Resumen de Diseño de dispositivos lab-on-a-chip para separaciones magnetoforéticas
- español
En las últimas décadas, el uso de micro- y nanomateriales magnéticos ha crecido exponencialmente debido a sus excelentes propiedades en comparación con sus equivalentes macroscópicos. Aunque las aplicaciones lab-on-a-chip más recientes han puesto de manifiesto su papel prometedor en el desarrollo de procesos bioquímicos rápidos y eficientes, la manipulación magnética de los mismos se ha explorado en menor medida, especialmente en la microescala. Por lo tanto, se requiere el desarrollo de herramientas innovadoras que permitan el diseño racional de las etapas de separación con las que se facilite la integración de estas tecnologías tan atractivas.
En la presente tesis doctoral se desarrollan nuevos enfoques teóricos para la descripción de varios dispositivos magnetoforéticos, en los que se integran distintos materiales. Se describen los fundamentos de las separaciones magnéticas para establecer los antecedentes teóricos básicos para comprender el funcionamiento de dichos sistemas. Los modelos se desarrollan teniendo en cuenta las fuerzas dominantes que intervienen en la separación. Posteriormente, los modelos se utilizan para analizar distintos dispositivos de flujo continuo empleados en diferentes aplicaciones.
Se considera que en esta tesis doctoral se proporcionan herramientas útiles, precisas y de bajo coste computacional para el diseño de un gran número de aplicaciones lab-on-a-chip. Además, se proponen directrices para el desarrollo de dispositivos magnetoforéticos eficientes, en los que se pueden integrar tanto partículas sólidas como ferrofluidos. Debido a las propiedades ventajosas de estos materiales, así como a las excepcionales características de la microfluídica, este estudio puede resultar clave en el desarrollo futuro e integración de estas innovadoras tecnologías.
- English
The use of micro- and nanomaterials with magnetic properties has exponentially grown in the last few decades as a consequence of their superior properties in comparison to their bulk counterparts. Although novel lab-on-a-chip applications have shown the promising role of these materials in the development of fast and efficient biochemical processes, their safe and reliable manipulation with magnetic fields is less explored, especially at the microscale. Thus, the development of innovative tools is required in order to enable the rational design of novel separation steps which will facilitate the successful integration of these attractive technologies.
In this doctoral dissertation, novel theoretical approaches are developed for the detailed description of different magnetophoretic devices in which different fluid and solid magnetic materials are integrated. First, the principles of magnetic separations are reviewed in order to establish the basic theoretical background. Second, the models to describe magnetophoresis are developed. These take into account the dominant magnetic and hydrodynamic forces acting on the materials as well as coupled material-fluid interactions. For all the models, the governing equations of fluid flow and mass transfer are solved numerically, while the magnetic force generated by different permanent magnets is predicted using analytical methods. The models are later applied for the analysis of continuous-flow magnetophoretic devices designed for different applications.
The first application involves the separation of magnetic beads from blood for the development of continuous extracorporeal detoxification processes. For this analysis, three different Eulerian-Lagrangian approaches are developed to study both particle separation from flowing blood streams and fluid-particle interactions that might compromise the integrity of the biofluid during the process. The models are evaluated in terms of computational cost and accuracy, and a screening process is carried out in order to find the best alternative. The selected model was validated via application to a prototype device which was experimentally characterized using fluorescence microscopy. The impact of different process variables and parameters – flowrates, bead and magnet dimensions and the rheological properties of the fluids – was theoretically and experimentally quantified. The optimized conditions were finally applied to recover the particles from human whole blood without causing blood loss or dilution, and the experimental results were found to match the theoretical predictions, showing the capability of this model to accurately describe magnetophoresis from complex fluids such as blood. The second application addressed in this dissertation covers the generation of ferrofluid droplets and their later magnetic deflection across multilaminar flows for the continuous assembly of polyelectrolyte capsules. Droplet generation was modeled with the Volume of Fluid method, including the surface tension forces in the model; droplet deflection was studied within a Eulerian-Lagrangian framework to optimize the required processing power to run the simulations. After studying a broad range of magnetic field conditions and a wide flow rate ranges for the multiple fluidic phases involved in the process, the optimum conditions obtained with the model for achieving deflection without perturbing the flow coincided with the experimental findings. Finally, the proof of concept for the continuous-flow synthesis of polyelectrolyte capsules was demonstrated in a revolutionary “Snakes-and-Ladders” chip design, achieving a significant reduction in processing times when compared to the conventional method.
Concluding, it is considered that the numerical approaches developed in this doctoral dissertation are accurate, computationally inexpensive and useful tools for the design of a high number of lab-on-a-chip applications. In addition, different guidelines have been proposed for the development of efficient magnetophoretic devices in which both solid particles and ferrofluids can be integrated into. Due to the advantageous properties of these materials along with the outstanding features of microfluidics, this dissertation could be key for facilitating the future development and establishment of these novel technologies.
