spiral micro mixer.

Blood typing is especially important in any emergency transfusion and during pregnancy.