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Resumen de Lab on a chip systems for biochemical analysis, biology and synthesis: towards simple, scalable microfabrication technologies based on COC and LTCC /

Miguel Berenguel Alonso

  • Lab on a Chip (LOC) technology has experienced a remarkable growth in the last two decades, owing to the development of novel microfabrication technologies and the better understanding of physical phenomena at the microscale. LOC systems present several advantages over conventional macroscopic systems: enhanced mass and energy transport, miniaturization, automation, integration and throughput, among others. These advantages have drawn the attention of a wide scientific and technological community, related to very different application areas such as chemistry, biology, medicine and nanotechnology.

    However, the field is still in a development stage, as proven by the limited number of LOC products in the market. Different challenges need to be addressed to overcome this issue. On the one hand, the LOC system should integrate all the required operations for a given application, while keeping a simple interface for the end-users. Moreover, LOC systems should significantly outperform existing macroscopic analogues in order to justify the required investment in a new technology. On the other hand, materials and fabrication technologies need to provide the means to achieve that, both at a prototyping and mass production levels. Therefore, the scalability of the fabrication process should also be considered in order to bridge the gap between research prototyping and commercial production.

    This dissertation is focused on the development of LOC devices using scalable processes based on multilayer fabrication approaches. These LOC systems are targeted at very different applications, examples of how different fields can benefit from this technology. The specific requirements of each application have driven the selection of the substrate and the integration of the necessary elements on the LOC systems.

    The first case consists on the development of a LOC device using Cyclic Olefin Co-polymer (COC) as substrate and a simple magnetic actuator for the control and actuation of Magnetic Beads on-chip. This analytical system was devoted to the detection of pathogenic E.~coli O157:H7 whole cells, demonstrating an enhanced performance and simple operation. The second example is also based on a COC device, in this case, to trap and culture oocyte cells. This LOC system demonstrated its suitability for Assisted Reproductive Technology applications. Moreover, the integration of transparent heaters lays the grounds for a fully independent culture/fertilization platform. In both cases, COC provides significant advantages such as high transparency, low autofluorescence and biocompatibility.

    The last case consists on the development of Low Temperature Co-fired Ceramics (LTCC) microreactors for the synthetic process intensification of nanomaterials designed for analytical applications. This substrate and its associated fabrication technology enabled the monolithic integration of heaters, complex 3D-structures and optical windows. Magnetite nanoparticles and Carbon Dots were synthesized under harsh reaction conditions, taking advantage of the chemical and structural stability of the LTCC substrate.

    The results presented in this dissertation demonstrate the versatility of LOC technology and the advantages that it provides in a wide range of applications. Moreover, the fabrication methodologies developed could potentially be extrapolated to a mass production scale, which is of paramount importance for the technology transfer to commercial and industrial applications.


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